DeCure for Facioscapulohumeral muscular dystrophy 4, digenic
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for facioscapulohumeral muscular dystrophy 4, digenic — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFacioscapulohumeral muscular dystrophy 4, digenic maps to a 2-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 facioscapulohumeral muscular dystrophy 4, digenic 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
DNA methyltransferase 3 beta (DNMT3B) — DNMT3B 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 sahdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6PA7 · 2.94 Å · ligand S-ADENOSYL-L-HOMOCYSTEINE (SAH). Experimental structure, not a prediction.
What the evidence adds up to
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder of skeletal muscle, affecting the face, shoulders and upper arms, and is the third most common genetic degenerative disorder of skeletal muscle. The underlying cause is now understood to be a toxic gain-of-function from de-repression of the DUX4 gene, which is not normally expressed in skeletal muscle. This consensus on the molecular mechanism has, for the first time, allowed a targeted approach to treatment, and there is increasing interest in drug development for FSHD, buoyed by recent therapeutic successes in other neuromuscular diseases. No specific drug is named in these abstracts as having been tested in FSHD.
At present there is no cure for the disease. Management strategies are available to improve quality of life and prevent further degeneration of muscle groups, including both lifestyle and medical intervention. The broader field of pharmacological therapies for the muscular dystrophies continues to advance steadily, with research exploring strategies from symptomatic management to mutation-specific approaches that attempt to correct the root cause. Some of these advances have already led to clinical trials in the dystrophinopathies and limb-girdle dystrophies, but no completed clinical trials for FSHD are reported in these abstracts.
No concrete numbers for survival, response rates, or sample sizes are provided in any of these abstracts. The 2020 review notes that the field is still in the stage of planning and executing future clinical trials, and the 2019 review states there is no cure. What remains missing are completed clinical trials with reported outcomes, validated biomarkers for patient stratification, and the funding necessary to move from the identified target (DUX4 de-repression) to a tested pharmacological agent in FSHD patients.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Seminars in Neurology · 2012 · 71 citations
The Muscular Dystrophies
AbstractThe muscular dystrophies are disorders of progressive muscular degeneration and weakness. As a group they display clinical heterogeneity that reflects the heterogeneity of molecular mechanisms responsible for them, and range from congenital to adulthood onset. Recent advances in the field include improved methods of diagnosis, continued identification of disease genes, and the development of a unified model of pathogenesis in facioscapulohumeral dystrophy. These advances are reflected in the development of new therapeutic approaches, some of which have already led to clinical trials in the dystrophinopathies and limb-girdle dystrophies.
Journal of Neuromuscular Diseases · 2020 · 39 citations · open access
Current Therapeutic Approaches in FSHD
AbstractFacioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies. Over the last decade, a consensus was reached regarding the underlying cause of FSHD allowing-for the first time-a targeted approach to treatment. FSHD is the result of a toxic gain-of-function from de-repression of the DUX4 gene, a gene not normally expressed in skeletal muscle. With a clear therapeutic target, there is increasing interest in drug development for FSHD, an interest buoyed by the recent therapeutic successes in other neuromuscular diseases. Herein, we review the underlying disease mechanism, potential therapeutic approaches as well as the state of trial readiness in the planning and execution of future clinical trials in FSHD.
Current Opinion in Neurology · 2012 · 24 citations
Pharmacological therapies for muscular dystrophies
AbstractPURPOSE OF REVIEW: The study reviews recent advances in pharmacological management of muscular dystrophies. Similarities and differences among the pathophysiology of different forms of muscular dystrophy lead to a broad array of approaches to provide new treatments. RECENT FINDINGS: In this review, we include only those muscular dystrophies for which advances have been published in the past year. This represents the 'advancing edge' of a large body of research over more than 20 years. This runs the gamut of new discoveries in symptomatic management to mutation-specific strategies that attempt to correct the root cause of the disorder. SUMMARY: The field of pharmacological therapies for the muscular dystrophies continues to steadily advance. It is encouraging that research into new therapies is increasingly exploring pharmacological strategies with the potential to ameliorate disease pathology to a clinically significant degree.
Intractable & Rare Diseases Research · 2019 · 16 citations · open access
Management strategies in facioscapulohumeral muscular dystrophy
AbstractFacioscapulohumeral muscular dystrophy (FSHD) also known as Landouzy-Dejerine disease, is an autosomal-dominant disorder of the skeletal muscles with the name according to the various muscle groups it affects: the face, shoulders and upper arms. It is the third most common genetic degenerative disorder of the skeletal muscles without specific patterns in all the affected individuals. At present there is no cure for the disease but numerous management strategies are available to improve the quality of life and prevent further degeneration of various muscle groups. This review aims to provide an insight on the management strategies for FSHD patients including both lifestyle and medical intervention.
Dialnet (Universidad de la Rioja) · 1997 · 0 citations
Contra el monopolio de Dios: reflexiones de un buscador descreído
AbstractFacioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies. Over the last decade, a consensus was reached regarding the underlying cause of FSHD allowing-for the first time-a targeted approach to treatment. FSHD is the result of a toxic gain-of-function from de-repression of the DUX4 gene, a gene not normally expressed in skeletal muscle. With a clear therapeutic target, there is increasing interest in drug development for FSHD, an interest buoyed by the recent therapeutic successes in other neuromuscular diseases. Herein, we review the underlying disease mechanism, potential therapeutic approaches as well as the state of trial readiness in the planning and execution of future clinical trials in FSHD.
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.
