Stuart Cook
@stuartacook1
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MD PhD. Targeting regeneration and ageing. Founder Enleofen and VVB Bio. Views my own.
UK or Singapore, depends
Joined September 2015
Slowing ageing and increasing health-span with anti-IL11 therapy. A 20 min video
www.youtube.com
The Aging and Drug Discovery Conference (ARDD) 2022 is pleased to present Stuart Cook from The Duke-NUS Medical School With the talk The IL-11/ERK/mTOR axis ...
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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.
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Therapeutic (small molecule) inhibition of global gp130 signaling improves right ventricular function in a pig model of RV loading. PAH in humans next?. 🙌
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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! 🤗
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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
For idiopathic pulmonary fibrosis (IPF), interleukin 11 (IL-11) is a pivotal cytokine that stimulates the transformation of fibroblasts into myofibroblasts, thus accelerating the progression of...
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Bi-specific.Anti-IL11 + Anti-TSLP.Perhaps for asthma?.Field moving fast
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Clever - non-antibody - ways to inhibit IL11 activity using biased agonist-like modalities to treat fibrotic lung disease:. And.
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Nice.As predicted:.
pubmed.ncbi.nlm.nih.gov
Recent studies have shown IL11 to be pro-fibrotic, pro-inflammatory and anti-regenerative in heart, liver, lung and kidney disease in mice and humans. However, data also show that IL11 is specifica...
We are happy to share our new paper. We identified il11 as a regenerative factor to stimulate heart regeneration. However, prolonged il11 treatment causes fibrosis due to persistent activation of the epicardium.
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🙌.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
AbstractAims. Interleukin 11 (IL11) was initially thought important for platelet production, which led to recombinant IL11 being developed as a drug to tre
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Timely reminder that the IL-6 (IL-11) trans-signalling idea/field is likely based on an experimental artefact.
pubmed.ncbi.nlm.nih.gov
IL6 is a proinflammatory cytokine that binds to membrane-bound IL6 receptor (IL6R) or soluble IL6R to signal via gp130 in cis or trans, respectively. We tested the hypothesis that sgp130Fc, which is...
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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
www.nature.com
Nature Communications - In interstitial lung disease, aberrant KRT8+ basaloid cells impair alveolar repair mechanisms. Here they show that Interleukin-11 expression in KRT8+ cells potentiates their...
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Nice. Check out the GWAS hits for menopause at the IL11 locus…. Coincidence?.
Systemic low-dose anti-fibrotic treatment attenuates ovarian aging in the mouse.
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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
www.biorxiv.org
Genetic suppression of activity of the insulin/IGF/mTORC1/Ras network can ameliorate the effects of ageing in animals. The network provides multiple drug targets because of its role in metabolic...
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💯 . 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.
Sometimes peer review diminishes the quality of an article. Painful example: the authors had to remove their striking epigenetic clock results from the high profile paper titled "Inhibition of IL-11 Signaling Extends Mammalian Healthspan and Lifespan." Fortunately, the peer.
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RT @ImmunoFever: @stuartacook1 @MartinBJensen @aa_widjaja @metapredict @MitoPsychoBio @KSadtler And to keep these thoughts in one🧵: I reall….
pmc.ncbi.nlm.nih.gov
IL-11 and IL-11 receptor (R)α are induced by Th2 cytokines. However, the role(s) of endogenous IL-11 in antigen-induced Th2 inflammation has not been fully defined. We hypothesized that IL-11,...
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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 Needs investment, build out, approvable endpoints and not easy +++. But faster to humans….
vvb.bio
VVB Bio is a cutting-edge biotechnology company dedicated to transforming lives through innovative antibody therapeutics.
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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 Faster to humans, not another 5 years in mice. Needs investment, build out, approvable endpoints and not easy ++. But. .
vvb.bio
VVB Bio is a cutting-edge biotechnology company dedicated to transforming lives through innovative antibody therapeutics.
💰 Anyone willing to finance a study combining the latest IL11 inhibition intervention — that was just shown to extend lifespan in mice by 25% — with other interventions with the goal of finding synergistic combinations?.
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A very interesting question. My best guess = nerves. In old IL11-EGFP mice there is big signal in skeletal muscle nerve bundles/NMJ (see Supl figs). Recovery of function with anti-IL11 is > muscle mass effect. So I think innervation is important….
@stuartacook1 Any thoughts on the muscle mechanism? I can see from our large human data sets that the most variable IL11RA transcript is the low abundance 390aa variant, with the high signal variant (422aa) largely invariant.
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We did epigenetic clock in the mice. Large effect (++). Reviewer 1 made us take it out (despite our protests - see rebuttal at Nature website). Data is shown in our online talks and on BioRxiv (I think). For sure a biomarker of interest for human trials….
@MartinBJensen @aa_widjaja @stuartacook1 Has anyone done IL-11 infusions and then assessed frailty and/or DNAme clocks?.
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IL11 upregulates PDL1 to promote tumour immune escape. There will be a lot more coming on this. Already heading to clinical trials with Mabwell Therapeutics:.
advanced.onlinelibrary.wiley.com
Increased secretion of IL11 by reactive astrocytes, which binds to EGFR and gp130 on tumor cells and activates the downstream AKT signaling, promotes PDL1 expression in EGFR-mutated NSCLC BM cells...
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