DeCure for Facioscapulohumeral muscular dystrophy 2
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for facioscapulohumeral muscular dystrophy 2 — 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 moduleFacioscapulohumeral muscular dystrophy 2 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 facioscapulohumeral muscular dystrophy 2 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
structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1) — SMCHD1 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 atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6MW7 · 2.194 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
A 2004 Cochrane review found only two published randomised controlled trials for drug treatment in facioscapulohumeral muscular dystrophy. One trial compared creatine supplementation with placebo and showed a non-significant difference in favour of creatine. The other compared high and low-dose albuterol (salbutamol) with placebo and showed no significant difference in muscle strength at one year, although some secondary measures such as lean body mass and handgrip strength did improve. A third unpublished randomised controlled trial of albuterol was identified. The review concluded there is no evidence from randomised controlled trials to support any drug treatment for the condition.
By 2020, a consensus had been reached that FSHD is caused by a toxic gain-of-function from de-repression of the DUX4 gene, a gene not normally expressed in skeletal muscle. This provided a clear therapeutic target for the first time, and the 2020 review noted increasing interest in drug development for FSHD, buoyed by therapeutic successes in other neuromuscular diseases. The review discussed potential therapeutic approaches and the state of trial readiness.
Earlier suggestions that corticosteroids might be helpful were not supported by a subsequent open label study, according to the 2004 review. The 2012 review of muscular dystrophies noted the development of a unified model of pathogenesis in facioscapulohumeral dystrophy and reflected that new therapeutic approaches had already led to clinical trials in the dystrophinopathies and limb-girdle dystrophies, but did not report any specific trial results for FSHD.
What is still missing are adequately powered randomised controlled trials of any drug treatment for FSHD, with muscle strength at one year as the primary outcome. The 2004 review identified only two such trials, and no subsequent trial has changed that conclusion. The identification of DUX4 as a target has not yet produced published randomised controlled trial evidence of efficacy. Money for large-scale trials, trial designs that account for the slow and variable progression of FSHD, and patient stratification by genetic subtype remain absent.
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.
Cochrane Database of Systematic Reviews · 2004 · 39 citations · open access
Drug treatment for facioscapulohumeral muscular dystrophy
AbstractBACKGROUND: Facioscapulohumeral muscular dystrophy is a progressive muscle disease which has no agreed treatment. Early suggestions that corticosteroids might be helpful were not supported by a subsequent open label study. The beta 2 adrenergic agonist albuterol, also known as salbutamol, is known to have anabolic effects which might be beneficial for facioscapulohumeral muscular dystrophy. Creatine has been used as a muscle performance enhancer by athletes and it might be helpful in muscular dystrophies including facioscapulohumeral muscular dystrophy. OBJECTIVES: The objective of the review was to determine whether there is any drug treatment which alters the progression of facioscapulohumeral muscular dystrophy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group specialised register (searched August 2003), MEDLINE (January 1966 to August 2003) and EMBASE (January 1980 to August 2003) for any references to facioscapulohumeral muscular dystrophy. Abstracts from the major neurological meetings and trial bibliographies were also searched for further references to trials. Experts were contacted for information regarding unpublished trials or trials in progress. SELECTION CRITERIA: We included all randomised or quasi-randomised trials of any drug treatment for facioscapulohumeral muscular dystrophy, in adults with a recognised diagnosis of facioscapulohumeral muscular dystrophy. Trials had to include an assessment of muscle strength at one year. DATA COLLECTION AND ANALYSIS: All identified trials were independently assessed by both reviewers to ensure that they fulfilled the selection criteria and were then rated for their quality. Trial data were extracted and entered by one reviewer and checked by the other. If appropriate data existed a weighted treatment effect was to be calculated across trials using the Cochrane statistical package, Review Manager. The results were to have been expressed as relative risks and 95% confidence intervals and risk differences and 95% confidence intervals for dichotomous outcomes, and weighted mean differences and 95% confidence intervals for continuous outcomes. MAIN RESULTS: Two published high quality randomised controlled trials fulfilled the selection criteria. One compared creatine supplementation with placebo and the other compared high and low-dose albuterol with placebo. A further unpublished randomised controlled trial of albuterol in facioscapulohumeral muscular dystrophy was identified. The creatine trial showed a non-significant difference in favour of creatine. The albuterol trial showed no significant difference in muscle strength at one year but some secondary measures such as lean body mass and handgrip strength did improve. REVIEWERS' CONCLUSIONS: There is no evidence from randomised controlled trials to support any drug treatment for facioscapulohumeral muscular dystrophy but only two randomised controlled trials have been published.
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.
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.
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