DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for myostatin-related muscle hypertrophy — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMyostatin-related muscle hypertrophy maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for myostatin-related muscle hypertrophy is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
myostatin (MSTN) — MSTN is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6UMX · 2.79 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Myostatin was identified in 1997 as a negative regulator of muscle growth. A 2004 review states that an antimyostatin monoclonal antibody (JA16) increased muscle mass in healthy older mice and muscle function in postnatal mdx mice. A 2008 review notes that decreasing myostatin levels or inhibiting its function can dramatically increase muscle size in both humans and animals, but adds that a growing body of evidence suggests such increases may not translate into improved athletic performance.
A 2021 review reports that preclinical studies have shown potential for increasing muscular mass and ameliorating pathological features of dystrophic muscle by inhibiting myostatin in various ways. However, hardly any clinical trials have proven to translate the promising results from animal models into patient populations. Another 2021 review states that myostatin null mice exhibit skeletal muscle fibre hyperplasia and hypertrophy, and myostatin deficiency in larger mammals like sheep and pigs engenders muscle fibre hyperplasia. It also reports that pharmacological inhibition of myostatin directly or via decoy receptors has revealed improvements in muscle and bone properties in mouse models of osteogenesis imperfecta, osteoporosis, osteoarthritis, Duchenne muscular dystrophy, and diabetes. The same review notes recent disappointing clinical trial outcomes of induced myostatin inhibition in diseases with significant neuromuscular wasting and atrophy.
The 2021 review on limited success states that the clinical relevance of future antimyostatin treatment should be put into perspective. The 2008 review raises concern that myostatin inhibitors may be among the next generation of ergogenic pharmaceuticals or gene doping technology. What is still missing is a clear understanding of why translation from animal models to patients is difficult, and the complexity of myostatin regulation that requires further clarification. No adequately powered, well-designed clinical trials have yet shown benefit in human muscle hypertrophy conditions, and patient stratification strategies remain unexplored.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Clinical Nutrition & Metabolic Care · 2004 · 58 citations
Myostatin: a therapeutic target for skeletal muscle wasting
AbstractPURPOSE OF REVIEW: This review discusses recent developments in myostatin research, focusing on the basic actions of myostatin on skeletal muscle, the identification of key regulatory elements of the myostatin pathway, and the promise of myostatin as a therapeutic target in muscle-related disorders. RECENT FINDINGS: In addition to a well-characterized role in muscle development, recent research advances have solidified the importance of myostatin in adult muscle, although questions remain. A number of possible regulatory proteins for myostatin have been identified, showing a complex picture of myostatin regulation that requires clarification. The identification of an antimyostatin monoclonal antibody (JA16) shows the promise of myostatin as a target for muscle-wasting disorders; the antibody has already been shown to increase muscle mass in healthy older mice and muscle function in postnatal mdx mice. SUMMARY: Since its discovery in 1997, myostatin has quickly been established as a key regulator of skeletal muscle mass. Recent developments strengthen the idea that myostatin will be an important therapeutic target for muscle-wasting-related disorders, and as more details of myostatin regulation and its mechanisms of action are clarified, myostatin will continue to dominate the skeletal muscle development and muscle-wasting literature.
Antimyostatin Treatment in Health and Disease: The Story of Great Expectations and Limited Success
AbstractIn the past 20 years, myostatin, a negative regulator of muscle mass, has attracted attention as a potential therapeutic target in muscular dystrophies and other conditions. Preclinical studies have shown potential for increasing muscular mass and ameliorating the pathological features of dystrophic muscle by the inhibition of myostatin in various ways. However, hardly any clinical trials have proven to translate the promising results from the animal models into patient populations. We present the background for myostatin regulation, clinical and preclinical results and discuss why translation from animal models to patients is difficult. Based on this, we put the clinical relevance of future antimyostatin treatment into perspective.
Scandinavian Journal of Medicine and Science in Sports · 2008 · 49 citations
Myostatin inhibition: a potential performance enhancement strategy?
AbstractA decade has passed since myostatin was first identified as a negative regulator of muscle growth. Since then, studies in both humans and animals have demonstrated that decreasing the levels of this growth factor or inhibiting its function can dramatically increase muscle size, and a number of therapeutic applications of myostatin inhibition to the treatment of myopathies and muscle atrophy have been proposed. As such treatments would be likely to also stimulate muscle growth in healthy individuals, there is a growing concern among anti-doping authorities that myostatin inhibitors may be among the next generation of ergogenic pharmaceuticals or even in the vanguard of "gene doping" technology. While the ability to stimulate muscle growth through myostatin inhibition is well documented, a growing body of evidence suggests such increases may not translate into an improvement in athletic performance. This article briefly reviews the function of this potent regulator of muscle development and explores the potential therapeutic uses, and potential ergogenic abuses, of myostatin manipulation.
Frontiers in Genetics · 2021 · 30 citations · open access
Deciphering Myostatin’s Regulatory, Metabolic, and Developmental Influence in Skeletal Diseases
AbstractCurrent research findings in humans and other mammalian and non-mammalian species support the potent regulatory role of myostatin in the morphology and function of muscle as well as cellular differentiation and metabolism, with real-life implications in agricultural meat production and human disease. Myostatin null mice ( mstn −/− ) exhibit skeletal muscle fiber hyperplasia and hypertrophy whereas myostatin deficiency in larger mammals like sheep and pigs engender muscle fiber hyperplasia. Myostatin’s impact extends beyond muscles, with alterations in myostatin present in the pathophysiology of myocardial infarctions, inflammation, insulin resistance, diabetes, aging, cancer cachexia, and musculoskeletal disease. In this review, we explore myostatin’s role in skeletal integrity and bone cell biology either due to direct biochemical signaling or indirect mechanisms of mechanotransduction. In vitro , myostatin inhibits osteoblast differentiation and stimulates osteoclast activity in a dose-dependent manner. Mice deficient in myostatin also have decreased osteoclast numbers, increased cortical thickness, cortical tissue mineral density in the tibia, and increased vertebral bone mineral density. Further, we explore the implications of these biochemical and biomechanical influences of myostatin signaling in the pathophysiology of human disorders that involve musculoskeletal degeneration. The pharmacological inhibition of myostatin directly or via decoy receptors has revealed improvements in muscle and bone properties in mouse models of osteogenesis imperfecta, osteoporosis, osteoarthritis, Duchenne muscular dystrophy, and diabetes. However, recent disappointing clinical trial outcomes of induced myostatin inhibition in diseases with significant neuromuscular wasting and atrophy reiterate complexity and further need for exploration of the translational application of myostatin inhibition in humans.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
