Podcasts about AAV

We're speculating about whether short-term, high AAV contracts are becoming the new norm in MLB. -Elly Turns Down Record Contract -Mookie Will Retire After 2032 -Verlander's Next Team -HOF Reveal Tuesday -Jayhay's Bichette Takes -Sal Frelick Tomorrow! Use promo code “Jared” to get up to $1000 in bonus credits AND a special pick on Underdog! PLAY HERE: https://play.underdogfantasy.com/pc-d2PyPbHAPu 0:00 - Trying New Food 10:10 - NFL Playoffs 14:35 - Reds / Elly Offer 22:00 - New CBA 25:15 - Guess That Player 37:02 - Betts Retirement 40:00 - Tide Shift 47:00 - Verlander Interest 1:00:35 - HOF Reveal 1:12:37 - Jayhay Nuggs 1:13:30 - Final Thoughts Learn more about your ad choices. Visit megaphone.fm/adchoices

Segment 1 – News and Notes1.    The Dodgers made a splash by signing Kyle Tucker to the largest AAV in history – 4 years and $240 million with opt-outs after 2027 and 2028.8.a.    A lot of people are upset about the dominance of the Dodgers.  “They are ruining baseball!”  What say you?b.    Were you surprised that Tucker signed a shorter deal but for more money?c.    The odd thing is that he's not even the best player on the team, maybe not even the top 3 players on the team.d.    I don't see any playing time loss for anyone with the exception of a potential delay in the arrival of Josue DePaula or Zyhir Hope.  Do you see anything?2.    The Mets were spurned by Tucker and pivoted to Bo Bichette, signing him to a massive three-year, $126 million deal with a unique opt-out clause.  He can opt out after each year, and if he does, the Mets have to pay him a $5 million bonus. a.    $42 million a year for Bichette?  Thoughts on the signing?b.    He'll likely play third base.  Who sits out of Baty or Vientos?c.    Also, I think Jett Williams needs to learn the outfield, plus, with the Mets not getting Tucker, Benge is still safe – for now.  Thoughts?3.    A small but interesting, three-way trade was pulled off by the Angles, Rays and Reds.  The Rays sent Josh Lowe to the Angels and Gavin Lux to the Rays, with the Reds acting as the intermediary. The Angels shipped RHP Chris Clark to Tampa Bay and LHP Brock Burke to Cincinnati.a.    Who's value goes up more?  Lowe, Lux, or neither?b.    Does this open a chance for Jacob Melton in Tampa?c.    Will Lux ever be more than an afterthought?Segment 2 – Third Base Rankings for the 2026 Season1.    How are you approaching this position for your upcoming drafts?2.    We will break down the top 15 to 20 in detail.  Then, go through 20 to 30 in less detail.  We will end by jumping around the remaining ranked players.3.    Which player not in the Top 10 has a chance to emerge there next season?4.    Which Top 10 player will not be there next season?5.    Give me a couple of sleepers6.    Give me one, maybe two guys you are just going to avoid drafting?

Evan unloads a full conspiracy theory: Rob Manfred is not mad about the Dodgers dominating baseball, he's thrilled. The idea is simple and terrifying. Let the Dodgers keep stacking stars, let fans scream “baseball is broken,” and then use that outrage to win the PR war for a salary cap the players will hate. Tiki buys it immediately, even as they admit it still might never work. From there, the focus snaps back to the Mets problem that keeps getting louder: they can “try” for Tucker, but where's the backup plan? A caller compares Cashman's quick Soto pivot to the Mets dragging their feet, and the guys dig into the bigger issue: Stearns will spend huge AAV, but refuses to go long term, which kills half the market. Then it turns into pure show chaos: Free Agent Bingo standings, Knicks misery, and Mets fans roasting the offseason, including a fake “Mets fan” troll call and the return of the “chomping at the bit” debate right before Evan teases a pivot plan that does not include Cody Bellinger.

The show comes to a screeching halt with legitimate breaking news as the Mets land Bo Bichette on a three-year, $126 million deal, and Evan immediately reminds everyone he called the pivot before it happened. Evan and Tiki react in real time to the signing, the massive AAV, the opt-out structure, and what this move says about how David Stearns is operating in the market. They break down where Bichette fits defensively, why third base appears to be the early plan, and how much offensive ground this actually recovers after losing Pete Alonso and Kyle Tucker. The guys debate the risk of one-year and two-year opt outs, the surprising draft pick cost, and whether this is a necessary concession in today's marketplace. Plus, what this move means for Philadelphia after reportedly agreeing to a long-term deal, how Toronto now pivots, why Cody Bellinger still does not make sense for the Mets, and whether this finally changes the tone of a chaotic Mets offseason. Live calls, instant reactions, and a full breakdown of how the roster and expectations shift after the biggest move yet.

With Kyle Tucker off the board, the Mets are staring into the void and Evan lays out why Cody Bellinger is not a realistic “panic buy,” even with rumors of the Yankees sitting around five years and $160M. If the Mets wouldn't go long for Tucker or Alonso, why would they suddenly cave to Scott Boras? Then the debate turns into the uncomfortable part: what's the actual pivot? Evan pitches a wild, short-term, mega-AAV idea for Bo Bichette that's basically a Tucker-style offer to blow him away, get an opt-out, and take another swing at free agency before 30. The problem: where does he play, and how much run prevention are you willing to sacrifice to get a real bat? Tiki pushes back on the defensive domino effect, the “versatility” trap, and the weekly second-guessing Mets fans would live through. The guys kick around the alternatives (including a one-year Eugenio Suárez power play), plus why pitching still has to be the priority no matter what. And of course, the segment ends with the same challenge: if you hate the plan, tell us a better one.

Episode 132 of Tablesetters is an emergency reaction pod centered on a market-shifting decision, as Kyle Tucker agrees to a four-year, $240 million deal with the Los Angeles Dodgers, immediately resetting both the top of the free-agent market and the competitive landscape heading into 2026. We open with the deal itself, breaking down how a $60 million AAV contract represents a decisive pivot away from traditional long-term free-agent structures and toward compressed risk at the very top of the market. We discuss why Tucker and the Dodgers were uniquely aligned on this structure, how Los Angeles leveraged competitive certainty and roster context over sheer length, and what this agreement signals about where elite player negotiations may be heading. From there, we examine the broader market fallout. Tucker's decision effectively closes the door on the Mets' reported $50 million-per-year short-term push and the Blue Jays' long-term pursuit, while clarifying how teams are increasingly being forced to choose between flexibility and security. We explore how this signing reshapes leverage for remaining free agents and how quickly the rest of the offseason could now accelerate. We then turn to the on-field implications in Los Angeles. Tucker's arrival addresses a clear offensive inefficiency in the Dodgers' outfield, particularly in on-base ability, while raising both the floor and ceiling of a lineup already built to contend. We break down the inevitable roster ripple effects, including the pressure this puts on depth pieces and the difficult decisions that follow when a true superstar enters the mix. Finally, we zoom out to the long view. We discuss the draft and development costs attached to signing another qualifying-offer free agent, why the Dodgers were willing to absorb them, and how this move fits within an organization balancing immediate championship windows with a steady pipeline of young talent nearing the majors. Steve and Devin connect the dots between financial creativity, competitive leverage, and roster timing, framing the Tucker signing as more than a splash — it is a signal about how the next phase of team building at the top of the sport may look. ⚾️ An emergency decision, a market reset, and a defining move of the offseason.

Episode 133 of Tablesetters is a live, solo emergency reaction to the New York Mets signing Bo Bichette to a three-year, $126 million contract, a deal that immediately reframes the Mets' offseason after missing on Kyle Tucker. This episode focuses on why this was not a fallback move. We break down the structure of the contract, the $42 million AAV, the opt-outs, and the absence of deferrals, and explain how it mirrors the same short-term, high-value philosophy the Mets pursued with Tucker. The player changed. The strategy did not. We also examine the market context that sharpened the decision. According to Bob Nightengale, the Philadelphia Phillies believed they had Bichette locked up on a seven-year, $200 million deal before the Mets stepped in. Rather than matching length and risk, New York leveraged annual value and optionality, reshaping both the division and the market in the process. From there, we dig into what the Mets are actually buying on the field, how Bichette's 2025 season reestablished his offensive ceiling, and why the club appears comfortable with the defensive trade-offs at third base given their infield alignment and roster depth. This is not a full teardown. It's a focused reaction on leverage, roster timing, and what this move says about how the Mets are choosing to compete right now. ⚾️ A fast pivot, a clear philosophy, and another defining contract in a rapidly evolving offseason.

Episode 131 of Tablesetters is a reaction pod focused on a pivotal stretch of the offseason, as a major pitching commitment in Boston, a franchise-defining signing in Chicago, a stalled superstar market, and a rare ballpark adjustment collectively show how teams are adapting to risk, scarcity, and roster timing heading into 2026. We open in Boston, where the Red Sox are set to sign left-handed pitcher Ranger Suárez to a five-year, $130 million contract with no deferrals, no opt-outs, and no no-trade protection. The deal represents the largest free-agent commitment of Craig Breslow's tenure and a clear pivot back toward rotation strength after Boston stalled in its pursuit of an infield upgrade. Suárez joins a rotation led by Garrett Crochet and recently bolstered by Sonny Gray and Johan Oviedo, signaling a belief in run prevention, depth, and managed workloads over chasing innings volume. From there, we shift to Chicago, where the Cubs make the biggest offensive splash of their offseason by signing Alex Bregman to a five-year, $175 million deal with significant deferrals. We break down why this move reshapes the Cubs' lineup, how it reflects a philosophical shift from the Ricketts family, and what Bregman's arrival means for the infield picture alongside Dansby Swanson, Nico Hoerner, and Matt Shaw as Chicago pushes firmly into a win-now posture. Next, we zoom out to the top of the free-agent market, where Kyle Tucker remains unsigned. We discuss reports that the Mets have offered a short-term deal with a $50 million average annual value, while the Blue Jays have made a long-term offer, highlighting the growing divide between extreme AAV flexibility and traditional long-term guarantees — and why Tucker's decision could reshape the rest of the offseason. We close in Kansas City, where the Royals announce changes to the outfield dimensions at Kauffman Stadium, moving in the fences in both corners and the alleys while lowering wall height. We explore why this calculated adjustment is aimed at boosting offense without compromising pitching, how it aligns with the Royals' left-handed core, and what it says about teams looking for marginal gains beyond the roster itself. Steve and Devin connect the dots between market behavior, roster construction, financial flexibility, and environment, focusing on how these moves reflect a league increasingly split between certainty, creativity, and controlled risk. ⚾️ One week, four signals, and a clearer picture of how contenders are being built.

The Mets offseason is at a tipping point, and Kyle Tucker is the one move that could change the entire mood. Evan and Tiki debate why Tucker would “save” the winter, why the Mets' only real edge is money, and how David Stearns' short-term, high-AAV philosophy is shaping everything after losing Pete Alonso. Then it turns into a wild New York sports morning: John Harbaugh meets with the Giants, fans call in on Tucker vs pitching help (Suarez, Valdez, Giolito), and the guys hit the Yankees' under-the-radar Ryan Weathers trade before circling back to the big question: who's the Mets ace right now? Chapters 00:00 Kyle Tucker “saves” the Mets offseason 03:20 Mets vs Dodgers vs Blue Jays and what actually matters 06:25 Trusting Stearns, roster “maybes,” and the first base frustration 14:00 Giants news: John Harbaugh meeting and the Tisch plane buzz 18:30 Calls: Tucker vs Suarez/Valdez, plus the rotation anxiety 35:15 Yankees add Ryan Weathers, then Giolito and the Mets “ace” debate

Evan and Tiki open the phones and Mets fans go straight to the big question: if you can only make one marquee move, is it Kyle Tucker or a top arm like Ranger Suárez or Framber Valdez? Evan argues Tucker's 162-game impact is bigger than any starter's, even while admitting the rotation still screams for certainty. The conversation rolls into David Stearns' short term, high AAV strategy, whether “connections” matter at all in free agency, and why the Dodgers are always lurking if money is close. Plus: the Pete Alonso fallout won't go away, the “is $50M worth it?” camps battle, the Yankees finally make an under the radar move with Ryan Weathers, and a caller throws Lucas Giolito into the mix as the show debates what actually qualifies as a Mets ace right now.

Rumors broke that the Mets have offered free agent OF Kyle Tucker a short-term, high-AAV deal. Chris and Jack break down what it could mean for their offseason outlook and 2026 lineup. Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

The Mets are making a real push for Kyle Tucker, with reports of a massive short term, high AAV offer that fits David Stearns and Steve Cohen's recent roster philosophy. The crew debates whether the Mets can actually beat out the Dodgers or Blue Jays, and why Tucker might prefer a short deal to reenter a thin future free agent market.

While Wild Card Weekend dominated the headlines, a major MLB bomb dropped in the background. The New York Yankees are now operating under the assumption that Cody Bellinger could sign elsewhere as contract talks stall over years, not dollars. Evan, Tiki, and Shaun break down the reported standoff with Scott Boras, why the Yankees are refusing to negotiate against themselves, and why this situation feels eerily similar to what the New York Mets dealt with last year. The conversation pivots to potential fallback options, including interest around Kyle Tucker, the realities of short term high AAV deals, and why teams like the Los Angeles Dodgers and Toronto Blue Jays loom large in the background. Plus, a deeper debate on free agency leverage, market reality, and why Yankee fans may want to stay calm as this staring contest plays out.

Welcome to the DFO Rundown with Jason Gregor and Jeff Marek! We start the show with an update from Gregor on the double Gordie and if it has been done before.New Jersey is having a very dysfunctional season, and the Dougie Hamilton saga could drag on with him having 2 years left at $9m AAV and a modified no-trade list. The Rangers got a ten-spot from the Boston Bruins over the weekend in an embarrassing 10-2 loss. Will Artemi Panarin be moved out of the Big Apple?The Buffalo Sabres are back to winning ways after their ten-game streak was snapped as they're on a three-game heater now. The Ottawa Senators have had some off-ice issues recently, but the on-ice issues might be of greater concern, as they search for answers. Can James Reimer help the goaltending in Ottawa?Vancouver has Thatcher Demko back on IR, but is this good for the Canucks in their hunt for a top draft pick? Is the hate around Gavin McKenna valid or is he still worthy of being number one overall?The Anaheim Ducks had a great start, but the young defensive core has burst at the seams. Lukas Dostal has struggled since returning from injury and the pucks are filling the Ducks' net.Zack joins the show for an edition of Buy or Sell:- The Leafs will be in a playoff spot come the Olympic break- The current Hart Trophy winner is Macklin Celebrini- The Sabres will be playoff contenders and a buyer at the deadlineA star-studded list of NHL players have had 28-plus-game point streaks, can Connor McDavid become just the fourth active player to get a 20+ game point streak?Connor McDavid is shooting a lot more and the points are piling up. Can Connor McDavid be any style of player? The superstars in the NHL don't get talked about enough, there's a lot of “and buts” around the NHL with Nathan MacKinnon is great this year but he hasn't won a Hart, Connor McDavid is great, but he's never won the Cup. The NBA doesn't have the same issue; how can the NHL change this?Marek got to meet Red Berenson and talk about Glenn Hall, Michael Hage, TJ Hughes, and Brandon Naurato. Quinn Hutson leads the AHL in goals as a rookie.The Nashville Predators are bucking some trends as they've moved up the standings to just trail the second wildcard spot. Winning while conceding the first goal, can the Preds make the playoffs? Alexander Ovechkin got goal number 20 on the season. He's second behind Gordie Howe for most 20-goal seasons trailing the legend by one season. Can Ovi chase 1000 goals? Hosted on Acast. See acast.com/privacy for more information.

Bo Bichette is reportedly unlikely to re-sign with the Toronto Blue Jays, and Kyle Tucker might have to take a short-term, high-AAV (average annual value) deal. Both of those developments could favor the Los Angeles Dodgers in their potential pursuit of one or both of the top two offensive free agents. Could this be real? Clint Pasillas and Jeff Snider are here to talk about it! Tube in all offseason long! Leave a voicemail or text the Friend of the Show hotline! (562)373-4095 Join our Discord by supporting the show on Patreon! patreon.com/realFRG Or on YouTube Members! youtube.com/@alldodgers/join All Dodgers is presented by FanDuel, part of the Bleav Network of podcasts. Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

We love to hear from our listeners. Send us a message.In episode 119 of Cell & Gene The Podcast, Host Erin Harris talks to Dr. Norman Putzki, Global Head Clinical Development, Novartis, about the FDA approval of Itvisma, now the only gene replacement therapy approved for children, adolescents, and adults with spinal muscular atrophy (SMA). Dr. Putzki walks us through the six-year development journey behind the STEER and STRENGTH Phase 3 programs. And we explore what the expanded age-range label means for patients who were previously left behind, why intrathecal, fixed-dose AAV delivery represents a pivotal advance for safety, efficacy, and scalability. He details how the Itvisma program is informing Novartis' broader gene therapy strategy across neuromuscular and CNS diseases, and more.Subscribe to the podcast!Apple | Spotify | YouTube Visit my website: Cell & Gene Connect with me on LinkedIn

Calgary Flames goaltender Devin Cooley sat down with Pat Steinberg for an exclusive chat after signing a two-year contract extension ($1.35 million AAV) on Tuesday! Cooley discusses how far he's come in his career, why the Flames have been such a great fit, his relationship with Dustin Wolf, and a whole lot more!The views and opinions expressed in this podcast are those of the hosts and guests and do not necessarily reflect the position of Rogers Media Inc. or any affiliate. https://www.sportsnet.ca/960/flames-talk/Get full Flames games and great shows like Quick 60: The Stamps Show, Wranglers Watch and more ON DEMAND.

The Tampa Bay Lightning beat the Florida Panthers 4-2 in a game that saw them take 26 penalties and go on the penalty kill 10 times. Jake Guentzel tied Brandon Hagel for the team lead with 18 goals, Pontus Holmberg scored his 5th goal and Nikita Kucherov got his 61st career game-winning goal. The Lightning's penalty kill went 9-for-10 on the night. Before the game JJ Moser signed an 8-year extension worth $6.75 million AAV. The Lightning host the Montreal Canadiens this afternoon at Benchmark International Arena.See omnystudio.com/listener for privacy information.

Julie A. Parsons, MDHaberfield Endowed Chair in Pediatric Neuromuscular DisordersProfessor of Clinical Pediatrics and NeurologyUniversity of Colorado School of Medicine, Children's Hospital ColoradoAurora, CO, USAThe gene transfer trials for musculoskeletal disorders, if we look at musculoskeletal and neurologic disorders, we really do have the highest success rate in terms of treatment, but we also carry the highest incidence of treatment-emergent severe adverse events. And why is that true? Yesterday, when we were hearing about Donovan as well, we looked and said, When the first gene transfer therapies were started, he had a single muscle that was injected.When we look at Luxturna, we injected the retina. Now, what is happening with these disorders is that we're giving these huge, massive doses of viral vector to patients. There haven't been a lot of gene transfer therapies that have reached the market. But you saw yesterday, so many gene transfer therapies being worked on, but there are very few that have actually come to market. There are a couple of reasons for that.One is with the indications that we have, we know that the musculoskeletal disorders are most likely to achieve benefit, but there are the high risk of severe adverse events. Route of Administration, IV, for most of our disorders is the way we're going. We may end up having some Intrathecal therapies as well that are coming on board, but right now it's IV, and that means, a huge dose of this viral vector and antigenic risk that is being administered.In the vector design now, we actually have more specific vectors as well as promoters that are being utilized to really target specific tissues, so that we're able to focus in a little bit more on the tissues that we want to have affected. And then the dose has gone from these little tiny local injections to really systemic, much broader. And now our patients, are larger. So we're giving a viral genome per kilo dose that is just massive as we look at that.Then there really are challenges in terms of the translation of clinical trials to commercial treatment with these agents. And we don't always know, we're not always great when we do tests in clinical trials in small populations, about when that's broadened to the commercial availability and we hit larger heterogeneous populations.There are safety issues arising from these therapies, and I think that we have some experience now, certainly with the three diseases that I mentioned at the beginning, in terms of collecting some data and information to have a little bit more of an idea what to expect. Although to me, the recurring esteem is always, expect the unexpected. Because we still are learning about this. Hepatotoxicity. We know that transaminitis is something that we see in almost every gene transfer therapy that has been delivered, and we have to watch really, really closely and follow our patients closely for this. We also have to select patients that we don't think have risk for additional liver injury or underlying liver pathology, because as we found out in the XLMTM boys, we missed that. Thrombotic Microangiopathy. We look at this disorder. We've had deaths in SMA from TMA. We have Duchenne patients that have had TMA.This is scary because as many of us as clinicians who have treated patients, you know that we end up getting thrombocytopenia. So is that it this time, or are they going to be fine, or the platelet is going to go back to normal? This is another one that we have to watch really, really closely for. Cardiac Toxicity. We have had cardio myositis. We've had deaths from cardiac toxicity.Something really, really important for us to think about. In little kids, vomiting could be a sign of cardiac myositis. And for most of us who've treated patients with gene transfer therapy, what's one of the first issues that you get?You get nausea of vomiting, they don't feel good. So is that myocarditis or is it just a standard side effect that we're seeing with treatment? Importantly, as we discovered, there actually can be an immune response to the transgene. It's not just the viral vector capsid, it's actually the transgene as well. That was discovered in patients who were treated for Duchenne. So that's a really important thing in terms of looking now at what's our patient's selection and how do we pick the right patients.Next part, Dr. Parsons will discuss understanding and preparing risk factors associated with AAV gene therapies.

Drs. Beggs and Parsons discuss the current status of gene therapies in rare neuromuscular disorders in this eight-part podcast series. This is derived from the symposium that was presented at the MDA 2025 conference in Dallas, Texas, in March 2025, and is intended for healthcare professionals only.This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established in contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses. The ASPIRO clinical trial is on clinical hold since September 2021. In this part, Dr. Beggs will provide an introduction to gene-directed therapies.Alan Beggs, PhDI'm going to talk now about challenges, a little bit of background in the history and the development of AAV-mediated gene therapies, in particular for neuromuscular disorders. There are a lot of aspects about neuromuscular disease that make it a good group of conditions to target by gene replacement therapies. These are traditionally single gene disorders with known identified oftentimes protein deficiencies, so null mutations leading to lack of a protein.The primary tissue, the therapeutic target is a skeletal muscle, and so we can target that with the appropriate viral vectors. There's a major unmet medical need and substantial clinical burden for these conditions. As rare diseases, they place a very substantial burden on both health systems and patients, both economically and in terms of personal difficulties.I like to think about gene therapy, which is generically used for one category of this, to really think about gene-directed therapy. So this would be any therapy directed at the nucleic acids that are either encoding our DNA or are encoding the messenger RNA transcripts. So one approach to a gene-directed therapy can be directed at the RNA level. I think you're all familiar with the Exon-skipping approaches that target mRNA splicing.There are other methods for either knocking down toxic gain of function messenger RNAs, and there are methods now being developed to edit messenger RNAs. So this represents one class of gene therapy. You can also approach gene therapy at level of DNA by editing or changing the DNA in situ. So various CRISPR-Cas9-based approaches. There's now prime editing and other approaches for genetic engineering that target specific locations, often using bacteria endonucleasis that target with oligenucleotides that target specific sites.And then finally, there's gene replacement therapy, which is what we're going to spend most of our time on today, which really aims to not take away what's there and replace it, but to replace the missing protein product by providing a copy of the healthy or the complete wild type gene. Often, it can either be integrated into the chromosomes or remain extrachromosomal.So whether or not that happens really depends on the type of vector or approach you use. You can see here a number of different approaches for transferring in a therapeutic gene. The two most commonly used in clinical trials are lentivirus and AAV, and they have different strengths and weaknesses. Lentiviruses are used frequently for hematologic diseases.Lentivirus is a member of the retrovirus family and has the characteristic that it actually integrates into the DNA. So lentiviral treatments tend to be long-acting. However, they also suffer from the risk that by integrating into the DNA, you might have site-directed mutagenesis. And there have been known instances of cancers that arose through integration at the wrong site.In the next part, Dr. Beggs will cover the history and challenges in the development of AAV-mediated gene therapies.

Alan Beggs, PhDDirector of the Manton Center for Orphan Disease ResearchSir Edwin and Lady Manton Professor of Pediatrics, Boston Children's HospitalHarvard Medical School, Boston, MA, USA Julie A. Parsons, MDHaberfield Endowed Chair in Pediatric Neuromuscular DisordersProfessor of Clinical Pediatrics and NeurologyUniversity of Colorado School of Medicine, Children's Hospital ColoradoAurora, CO, USADoctors Beggs and Parsons discuss the current status of gene therapies in rare neuromuscular disorders in this eight part podcast series. This is derived from the symposium that was presented at the MDA 2025 conference in Dallas, Texas, in March 2025 and is intended for healthcare professionals only. This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established. In contents of this podcast, shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses. The ASPIRO clinical trial is on clinical hold since September 2021.In this part, Doctor Beggs will provide an explanation of AAV-mediated gene therapies.Alan Beggs, PhDAAV vectors, which I'm going to be talking about more today, or Adeno associated viral vectors are small viruses. Their DNA gets delivered into the cell and remains extrachromosomal. There are very rare occasional integrations, but the risk of oncogenesis as a result is significantly lower as a consequence of remaining extrachromosomal, though, we do have to think about what happens as the cells divide and potentially the durability of treatment is more limited.There have been a lot of movement and development over the years, starting back in the 1980s when the first AAV genomes were isolated and sequenced. This led to a development of methods to produce recombinant AAVs that would lack the genes necessary for viral replication, but contain a therapeutic gene you wish to deliver. Through this, the structure of AAVs have been developed. There have been isolation of a number of naturally occurring variants. You've heard of AAV8, AAV9, also RH 74, derived from a rhesus monkey for the RH. These have all been used in clinical trials. Then at the end I'll talk a little bit about directed evolution methods to actually engineer capsids with particular properties that are beneficial.Throughout this we've identified some of the issues that arise in this. It was initially thought that AAV vectors were non-immunogenic, but in fact there are immune responses not just to the viral payload to the therapeutic protein, but also to the viral vectors, and you're going to hear about that from Doctor Parsons. Over time, as we've come to understand these challenges, we've also been developing approaches to mitigate them. In terms of clinical trials and treatments, the very first studies were done back in the 1970s.By the early 2000, the very first clinical therapeutic was approved in China. It was actually an oncolytic virus carrying a p53 gene to treat head and neck cancers. By now there are over 40 approved treatments for various types of AAV delivered gene therapies. Of course, the ones we know a lot about are Zolgensma, which was approved in 2019, and Elevidys, which was approved last year. A number of challenges and then also a number of approaches to overcome those challenges. First of all, the preclinical data are not always sufficient to predict the response of a human patient.For example, in X-linked myotubular myopathy we had mouse and dog models that exhibited a myopathy but nothing else, and yet when we treated human patients, we discovered that patients with X-linked myotubular myopathy actually had a previously only poorly recognized hepatopathology that led to potential liver consequences following gene therapy. The animal models don't always predict the clinical outcome in humans.Also, we have small disease populations. These are rare diseases. It's important to understand the natural history of these diseases, understand the heterogeneity among the clinical population. It's very important to engage with families and with patients and communities, understand who might be at increased risk to treatment with one of these. This feeds into safety considerations. We need to think also about some of the immune responses. I think we're starting to learn, for example, with the gene therapies for Duchenne, and we know this from SMA that some patients get into trouble and others don't. We need to understand why that may be, and we don't know about the long term effects. This has been very recent.

Alan Beggs, PhDDirector of the Manton Center for Orphan Disease ResearchSir Edwin and Lady Manton Professor of Pediatrics, Boston Children's HospitalHarvard Medical School, Boston, MA, USAThe challenges that you've heard about are real. Some of them I think we could have foreseen others. There was no way to know until we actually started treating patients in clinic. But we now know that there are immune responses and also responses just to the viral load. As Julie mentioned, we're giving massive doses to these patients on the order of one times ten to the 14 viral genomes per kilogram.Think about the fact that when these capsids are manufactured, there's a certain percentage of empty capsid. The amount of protein that's being delivered to these patients can be massive. One of the approaches to mitigate some of the risk would be to lower the dose. While early studies demonstrated that in order to get adequate delivery to skeletal muscle, you need to give these very large doses. But what if we could engineer a viral capsid that would be potent at lower doses?There has been quite a bit of research in this area that's ongoing, and some new next generation vectors that are just starting to enter the clinic. In particular, there are a class of Myotropic viral vectors or capsids so-called RGD vectors. RGD refers to arginine, glycine, and aspartic acid, which are three residues which, when present at a particular point in the viral capsid proteins interact with integrin receptors that are specific for skeletal muscle. These viral capsids home to skeletal muscle and can deliver their genetic payload at much lower doses. There was one group of these developed in Germany by Theo Grimm's lab.These were the so-called AAV Myos, and simultaneously in Boston at the Broad Institute, a group of capsids was developed that were called Myo AAV. These were both based off of an AAV nine backbone. It's basically an AAV nine legacy vector with these three amino acids changed. Now Solid Biosciences also has their own independently derived vector that I believe is also an RGD vector. These vectors give us the potential then for more efficient and specific delivery to muscle cells.They may or may not target the liver depending on the particular virus. Some of them the risk to the liver is mitigated by delivering a lower dose. You can also develop these vectors in a way that will be liver targeted, that specifically less of it gets delivered to the vectors. These would be really, in my mind potentially third generation vectors.Strategies, there are a number of strategies. You heard about the immunomodulation regimens. I just talked about optimizing vector design. Also, Doctor Parsons mentioned earlier the fact that where you deliver so zolgensma is delivered Intrathecally. We get it to the place we need it, and we're less likely to have off target effects through other tissues.Then improved manufacturing is very important. I mentioned the fact that every viral preparation contains empty capsids. There are ways to minimize the production of empty capsids, and also effective ways to filter out and remove those empty capsids. This is actually a very important aspect that is being developed further by the CMO community. Then in summary, I think it's important to take a holistic approach when we're thinking about the development of AAV based gene therapies for neuromuscular disease.It starts from the fact that for any given disease we're interested in, we need to define the genetic etiology. Since these are gene directed therapies. We need to pay careful attention to the preclinical animal models. How accurately do they really reflect the human condition? Or are there potentially responses in our human patients that we haven't experienced in the animals? It's important to understand the natural history and the patient population.Recognize that there's extensive heterogeneity, not just in age and severity, but also potentially in underlying susceptibilities in our patients. We have a group of toxicities that we know about and can anticipate. But as Julie was saying, you need to be really careful and think about any potential unexpected SAEs. And then finally I mentioned the manufacturing aspect, the development of newer vectors and quality control aspects that go into making a safe and effective therapeutic.In the next part. Doctor Parsons will discuss clinical safety and efficacy observed in AAV mediated gene therapy programs in DMD, SMA, and XLMTM.

Julie A. Parsons, MD Haberfield Endowed Chair in Pediatric Neuromuscular DisordersProfessor of Clinical Pediatrics and NeurologyUniversity of Colorado School of Medicine, Children's Hospital ColoradoAurora, CO, USAAs we talk about the gene transfer therapies and the modalities that we have to use, it's really interesting. Yesterday, with our keynote speaker, you could see this logarithmic growth of the use of gene transfer therapies for these disorders. If you look at the Venn diagram, you can see that really 27% almost of gene transfer therapies that are used are in musculoskeletal and neurology. For many of us as neurologists, we also take care of metabolic disorders.We really own right now this landscape, and of course, our two approved modalities are Onasemnogene and Delandistrogene. We're going to look at three different disorders, monogenic disorders, monogenic diseases, to typify what we look at in terms of some of the risks and benefits of these treatments. SMA, Duchenne, and X-linked myotubular myopathy are all rare disorders. They're all diseases that have a high unmet medical need and a significant disease burden.I think they're all good in terms of typifying where we are clinically with these disorders. The first question is, is it worth it? Are these effective treatments? We know from looking at the information about SMA that just looking early on, we know that if we treat kids early, that we do see a marked improvement in motor scores for kids that are treated early with Onasemnogene.In Duchenne, we have information that there is at least some improvement in the 4-5-year-olds in terms of motor skills treated with Delandistrogene. In terms of X-linked MTM, which was a very dramatic improvement, you could see that for boys who were basically traked, vented, and had no mobility, the bottom line, the blue line, is actually looking at ventilator dependence. Are they effective? Yeah, they're effective, but then we have to say, okay, what's the downside?The downside is that there's tremendous risk associated with treatment with these agents. If we really look at the sobering facts, we know that with SMA, there have been deaths, there have been fatalities related to thrombotic microangiopathy to patients who have liver failure, a couple of patients have died. With Onasemnogene, this is 4,000 plus doses that have so far been given. With Duchenne, unfortunately, many of us got the letter yesterday talking about an additional death in a patient treated with commercial Delandistrogene.We also know with some of the other agents, like fordadistrogene, patient died of heart failure, cardiac arrest, another patient who had acute respiratory syndrome with pulmonary edema. Again, we look at this and say this is significant. With X-linked MTM, as Alan said, there were some unanticipated deaths, four deaths from patients who ended up having cholestatic liver diseases that really wasn't anticipated prior to the patients being treated with the animal models and all that we had. Then many of you have heard about the patient with Rett syndrome who had a systemic hyperinflammatory syndrome. Again, these are rare disorders. They have a high disease burden, but the risk of treatment is significant.In the next part, Dr. Parsons discuss factors impacting safety and efficacy of AAV-mediated gene therapies.

Julie A. Parsons, MD Haberfield Endowed Chair in Pediatric Neuromuscular DisordersProfessor of Clinical Pediatrics and NeurologyUniversity of Colorado School of Medicine, Children's Hospital ColoradoAurora, CO, USAHow have programs adapted to the experiences from clinical trials? I'm just looking at SMA because we've had SMA. We've had onasemnogene around for the longest period of time. We want to always confirm a diagnosis and know that the patient is right. We do antibody testing for these disorders prior to delivering the AAV therapies. We have to know that the product that is incredibly expensive is handled appropriately by the institution. Dealing with the pharmacy, making certain that you handle the agent properly, patients need to be pretreated at this point with prednisone, and that really has to happen so that you know that they're ready for treatment, that they don't have any infections prior to treatment.Then we need to monitor and provide medication and follow-up afterwards. As I said, I think this is really, really important to make sure that you're connected well with the patient. If you live in an area as we do, that has a huge catchment area with patients that come from hundreds of miles away, sometimes they need to stay with us for a period of time, so that we can ensure the safety and follow-up of these patients after we deliver gene therapies.Again, a recurring theme is the patients that you're treating who are not in a clinical trial are not the homogeneous, well-selected patients. It's really all actors. The population that you're treating commercially is very different. We're now moving into treating patients with larger body masses and older ages. We don't always know, because those patients haven't really been included in the clinical trials. We don't really know what some of the effects are going to be with that group of patients as well.I am a neurologist. I am not an immunologist. I have had to learn a lot of immunology at this point, but it's still not sufficient. I think that we also need to reach out to our subspecialist colleagues who really do have more experience than we do to try to help us with some of these issues, because as we look at these viral vector capsids and the transgenes, we have to say, is there something that we can do to mitigate the immune response that we're seeing when we're giving massive doses of these agents and really taxing the immune system in our patients?Looking at possibilities, we give steroids, and that's really what we've done. That was what was done in the early clinical trials with MENDEL. It's like, okay, prednisone, that's all we have to do is we give steroids and everybody will be fine. That really isn't maybe the answer. As we have more information, we know that we're going to start with steroids, but we're really going to look at, is there a way to block both the B-cell response, the T-cell response? Is there something that we can do so that we don't have to sit on the edge of our seats and not sleep for months after we treat these patients?At least in a trial, was done looking at patients who were treated just with corticosteroids. Those patients had rapid increases in IgM and IgG. There's complement activation. Both the adaptive and the acute immune responses are triggered. That's really what we're doing as standard practice right now, but in the trial looking at treating patients and pretreating patients with rituximab blocking B cells and sirolimus and corticosteroids, then no significant change in IgM, IgG.Is that something that we should be doing? I think that some of the clinical trials that are being set up are looking at instituting some of these immune-modulating features to see whether or not their outcomes are improved. Can we do anything proactively to prevent our patients from having some of these very severe events or fatalities? I think that's really what we need to be looking at now. I think we are looking at that as a community, and to me, is a story that is still unfolding in terms of how we keep our patients safe.In the next part, Doctors Beggs and Parsons will discuss key issues on gene therapy development.

Alan Beggs, PhDDirector of the Manton Center for Orphan Disease ResearchSir Edwin and Lady Manton Professor of Pediatrics, Boston Children's HospitalHarvard Medical School, Boston, MA, USA Julie A. Parsons, MDHaberfield Endowed Chair in Pediatric Neuromuscular DisordersProfessor of Clinical Pediatrics and NeurologyUniversity of Colorado School of Medicine, Children's Hospital ColoradoAurora, CO, USAThe ASPIRO Clinical Trial is on clinical hold since September 2021. In this part, Doctors Beggs and Parsons will discuss key issues on gene therapy development.Question: Is there a standardized immunomodulation regimen being considered for gene therapy?Julie A. Parsons, MDAs I mentioned, right now, I think there are a number of different concepts that are being utilized. We don't really have a recommended standard regimen at this point. There are a number of different trials that are ongoing looking at trying to answer this question. In some of the clinical trials, there is an immune modulating regimen that is being put in place but being looked at. There isn't anything that we have as a standard at this moment for all gene transfer therapies, but I'm hopeful that we will come up with something that really makes sense in each patient population as we go forward with specific gene transfer therapies.Question: What are the long-term implications, safety and efficacy of a one-time gene therapy in pediatric patients with neuromuscular diseases?Alan Beggs, PhDOne question is the efficacy. For example, Donovan Decker's story, he had an experimental treatment of one muscle. It was a phase one safety trial, and he knew that nothing was going to come of it in terms of direct benefit to him. As a result, though, 25, 30 years later, he still has a tighter against AAV vectors. He's not a candidate for gene therapy under current protocols, although there's a lot of work going on to redosing. But for now, it's a one-time treatment. What you get is what you get, and there's not a chance to go back and do it again.The other question is durability. We really don't know about the long-term durability for these treatments. I should say that, for example, in the studies that we did, David Mack, who's here in the audience, managed a dog colony for a dog model of excellent tubular myopathy. Those animals lived 10 years in a... We never used the C-word, but they were cured. They were healthy, happy, normal dogs who would have had to be put down at 6 months of age otherwise. And then, as we heard, I'll let you talk about the concern for unanticipated SAEs as time goes on, but I think there's other aspects we need to think about.Julie A. Parsons, MDYeah. I think that this is really the key question that all of us are going to need to help answer over the next several years. Efficacy, we're looking at outcomes, and outcomes come in a variety of flavors. I think we do a decent job with motor outcomes. We don't do a decent job with some other outcomes. I think we need to look more broadly in terms of what we mean in terms of beneficial outcomes and really take some of those cues from the patients themselves about if these are efficacious treatments, because, again, the risk is high as we deliver these agents, and we need to know that it's worth it to the patients and families.In terms of safety, we're working on it. There are all sorts of things that are coming forward as issues with these patients. I think that collectively as a community, that our responsibility is to follow patients for the long term. There are lots of registries and outcome studies. We're not very good as a community about reporting adverse events to central groups. We're not great about broadcasting that to each other in real-time. I think those are things that we really need to work on as a community in terms of helping with the safety issues so that we all have a communal better understanding of what some of those issues are.

In this episode of BioTalk Unzipped, hosts Gregory Austin and Dr. Chad Briscoe sit down with Glafabra CEO: Dr. Chris Hopkins, geneticist, biochemist, and biotech entrepreneur, to explore the science and strategy behind next generation cell-based gene therapies for rare diseases.With more than 25 years of experience spanning gene augmentation, rare disease biology, CRISPR licensing, and biotech formation, Dr. Hopkins shares how autologous, ex vivo engineered cell therapies may overcome key limitations of current enzyme replacement and viral gene therapies, particularly for Fabry disease.The conversation dives deep into: • How lentiviral gene augmentation in patient derived cells enables sustained enzyme production • Why redosing matters and where one time AAV therapies fall short • The scientific rationale for early intervention, including potential newborn treatment • Differences between autologous and emerging allogeneic approaches • Regulatory pathways for rare disease therapies and recent FDA developments • The role of non animal models in translational research • Montana's early access therapy law and its broader implications • Building biotech platforms amid a challenging funding environmentTopics include cell based gene therapy, Fabry disease, lentiviral vectors, stem cell engineering, rare disease drug development, regulatory science, and translational medicine. Subscribe to BioTalk Unzipped for in depth conversations with the scientists and leaders shaping the future of biomedical innovation.00:00 - Intro00:53 – Welcome to BioTalk Unzipped, Guest intro: Dr. Chris Hopkins02:10 – Guest charity: Environmental Defense Fund03:12 – His journey into rare-disease therapeutics and Glafabra05:58 – Discovering a new enzyme-deficiency therapy 06:39 – Current standard of care 07:42 – How the new autologous cell therapy works09:40 – Treating patients earlier (even newborns)10:33 – Emerging therapies - AAV gene therapy vs. cell-based therapy12:16 – Long-term results & repeat dosing14:30 – Future plans: T-cells & allogeneic approaches18:08 – New News: FDA resubmission for rare disease20:00 – Navigating FDA pathways22:06 – Non-animal testing & alternative models25:50 – Montana's early-access therapy law & medical tourism29:03 – Could other states follow?31:31 – Biotech's current funding challenges33:46 – New News: Gene therapy trial saves 4-year-old37:09 – Long-term vision for expanding therapies39:53 – Personal segment: outdoor life & skiing44:43 – Guest question on international trade Dr. Christopher Hopkinshttps://www.linkedin.com/in/christopherehopkins/ Glafabra - https://www.glafabra.com/ Environmental Defense Fund - https://www.edf.org/ Dr. Chad Briscoe

Nicola Longo MD, PhD, and Mark Roberts, MD Nicola Longo MD, PhDProfessor and Vice Chair of Human Genetics,Allen and Charlotte Ginsburg Chair in Precision Genomic Medicine,Division of Clinical Genetics, Department of Human Genetics,University of California at Los Angeles (UCLA), Los Angeles, CA, USAMark Roberts, MDProfesor and Consultant Neurologist,University of Manchester, Manchester, UKResearch Lead for Adult Metabolic Medicine at Salford Care Organisation, Manchester, UKDrs. Longo and Roberts discuss the current status of gene therapies in rare neuromuscular disorders in this eight-part podcast series. This is derived from the symposium that was presented at World Symposium 2025 in San Diego, California on February 4th through 7th, 2025 and is intended for healthcare professionals only. This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses. The views, thoughts, and opinions expressed in this presentation belong solely to the author and are subject to change without notice.The contents of this presentation do not constitute an endorsement of any product or indication by Astellas. In this part, Dr. Roberts will discuss vectors, different strategies, modes of administration and targets in gene replacement therapies.Mark Roberts, MDNow in the broader sense, gene replacement therapy seeks to actually deliver genetic material directly into the host cell to influence gene expression. In the most simple idea, one of course has a vector, this is most commonly but not exclusively a virus, which can then be given intravenously for example, and can hope to potentially correct the condition within the individual cells using novel transgenes. Suitable candidate conditions for this as examples of genetic conditions are now well understood. And crucially, this applies not only towards some more recessive, but dominant and even accident conditions.Across the piece, one can see for example, mitochondrial problems, spinal muscular atrophy as is well known, X-linked myotubular myopathy, Duchenne muscular dystrophy, a very common condition affecting one in 3000 male individuals, Pompe disease of course, an important focus of the meeting here, but other very common conditions, for example, cystic fibrosis, immunological conditions and perhaps obviously very crucial in early work on gene therapy, hemophilia.Let's now think about the approaches to gene therapy. One can seek to work at the DNA level and gene replacement. In essence, one is trying to put a new transgene through into the nucleus that will ultimately be transcribed and translated and produce the important functional protein that is lost. Gene editing which is a very exciting new technology or CRISPR technology actually seeks to actually modify in vivo the actual mutations that are responsible for the pathogenic production of abnormal proteins and correcting these and actually producing a more normalized protein.But of course there are also RNA approaches where one seeks to actually repair the mRNA transcripts copied from the mutated gene. For example, this may be a novel approach that could be extremely useful in myotonic dystrophy, a multisystem condition. When we talk about the viral vectors, predominantly we're talking about viruses. Those such as adenoviruses and AAV viruses which have the virtue of not integrating into the host genome or at least not in a large amount, and those which deliberately seek to integrate into host genome such as retroviral or lentiviral systems that may be particularly useful for ex vivo systems.There are of course other ways to get genetic payloads into the nucleus, various polymers, nanoparticles and even cell penetrating peptides. Nanoparticles in particular is certainly on the ascendant. That being said, in a recent review of the clinical trials in gene therapy, it was certainly the viral vectors that stood out both in direct gene replacement with lentivirus and AAV, but also actually as delivery systems, for example, for gene editing. An example of what one is seeking to do with AAV, so of course one seeking to remove the native DNA, insert the new transgene directly into the vector and of course keen to make sure that there's a high transmission into the capsid producing a recombinant AAV, which then can be given as a treatment and hopefully produce a therapeutic increase in the functional protein that is deficit in the disorder.In the next part, Dr. Roberts will discuss immune responses and other safety concerns related to gene therapies.

Nicola Longo MD, PhDProfessor and Vice Chair of Human Genetics,Allen and Charlotte Ginsburg Chair in Precision Genomic Medicine,Division of Clinical Genetics, Department of Human Genetics,University of California at Los Angeles (UCLA), Los Angeles, CA, USAMark Roberts, MDProfessor and Consultant Neurologist,University of Manchester, Manchester, UKResearch Lead for Adult Metabolic Medicine at Salford Care Organisation, Manchester, UKDrs. Longo and Roberts discussed the current status of gene therapies in rare neuromuscular disorders in this eight-part podcast series. This is derived from the symposium that was presented at World Symposium 2025 in San Diego, California on February 4th through 7th, 2025, and is intended for healthcare professionals only. This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses. The views, thoughts, and opinions expressed in this presentation belong solely to the author and are subject to change without notice. The contents of this presentation do not constitute an endorsement of any product or indication by Astellas. In this part, Dr. Longo will discuss ongoing gene therapies in lysosomal disorders.Nicola Longo MD, PhDI'm going to present to discuss some example of ongoing gene therapy for lysosomal disorder. There are gene therapy in development for both Fabry disease and some of this involve ex vivo gene therapy, many others involve systemic administration with an AAV, Gaucher disease type 1 that affect the periphery, and Gaucher disease type 2, where the replacement should occur within the central nervous system because this condition affects the brain. There is already one approved gene therapy for lysosomal disorder, which is for the early onset metachromatic leukodystrophy. This has been approved both in Europe and now even in the United States, which consists of ex vivo gene therapy with the administration of an extra gene that restore the function of the defective enzyme. Now there are many others that are ongoing for the same indication. There are gene therapy programs for GM1 and GM2 gangliosidosis, and at least one for Krabbe disease. It is important to know that some of these condition are actually included in the recommended uniform screening panel. Basically, we would have access to patients in a timely manner for some of these conditions. Then there are several gene therapy under development for the mucopolysaccharidoses, including MPS-IH, MPS-II, MPS-IIIA and MPS-IV.There are different type of lysosomal disorders, the one caused by mutation, integral membrane protein, not enzyme within the lysosome, but protein that are present on the membrane of the lysosome. This gene therapy that have been tested, it is for cystinosis, that it is caused by a defective lysosomal and for Danon disease, which is caused by a deficiency of an integral membrane part. Finally, one lysosomal disorder, which obviously seems a metabolic condition, but it is really not, is glycogen storage disease type 2 or Pompe disease, in which there is the intralysosomal accumulation of glycogen. There are several ongoing clinical trials to try to correct the problem in this condition.Now, I'm going to discuss some of the most advanced program in the lysosomal storage disorder. This include one for Fabry, which is on an accelerated approval pathway with phase 1 and 2 data, one for Gaucher disease type 1. Obviously, I'm going to discuss the one that has been already approved for metachromatic leukodystrophy. There is one for Hunter syndrome, and the difference of the one for Hunter syndrome, it is an example of the direct administration of gene therapy within the central nervous system.Finally, there is one ongoing for glycogen storage disease type 2 or Pompe disease in adult patients. In gene therapy for metachromatic leukodystrophy, it was the first gene therapy approved for lysosomal disorder in human, and this requires harvesting the CD34 cell from affected patient and then introducing the [inaudible 00:04:32] gene back in this cell, and then placing them back inside the patient again. This has been very effective in patients who were treated early, and obviously, the treatment needs to occur before there is irreversible brain damage in this patient.In the next part, Dr. Roberts and Longo will discuss treatment with gene therapies.

Nicola Longo MD, PhD, and Mark Roberts, MDDrs. Longo and Roberts discussed the current status of gene therapies in rare neuromuscular disorders in this eight-part podcast series. This is derived from the symposium that was presented at World Symposium 2025 in San Diego, California on February 4th through 7th, 2025, and is intended for healthcare professionals only.This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses. The views, thoughts, and opinions expressed in this presentation belong solely to the author and are subject to change without notice. The contents of this presentation do not constitute an endorsement of any product or indication by Astellas.In this part, Doctors Roberts and Longo will discuss treatment with gene therapies.Question: Can one administer AAV-mediated gene therapy repeatedly?Mark Roberts, MDI think the traditional view would have been no. One can think of gene therapy as a silver bullet. Hopefully, it will reach its target. But if it's not effective, that bullet has been shot, the immunological response has occurred, and it means redosing, at least with that particular vector, may become difficult. But this situation is changing and evolving as we have better understanding of immunological modulation for repeat testing. We were discussing this yesterday evening, weren't we, Professor Longo?Nicola Longo MD, PhDCorrect. Basically, the current AAV-based gene therapy cannot be readministered. It is either effective, or it doesn't work. The other thing is that even though in theory, one could utilize a different AAV vector with different immunogenicity, there is many times cross-reactivity among the different adenovirus, adeno-associated viruses. Now, there are approaches in animal models in which you give a strong immune suppression to prevent the creation of the immune response against the adeno-associated virus, and at least in the animal model, it has been possible to give some of the gene therapy repeatedly.The second approach that is being tested is with gene correction therapy, in which by using an RNA guide and the CRISPR/Cas9 system delivered by lipid nanoparticles, you basically correct some of the effective genetic information. Obviously, since this is done by lipid nanoparticles and not by an AAV, the immunity that you create is really not there. You can give this one repeatedly, and in theory, it can be given more than one time. But again, you are absolutely correct. The current gene therapy cannot be given twice, and either it works or it doesn't work.Question:vWill gene-therapy-treated patients be able to go back to the standard of care or enzyme replacement therapy?Mark Roberts, MDI think when we're talking to patients about the potential benefits of gene therapy and the amelioration of the requirement to have these infusions on a regular basis of ERT, the hope is that will work, but they need to be reassured that we can potentially go back to the ERT. Gene therapy is an important treatment, but we don't know the destination of the patient at the beginning, and we have to make it available to them to go back to ERT.One of the crucial questions, of course, though, is the basis of the immunological reaction that perhaps prevented the gene therapy being effective. If it's against the viral vector, well, okay. If it's against the transgene, not great. If it's against the functional protein, that becomes more difficult. It is somewhat, I think at this time, to be fair to say to patients, think of gene therapy as a trial treatment. It is somewhat a leap of faith and an important observation, of course, for the patient community, but just be aware there may be downsides.Nicola Longo MD, PhDThey totally agree with Dr. Roberts. In general, they should be able to go back to enzyme replacement therapy if the gene therapy is not effective. However, what we are starting to appreciate is that we need to understand the immune response, not just to the enzyme replacement therapy, but also to gene therapy. What this field is doing is forcing geneticists to deal with the immune response. I feel that historically has not been dealt together. The two things need to be integrated. The advantage of the gene therapy is that the protein is produced endogenously. There should be the development of some degree of tolerance with time in the body towards the endogenous continuous production of a protein.Now, will that happen all the time? I still do not know. Again, we need to understand much better what is the integration of the immune system with the response to gene therapy in the ongoing clinical trials.

Cody and Vince are live with a brand new episode of Talkin' Blue, breaking down the latest Dodgers and MLB news. Mookie Betts has officially decided not to participate in the upcoming World Baseball Classic, with his wife expecting their third child around that time. We discuss Mookie's decision, what it means for Team USA, and why family always comes first. The Kyle Tucker market remains open, and we explore whether a short-term deal with a higher AAV could make sense. Is Tucker waiting things out, and could the Dodgers still be lurking? Tyler Glasnow also addressed recent trade rumors and shared his excitement about the idea of playing alongside Tarik Skubal if the Dodgers were to land him. We break down what that would mean for the rotation and whether the buzz has real legs. Plus, more WBC news, roster chatter, and live fan reactions throughout the show. Tap in, join the conversation, and Talk Blue with us. Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com for information about our collection and use of personal data for advertising.

Dodgers sign Edwin Diaz for 3 years! setting a AAV record for relievers. Giants get off their ass, kinda. They sign Jason Foley who wont be back til mid season and Adrian Houser to a 2 year deal with a 3rd year club option

2025 MLB Winter Meetings Recap: Schwarber Re-Signs with Phillies, Díaz to Dodgers, Alonso Joins Orioles & Post-Meetings Moves! Join us as we break down the action-packed 2025 MLB Winter Meetings in Orlando (Dec 8-11), featuring blockbuster free agent signings like Kyle Schwarber's 5-year, $150M return to the Philadelphia Phillies, Edwin Díaz's record AAV deal with the Los Angeles Dodgers, and Pete Alonso's 5-year, $155M pact with the Baltimore Orioles! We also cover post-meetings developments, including Kenley Jansen to the Tigers, Merrill Kelly back to the Diamondbacks, and ongoing rumors around Kyle Tucker, Tarik Skubal trades, and more offseason buzz as of December 15, 2025. From reliever reinforcements to slugger splashes, analyze how these moves reshape 2026 contenders! Perfect for MLB fans, fantasy baseball players, and hot stove enthusiasts. #MLBWinterMeetings2025 #MLBOffseason #KyleSchwarber #EdwinDiaz #PeteAlonso #MLBFreeAgency Subscribe for daily MLB hot stove updates, hit the bell , and share your thoughts in the comments! Who's the biggest winner of the offseason so far?

BT & Sal kick off the show with WWE Executive Director Bruce Prichard (aka Brother Love) to discuss John Cena's final match, the evolution of wrestling, and who is the "toughest legitimate alpha" in the locker room today. Then, the focus turns to the New York Mets after Edwin Diaz signed with the Dodgers. Sal explodes after learning the Mets offered three years, $66 million and the deal-breaker was Diaz's desire to be the highest AAV closer—revealing Diaz chose the Dodgers, not the money, but for the status. Sal's fiery retort labels Diaz a "traitor," slamming the trumpets, his 2019 disaster, and his 2024 sticky stuff suspension. The guys ultimately side with the "unkillable" duo of Steve Cohen & David Stearns, believing the organization will bounce back and address the team's many holes.

BT & Sal explode over Edwin Diaz's shocking defection to the Dodgers for a record AAV, concluding that the closer "didn't want to be a Met" and chose status over the Mets' near-matching $66M offer. Sal rips Diaz as a "traitor" while the hosts ultimately side with the "unkillable" duo of Steve Cohen & David Stearns as they brace for a rebuild. The chaos fuels a fierce debate over Pete Alonso's future, with Sal criticizing Pete for "shopping himself" at the Winter Meetings while his potential Hall of Fame pace is fiercely debated. They dissect Kyle Schwarber's new contract and its massive implications for Alonso's market price. The show is rounded out by a hilarious dive into obscure baseball slang and a serious sit-down with WWE Executive Bruce Prichard (Brother Love) about John Cena's final match and wrestling's toughest "alpha."

Tomlin Takes – What else did Mike Tomlin say to the media today? PG writer Noah Hiles joined the show. Noah said the offer to Kyle Schwarber from the Pirates was legitimate and actually higher than what he signed for, in AAV, with the Phillies. Noah said it's not worth celebrating because they didn't land the player, but this should mean the Pirates are willing to spend that money elsewhere. Noah didn't think it was a coincidence that the Pirates' offers were the ones that were openly put out there. Noah thinks it could tell other players that the Pirates are willing to spend, but it was probably leverage being played on both sides. How will the Pirates handle some of the other notable names on the market? Noah said Jorge Polanco is the top, realistic player on his list, but that shouldn't stop the Buccos from going after Ketel Marte. He said there are ways to get around a player's no-trade clause list, but it means they have to sweeten the deal. Noah believes the Pirates cannot show up ‘empty-handed' to Pirate Fest this year after the words that have been thrown around this off-season. Noah pointed to a particular agency that could be a way for us to follow the tea leaves. Name Game.

PG writer Noah Hiles joined the show. Noah said the offer to Kyle Schwarber from the Pirates was legitimate and actually higher than what he signed for, in AAV, with the Phillies. Noah said it's not worth celebrating because they didn't land the player, but this should mean the Pirates are willing to spend that money elsewhere. Noah didn't think it was a coincidence that the Pirates' offers were the ones that were openly put out there. Noah thinks it could tell other players that the Pirates are willing to spend, but it was probably leverage being played on both sides. How will the Pirates handle some of the other notable names on the market? Noah said Jorge Polanco is the top, realistic player on his list, but that shouldn't stop the Buccos from going after Ketel Marte. He said there are ways to get around a player's no-trade clause list, but it means they have to sweeten the deal. Noah believes the Pirates cannot show up ‘empty-handed' to Pirate Fest this year after the words that have been thrown around this off-season. Noah pointed to a particular agency that could be a way for us to follow the tea leaves.

Welcome to Daily Faceoff Live with Tyler Yaremchuk and Carter Hutton!We start the show with concern growing in Utah, as the Mammoth have won just two of their last ten and are riding a four-game skid after a 6–3 loss to the San Jose Sharks. The franchise hasn't reached the postseason since 2020—back when they were still the Arizona Coyotes in the COVID-shortened season. Will the Mammoth find a way back into the playoff picture?The Florida Panthers remain without several key players, and the healthy bodies they do have aren't pulling their weight. The two-time defending Stanley Cup champions sit seventh in the Atlantic Division, six points out of a wildcard spot. How worried should Panthers fans be?Next, the guys play Fill In The Blank, predicting Jason Robertson's next contract AAV.Former NHL defenceman Carlo Colaiacovo from First Up on TSN joins the show for The All 32 to break down everything Toronto Maple Leafs. The slumping Leafs sit in the basement of the Eastern Conference and are closer to the Predators than to a wildcard spot. What needs to change in Leaf Land if they want to turn this season around?SHOUTOUT TO OUR SPONSORS!!

Happy Thanksgiving… Thursday, November 27, 2025. Week 48.   Continued from #S10e189…   And the AAV Paper (https://pubmed.ncbi.nlm.nih.gov/40988338/) from #S10e187… https://curesyngap1.org/podcasts/syngap10/clinical-research-ai-dx-nl47-survey-autism-press-6-days-to-register-for-syngap1conf-s10e187/   https://curesyngap1.org/blog/ Issac's story, Transmitter reprint, Scramble 4 write up and JK on #Autism, #MustRead   https://curesyngap1.org/resources/webinars/ 119 - 112 Register for livestream of the conference, AAV from Allen Inst., dos en espanol, Missense, Unlock and Rare-X for ProMMiS.   https://curesyngap1.org/podcasts/syngap1-stories/  A gold mine have you listened to #38, the Virginie Pod, really must listen, she is our leader. https://www.linkedin.com/posts/graglia_syngap1stories-syngap1-syngap1storiesty-activity-7387203351907708928-liNL    CLINICAL TRIAL & GENETIC MEDICINE CORNER Example of Ultragenyx FAST Angelman follow on trial to look at other ages and genotypes, key message, never give up. https://www.linkedin.com/posts/cureangelman_the-global-aurora-study-will-enroll-approximately-activity-7389647402690957312-Bihi Congrats to Novartis on approval of the first Gene Therapy to Cure SMA! https://www.linkedin.com/posts/graglia_sma-fdaapproval-rarediseaseinnovation-activity-7398939783005347840-Ocd_ Remember Spinraza was approved in December 2019.   TODOS Sign up for Citizen Health: https://www.citizen.health/partners/srf USE YOUR ICD-10 F78.A1 #S10e185 https://www.youtube.com/watch?v=dale0NbxDpU Go to CURE SYNGAP1 Conference 2025 Atlanta: https://curesyngap1.org/events/conferences/cure-syngap1-conference-2025-hosted-by-srf/   SOCIAL MATTERS 4,468 LinkedIn.  https://www.linkedin.com/company/curesyngap1/  1,480 YouTube.  https://www.youtube.com/@CureSYNGAP1    11.2k Twitter https://twitter.com/cureSYNGAP1  45k Insta https://www.instagram.com/curesyngap1/    $CAMP stock is at $3.62 on 26 Nov. ‘25 https://www.google.com/finance/beta/quote/CAMP:NASDAQ Episode 190 of #Syngap10 #CureSYNGAP1

Use our code TALKIN10 for 10% off your next SeatGeek order*: https://seatgeek.onelink.me/RrnK/TALKIN10 Sponsored by SeatGeek. *Restrictions apply. Max $20 discountLooking for a refreshing citrusy kick this summer? Grab a Mountain Dew! Find out where at https://www.mountaindew.com/find-dewWhether you're just wanting to test an idea out, or you're getting serious about launching your own brand, it's never been easier to get started on https://shopify.com/talkinCheck out the newest JM channel, That's Cricket: https://www.youtube.com/ ⁨@thatscricketjm⁩   Coach Trev and Talkin' Jake break down the upcoming pitchers free agency, who will get the long term contracts, what Japanese pitcher Tatsuya Imai can get this off-season and more! 0:00: Intro5:15 Framber Valdez?7:30 Dylan Cease9:45 Ranger Suarez12:30 How long will these FA contracts be vs AAV?18:15Michael King, Brandon Woodruff21:45 Tastuya Imai27:45: Shane Bieber opts in35:00 Shota Imanaga opts out42:15 Zach Littel, Merril Kelly, Chris Bassitt45:00 Lucas Giolito46:00 Dustin May51:15 Relief pitching market53:45 Who has the most need for a closer?56:15 One reliever FA pick? Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

In this episode, Jonah & JP talk about the Sabres getting over .500 for the first time in almost a year. They discuss the playoff race, the goaltending situation, Owen Power, the Alex Tuch contract, and so much more!(0:00) Intro(0:32) World Series Talk(7:33) Sabres are above .500(20:16) Ukko-Pekka Luukkonen & the goalies(48:06) Michael Kesselring Debut // Defense Group(1:02:20) Is the offense legit?(1:15:13) The Owen Power Hate(1:36:16) How to fix the Power Play(1:46:30) Current lineup thoughts (2:02:30) Christian calls in!(2:08:03) Alex Tuch to receive $11.5 million AAV?(2:29:57) Weekly Preview(2:48:18) Best comments of the week(2:54:15) Stretching the runtime to 3 hours(3:02:25) Closing

Gene therapy isn't science fiction anymore, it's becoming one of the most exciting frontiers in diabetes care. In this episode, Dr. Jeremy Pettus and Dr. Steve Edelman sit down with Dr. Fraser Wright, career gene therapist and Co-Founder/Chief Gene Therapy Officer at Kriya Therapeutics, to explore how gene therapy could one day help the body make its own insulin.Together, they unpack what gene therapy actually is, Dr. P's involvement as a medical consultant for Kriya Therapeutics, how AAV (adeno-associated virus) vectors work, and what makes this “one-and-done” approach so different from traditional treatments. From success stories in blindness and hemophilia to emerging type 1 diabetes studies, the trio breaks down the science, the safety, and the hope behind this revolutionary research.You'll learn how gene therapy has moved from rare diseases to more common ones, why the first human trials in diabetes are on the horizon, and what and what this could mean for long-term blood sugar control and independence from injections.Key Topics:Gene Therapy 101: How gene therapy differs from protein-based drugs like insulin, and why AAV vectors act as safe, engineered delivery vehicles rather than infectious viruses.Why AAV, Why Now: Seven FDA-approved AAV-based therapies have proven the potential of long-term, single-dose treatments.From Eyes to Endocrine: Lessons learned from retinal gene therapy are now guiding approaches to metabolic conditions like diabetes.The Type 1 Diabetes Approach: A muscle-targeted program aims to help the body naturally produce insulin and stabilize blood sugar levels.Control and Safety: Built-in glucose sensing and the ability to turn off gene expression ensure precision and reversibility.Real-World Considerations: How exercise, treatment site, and existing technologies like pumps or CGMs could work alongside this therapy.0:00 – Intro: Jeremy and Steve introduce gene therapy and why this topic is a game-changer2:15 – What gene therapy is and how it's different from standard protein-based treatments4:54 – Understanding AAV: safety, engineering, and why it's the preferred delivery method8:50 – Real-world success: seven FDA-approved AAV therapies for genetic diseases12:20 – Lessons learned from treating blindness and how they apply to diabetes17:40 – The Type 1 Diabetes model: using muscle tissue to produce insulin22:15 – Managing control, glucose sensing, and preventing hypoglycemia25:50 – Safety measures and how treatment can be reversed locally if needed28:30 – Exercise, durability, and what animal studies reveal about real-life performance31:10 – Timelines, trials, and what's next for gene therapy in diabetes. What's Ahead: Clinical trials expected to begin around 2026, offering cautious but real optimism for the future of diabetes treatment.Visit TCOYD's Website for more diabetes edutainment for people living with diabetes: tcoyd.org**Tune in for two new episodes each month! Like what you hear and want to help us grow? Please rate and review this podcast so we can reach more people living with diabetes!**Follow our social media channels to empower yourself with the essential areas of diabetes knowledge led by two endocrinologists living with type 1 diabetes: Facebook  |  Instagram  |  YouTube ★ Support this podcast ★

Next-generation platforms and technologies are getting closer to cracking one of biopharma's biggest problems: delivering medicines, and mAbs in particular, to the brain. On the latest BioCentury This Week podcast, BioCentury's Selina Koch details the latest innovations in blood-brain-barrier shuttles and how the technologies could transform the treatment of neurological diseases.BioCentury's Lauren Martz discusses her conversation with Tony Wood, CSO of GSK, which included the pharma's strategy for indication expansion, why it prefers RNA modalities over AAV-based gene therapies, and how its quest for causal biology has evolved over the years.Washington Editor Steve Usdin discusses the first set of FDA's new commissioner's national priority review vouchers, and why the voucher program is unlikely to function as an incentive capable of steering future behavior. Usdin also discusses the potential impact of FDA staffing reductions on the sector. This episode of BioCentury This Week is sponsored by Evotec.View full story: https://www.biocentury.com/article/657326#BloodBrainBarrier #Neurology #DrugDelivery #MonoclonalAntibodies #RNAtherapeutics #CausalBiology #FDA00:01 - Sponsor Message: Evotec01:57 - Brain Shuttles13:57 - GSK Q&A20:08 - FDA VouchersTo submit a question to BioCentury's editors, email the BioCentury This Week team at podcasts@biocentury.com.Reach us by sending a text

WWP NIGHT w/ the DETROIT RED WINGS (Nov. 15th vs. BUF) TICKETS:  https://www.gofevo.com/event/WingedWheelPodcast11-15 WWP NIGHT w/ the GRAND RAPIDS GRIFFINS TICKETS ON SALE NOW: https://griffinshockey.com/wwp The Detroit Red Wings preseason is over, and the kids are still here - is this the most optimistic preseason outlook in Winged Wheel Podcast history? (00:00) Tune in as we start by discussing Michael Brandsegg-Nygard's Detroit Red Wings & NHL-leading performance, how his game compares to Marco Kasper's, whether he could be a long-term solution for Todd McLellan next to Dylan Larkin & Lucas Raymond, & his chances of making the team (6:55). Next, what Justin Holl & Erik Gustafsson being waived mean for Axel Sandin Pellikka's roster chances, how his path compares to Moritz Seider & Simon Edvinsson's, if he's destined to be paired with Albert Johansson, & how the Grand Rapids Griffins AHL path could benefit him like it did Nate Danielson & other prospects (14:30). Finally, Emmitt Finnie's standout preseason & how he took the step past guys like Carter Mazur, Amadeus Lombardi, & Carter Bear, & what his roster chances are in McLellan and Steve Yzerman's eyes (28:20) before we give our full Detroit Red Wings Opening Night roster projections (40:10). After that, our Atlantic Division Preview, including Pastrnak's Boston Bruins, Dahlin's Buffalo Sabres, Raymond's Detroit Red Wings, Hutson's Montreal Canadiens, Tkachuk's Ottawa Senators, Kucherov's Tampa Bay Lightning, Barkov's Florida Panthers, and Matthews' Toronto Maple Leafs (52:30). We wrap up with a look at Jackson LaCombe & Luke Hughes' $9 million AAV contracts and what that means for Steve Yzerman as he looks to extend Simon Edvinsson (1:25:00). All of that & lots more before we take your questions and comments in our Overtime segment (1:30:00) - enjoy! Head over to wingedwheelpodcast.com to find all the ways to listen, how to support the show, and so much more! This episode is brought to you by Green Light Lending: gogreenlightlending.com #ad Support the Jamie Daniels Foundation through Wings Money on the Board: https://www.wingedwheelpodcast.com/wingsmotb

Nick Kypreos, Justin Bourne and Sam McKee start the week reacting to the big news out of Edmonton that Connor McDavid has signed to a two-year, 12.5 AAV extension. They break down the team-friendly deal, the Oilers' next steps, and how McDavid's deal impacts other extension-eligible stars. Then they discuss the Leafs' weekend roster moves, waiving Michael Pezzetta and claiming Sammy Blais and Cayden Primeau. Later, NHL commissioner Gary Bettman joins the show (27:52) to discuss McDavid's contract, Sportico's recent franchise evaluations, the Penguins' potential ownership sale, the league's approach to further expansion, preseason feistiness, complaints about state taxes, and much more.The views and opinions expressed in this podcast are those of the hosts and guests and do not necessarily reflect the position of Rogers Sports & Media or any affiliates.

Nick Kypreos, Justin Bourne and Sam McKee react to more contract movement around the league, with Niko Mikkola signing an 8-year, $40M extension to stay in Florida, and the Ducks locking in young defenceman Jackson LaCombe to an 8-year deal carrying an AAV of $9M. MSG analyst and CEO of Clear Sight Analytics Steve Valiquette (4:41) weighs in on the deals, the immense pressure on today's goalies, Anthony Stolarz's team-friendly extension, the top five netminders over the last three years, and much more. Then, Vally introduces a new game for his weekly appearances: Grill the Panel! Later, Nick, Justin and Sam discuss the NHL franchise value rankings ahead of the start of the season. The views and opinions expressed in this podcast are those of the hosts and guests and do not necessarily reflect the position of Rogers Sports & Media or any affiliates.

Dr. Nicole Paulk is the CEO, Founder, and President of Siren Biotechnology and has dedicated her career to advancing the field of gene therapy. With nearly two decades of expertise, Nicole has been at the forefront of developing cutting-edge advances to propel the field of gene therapy forward for a wide range of diseases. Nicole has held various leadership positions in academia and industry and most notably was an Assistant Professor of AAV Gene Therapy in the UCSF Department of Biochemistry & Biophysics before leaving to found Siren. Nicole has a B.S. in Medical Microbiology, a Ph.D. in Viral Gene Therapy and Regenerative Medicine from OHSU and completed her Postdoctoral Fellowship and Instructorship in Human Gene Therapy at Stanford University prior to starting her lab at UCSF. Nicole is a pioneer in the development of next-generation AAV platforms for gene repair, gene transfer and gene editing, directed evolution for novel engineered capsid evolution, and comparative multi-omic approaches to interrogate translational AAV biology.

Friday, September 26, 2025. Week 39.   DSC has announced! DSC (part of RDCRN, part of NCATS, part of NIH) also announced and continues to raise profile of SYNGAP1 Related Disorders (SRD) Key post https://www.linkedin.com/posts/curesyngap1_86-million-nih-grant-renews-support-for-activity-7373870761230589952-aV1M #RDCRN List with #DSC https://ncats.nih.gov/research/research-activities/rdcrn/consortia   In addition to that, the DSC was formally announced, and will result in five years of SYNGAP1 securing a spot on the map.  This was because of an SRF grant years ago!  Grant https://curesyngap1.org/blog/syngap-research-fund-announces-308-000-multidisciplinary-biomarker-grant-to-boston-childrens-hospital/   Pubmed is at 44! (+2 v ‘23, -10 v ‘24, 2nd place) https://pubmed.ncbi.nlm.nih.gov/?term=syngap1&filter=years.2025-2025&timeline=expanded&sort=date&sort_order=asc   Cell Paper on AAV in Mice: https://www.linkedin.com/posts/boaz-levi-07387741_aav-delivery-of-full-length-syngap1-rescues-activity-7376306391537532928-iT9u   Last week was a CB Conf in Nashville, attended by KAH and VA, thank you to both.  KAH in Staff yesterday, the hardest thing is not seeing Joey.  ☹️  Thanks to MS for going too. MS https://www.linkedin.com/posts/melissasmith1_raredisease-patientadvocacy-syngap1-activity-7374408667091333120-Udp0/ KAH https://www.linkedin.com/posts/kathryn-syngap-research-fund_the-combinedbrain-conference-in-nashville-activity-7374639535021928448-gWB4   Two big upcoming events: Scramble in SC on October 4th https://www.linkedin.com/posts/julie-miles-4294322ba_scramble-for-syngap-activity-7370558331611971585-iw0A   CURE SYNGAP1 Conference 2025 in Atlanta https://curesyngap1.org/events/conferences/cure-syngap1-conference-2025-hosted-by-srf/   SOCIAL MATTERS - 4,371 LinkedIn.  https://www.linkedin.com/company/curesyngap1/ - 1,440 YouTube.  https://www.youtube.com/@CureSYNGAP1 - 11,292 Twitter https://twitter.com/cureSYNGAP1 - 45k Insta https://www.instagram.com/curesyngap1/   COMPANIES WITH NAMED ASSETS FOR SYNGAP1 $CAMP $3.00 at close on 9/23   Episode 184 of #Syngap10 #CureSYNGAP1 #Advocate #PatientAdvocacy #UnmetNeed #SYNGAP1 #SynGAP #SynGAProMMiS

Friday, September 26, 2025. Week 39.   In this episode of Syngap10, we continue the conversation from Episode 183, sharing the latest milestones and moments with our SYNGAP1 community.   DSC has announced! DSC (part of RDCRN, part of NCATS, part of NIH) also announced and continues to raise profile of SYNGAP1 Related Disorders (SRD) Key post https://www.linkedin.com/posts/curesyngap1_86-million-nih-grant-renews-support-for-activity-7373870761230589952-aV1M #RDCRN List with #DSC https://ncats.nih.gov/research/research-activities/rdcrn/consortia   In addition to that, the DSC was formally announced, and will result in five years of SYNGAP1 securing a spot on the map.  This was because of an SRF grant years ago!  Grant https://curesyngap1.org/blog/syngap-research-fund-announces-308-000-multidisciplinary-biomarker-grant-to-boston-childrens-hospital/   Pubmed is at 44! (+2 v ‘23, -10 v ‘24, 2nd place) https://pubmed.ncbi.nlm.nih.gov/?term=syngap1&filter=years.2025-2025&timeline=expanded&sort=date&sort_order=asc   Cell Paper on AAV in Mice: https://www.linkedin.com/posts/boaz-levi-07387741_aav-delivery-of-full-length-syngap1-rescues-activity-7376306391537532928-iT9u    Last week was a CB Conf in Nashville, attended by KAH and VA, thank you to both.  KAH in Staff yesterday, the hardest thing is not seeing Joey.  ☹️  Thanks to MS for going too. MS https://www.linkedin.com/posts/melissasmith1_raredisease-patientadvocacy-syngap1-activity-7374408667091333120-Udp0/ KAH https://www.linkedin.com/posts/kathryn-syngap-research-fund_the-combinedbrain-conference-in-nashville-activity-7374639535021928448-gWB4    Two big upcoming events: Scramble in SC on October 4th https://www.linkedin.com/posts/julie-miles-4294322ba_scramble-for-syngap-activity-7370558331611971585-iw0A    CURE SYNGAP1 Conference 2025 in Atlanta https://curesyngap1.org/events/conferences/cure-syngap1-conference-2025-hosted-by-srf/   SOCIAL MATTERS - 4,371 LinkedIn.  https://www.linkedin.com/company/curesyngap1/  - 1,440 YouTube.  https://www.youtube.com/@CureSYNGAP1    - 11,292 Twitter https://twitter.com/cureSYNGAP1  - 45k Insta https://www.instagram.com/curesyngap1/    COMPANIES WITH NAMED ASSETS FOR SYNGAP1 $CAMP $3.00 at close on 9/23   Episode 184 of #Syngap10 #CureSYNGAP1 #Advocate #PatientAdvocacy #UnmetNeed #SYNGAP1 #SynGAP #SynGAProMMiS

It's Friday afternoon, which means a fresh episode of Oilersnation Radio is ready to massage your eardrums with an hour of off-season Oilers talk. On today's podcast, the fellas discussed the Oilers' roster at training camp, line combos, and much more.We kicked off the Friday episode of ONR with a delicious debate about which forwards could be on the outside looking in when the pre-season wraps in just under two weeks. Whether it's David Tomasek, Curtis Lazar, or Mattias Janmark, there aren't actually that many names to choose from when it comes to the tweeners. As you'll hear, the boys don't necessarily know who will be the odd man out, but what's clear is that everyone was thinking the same thing.Changing gears, the guys looked at the Vasily Podkolzin contract extension and whether it was a bold bet for the Oilers to make on a player who had eight goals. While the $2.95 million AAV may have been surprising to some parts of the fanbase, given that he showed limited offence in his first campaign in Edmonton. Is there more offence there? Is he just what he is? With four years left in Edmonton, including this final year of his current deal, we have a lot of time to find out. Finally, we wrapped up the Friday episode of ONR with another round of Ask the Idiots, betting talk for our friends at bet365, and Hot and Cold Performers to look back on the week. With only weeks left to wait until the start of the 2025-26 season, the guys spent the bulk of the Friday episode discussing a range of topics, some related to the Oilers and others not, but that's what happens before training camps kick off. Hosted on Acast. See acast.com/privacy for more information.