Stuart Cook

Slowing ageing and increasing health-span with anti-IL11 therapy A 20 min video m.youtube.com/watch?v=oNc5Mx…

Met an “I’m a biotech” guy today. Introduced himself as a ‘serial C-suite’ chap. I thought, what a complete zero-value-add arse. And he was. They mostly are.

Therapeutic (small molecule) inhibition of global gp130 signaling improves right ventricular function in a pig model of RV loading. PAH in humans next? 🙌 scholar.google.com.sg/scholar_url?ur…

Wonderful leaving dinner with Imperial friends and colleagues last night. Thank you for the kind words and the lovely present, which will be put to very good use! 🤗

Now perhaps the most replicated target gene for lung fibrosis in multiple POC studies Four clinical trials in progress: NCT05331300 NCT05658107 NCT05740475 NCT06612970 All began with PMID: 31554736, just 6 years ago 🚀 pubmed.ncbi.nlm.nih.gov/39791575/

Bi-specific Anti-IL11 + Anti-TSLP Perhaps for asthma? Field moving fast clinicaltrials.gov/study/NCT06612…

Clever - non-antibody - ways to inhibit IL11 activity using biased agonist-like modalities to treat fibrotic lung disease: sciencedirect.com/science/articl… And sciencedirect.com/science/articl…

Nice As predicted: pubmed.ncbi.nlm.nih.gov/36629985/

🙌 IL11 is directly toxic in cardiac myocytes causing calcium handling disturbance and impaired contraction Negatively inotropic in vivo Not just a fibroblast factor Heart failure target? 🤨 academic.oup.com/cardiovascres/…

Timely reminder that the IL-6 (IL-11) trans-signalling idea/field is likely based on an experimental artefact pubmed.ncbi.nlm.nih.gov/38338642/

@TheBHF @DrDeclanORegan @imperialcollege @ImperialMed Whoop! The best.

We’re delighted to announce @DrDeclanORegan from @ImperialCollege as the first BHF Professor of Cardiovascular AI. Declan’s cutting-edge research will use AI technology to understand more about how our genes and environment affect our hearts. bhf.org.uk/what-we-do/our… @ImperialMed @ImperialNHLI @MRC_LMS

Pssst - its not just IL11 effects on fibroblasts: “These data show that IL11 inhibits reparative AT2-to-AT1 differentiation in the damaged lung to limit endogenous alveolar regeneration, resulting in fibrotic lung disease” Damaging EMT, as seen in kidney nature.com/articles/s4146…

Nice. Check out the GWAS hits for menopause at the IL11 locus… Coincidence?

Trametinib common side effects (BNF): Abdominal pain; anaemia; constipation; cough; dehydration; diarrhoea; dry mouth; fever; haemorrhage; hypersensitivity; infection; intracranial haemorrhage; lymphoedema; nausea; dyspnea; stomatitis; vomiting, etc biorxiv.org/content/10.110…

💯 We wanted to keep in the clock data, even if pushed to the supplement. We appealed to both the reviewer and [separately] the editor. If something is truly ‘anti-ageing’ it should affect epigenetic clock, across tissues. I think it should be a standard biomarker.

@stuartacook1 @MartinBJensen @aa_widjaja @metapredict @MitoPsychoBio @KSadtler And to keep these thoughts in one🧵: I really think this exciting new understanding of the impacts of IL-11 signaling will help us better understand how Th2-type responses could drive #IACI. There's much metabolic overlap between these illnesses and aging. ncbi.nlm.nih.gov/pmc/articles/P…

@ydeigin @elonmusk Maybe he could fund some clinical trials! Boy does the field need some help.

Sounds like @elonmusk might finally prefer “some life extension thing” to being dead?🤔

@ydeigin @PeterDiamandis @SergeyYoung200 @hevolution_f @yurimilner @JeffBezos @sama @brian_armstrong @apollohealthvc Like it! Needs a visionary person, institution, consortium or even government to fund a pivotal trial. Think non-conventional team = best chance. Trial design is hard. Small, fundable and approvable, try sarcopenia? Go all out = TAME-like (funding +++)?

Paging longevity investors! IL11 inhibition extended lifespan in mice 25% — @stuartacook1 is ready to take it to the clinic. @PeterDiamandis @SergeyYoung200 @hevolution_f @yurimilner @JeffBezos @sama @brian_armstrong @apollohealthvc

It is suggested we do more [5 year] mice studies but how about a human trial? We have an anti-IL11 therapy specifically engineered for human ageing trials at vvb.bio. Needs investment, build out, approvable endpoints and not easy +++. But faster to humans…

I’ll raise you: How about a clinical trial? We have engineered a super long acting and potent anti-IL11 for human ageing trials at vvb.bio. Faster to humans, not another 5 years in mice Needs investment, build out, approvable endpoints and not easy ++. But..

@ydeigin @theodorus5 @aubreydegrey We did the Il11ra KO for healthspan and saw similar effects. Not X209 - think PK might be an issue as IL11RA widely expressed and so need multiple dosing for longterm. Not ideal for anti-ageing Rx.

@stuartacook1 @theodorus5 @aubreydegrey Hope you do! Btw did you try testing X209 for lifespan/healthspan?

🚨 Want to learn more about the recent explosive longevity study that extended mouse lifespan by 25% via IL11 inhibition? Watch this superb talk by the study’s senior author (@stuartacook1) that includes a nice backstory and some additional results: youtu.be/oNc5MxkWrms