DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for muscular dystrophy — screening already-approved drugs against its 37-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMuscular dystrophy maps to a 37-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 muscular dystrophy 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
choline kinase beta (CHKB) — CHKB 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 2sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3LQ3 · 1.42 Å · ligand (2S)-2-[4'-({dimethyl[2-(phosphonooxy)ethyl]ammonio}acetyl)biphenyl-4-yl]-2-hydroxy-4,4-dimethylmorpholin-4-ium (HC7). Experimental structure, not a prediction.
What the evidence adds up to
In a survey of 170 people with myotonic or facioscapulohumeral muscular dystrophy, fatigue was reported by 91%, imbalance by 82%, and pain by 77%. Fatigue was the most severe symptom, with a mean severity of 5.14 out of 10, followed by imbalance at 4.95. Symptoms were most likely to stay the same or worsen after onset. After controlling for medical and demographic confounds, symptoms accounted for 17% of the variance in mental health, 10% of home competency, 10% of social integration, and 16% of productive activity in myotonic dystrophy type 1, and 12% of productive activity in facioscapulohumeral muscular dystrophy.
A 2012 review of pharmacological therapies for muscular dystrophies noted that the field continues to advance, with research spanning symptomatic management to mutation-specific strategies. The review included only those muscular dystrophies for which advances had been published in the preceding year. A 2018 review of gene and cell therapy stated that several trials were ongoing and more were expected, but that many hurdles remained and it was unclear whether current strategies would overcome them or if further improvements would be needed.
For Duchenne muscular dystrophy specifically, a 2019 review noted that two genetic-based therapeutics had been approved for clinical use but that their efficacy was still very low. The review described drug repurposing as a way to reduce research and development costs for rare diseases, and it summarised the state of clinical trials and preclinical studies for that approach. A 2020 book on muscular dystrophy covered genetics, current therapeutic strategies aimed at ameliorating symptoms and improving quality of life and life expectancy, and considerations for the design of clinical trials.
What remains missing is evidence from adequately powered, randomised controlled trials that demonstrate a clear clinical benefit for any repurposed drug in any form of muscular dystrophy. Patient stratification by genetic subtype, disease stage, and symptom profile has not been systematically applied in most studies. Funding for large, long-term trials that measure functional outcomes rather than surrogate biomarkers is still insufficient.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Physical Medicine & Rehabilitation · 2013 · 25 citations
Symptom Burden in Persons with Myotonic and Facioscapulohumeral Muscular Dystrophy
AbstractOBJECTIVE: This study examines the prevalence of pain, fatigue, imbalance, memory impairment, and vision loss in persons with myotonic and facioscapulohumeral dystrophy and their association with functioning. DESIGN: A survey (N = 170) included measures of severity (0-10 scales) and course of these symptoms as well as measures of social integration, home competency, mental health, and productive activity. Descriptive and regression analyses examined the associations between symptoms and functioning. RESULTS: Fatigue (91%), imbalance (82%), and pain (77%) were the most commonly reported. The most severe symptom was fatigue (mean ± SD severity, 5.14 ± 2.81), followed by imbalance (4.95 ± 3.25). Symptoms were most likely to stay the same or worsen since onset. Controlling for potential medical and demographic confounds, symptoms were associated with 17% of the mental health variance, 10% of home competency, 10% of social integration, 16% of productive activity for myotonic dystrophy type 1, and 12% of productive activity for facioscapulohumeral muscular dystrophy. CONCLUSIONS: Pain, fatigue, and imbalance are common in persons with muscular dystrophy. Interventions may be useful to mitigate their impact on functioning. Further research should examine these relationships to guide clinical practices.
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.
New England Journal of Medicine · 1965 · 24 citations
Ineffective Treatment of Muscular Dystrophy with an Anabolic Steroid and Other Measures
AbstractTHROUGHOUT the years many agents have been tested for their therapeutic benefit in muscular dystrophy, a relentlessly progressive disease. Eventually, all have been found to be ineffective after careful evaluation, including a variety of anabolic hormones.1 2 3 4 5 6 7 8 More recently Dowben9 has presented preliminary evidence that patients with muscular dystrophy showed significant "improvement" when treated by a program consisting of the anabolic steroid, 1-methyl-Δ1 androstenolone acetate,ǁ digitoxin and exercise.The purpose of this report is to re-evaluate such a therapeutic program in muscular dystrophy when the drugs are used singly, in combination and with or without exercise. Objective serial measurements were made . . .
Human Gene Therapy · 2018 · 20 citations · open access
Gene and Cell Therapy for Muscular Dystrophies: Are We Getting There?
AbstractIn the last few years, significant advances have occurred in the preclinical and clinical work toward gene and cell therapy for muscular dystrophy. At the time of this writing, several trials are ongoing and more are expected to start. It is thus a time of expectation, even though many hurdles remain and it is unclear whether they will be overcome with current strategies or if further improvements will be necessary.
International Journal of Molecular Sciences · 2019 · 20 citations · open access
Teaching an Old Molecule New Tricks: Drug Repositioning for Duchenne Muscular Dystrophy
AbstractDuchenne muscular dystrophy (DMD) is one of the most severe forms of inherited muscular dystrophies. The disease is caused by the lack of dystrophin, a structurally essential protein; hence, a definitive cure would necessarily have to pass through some form of gene and/or cell therapy. Cell- and genetic-based therapeutics for DMD have been explored since the 1990s and recently, two of the latter have been approved for clinical use, but their efficacy is still very low. In parallel, there have been great ongoing efforts aimed at targeting the downstream pathogenic effects of dystrophin deficiency using classical pharmacological approaches, with synthetic or biological molecules. However, as it is always the case with rare diseases, R&D costs for new drugs can represent a major hurdle for researchers and patients alike. This problem can be greatly alleviated by experimenting the use of molecules that had originally been developed for different conditions, a process known as drug repurposing or drug repositioning. In this review, we will describe the state of the art of such an approach for DMD, both in the context of clinical trials and pre-clinical studies
Duchenne Muscular Dystrophy: Advances in Therapeutics
AbstractDuchenne Muscular Dystrophy: Advances in Therapeutics
edited by J.S. Chamberlain and T.A. Rando, 450 pp., Taylor and Francis Group, 2006
This timely book has an introduction by A.E.H Emery and is then divided into four sections with individual chapters being written by one or more experts in that field. One of the major strengths of the book is its simple, logical layout. Section I (“Duchenne Muscular Dystrophy Background”) encompasses a clinical overview of DMD, the role of dystrophin and the dystrophin-associated …
ANABOLIC STEROIDS IN THE MANAGEMENT OF MUSCULAR DYSTROPHY
AbstractA group of 21 patients with muscular dystrophy, 17 of them boys with the pseudohypertrophic form, were treated with a regimen including the use of an anabolic steroid, digitoxin, and physical exercise. This program had previously been reported to be efficacious. One year after the initiation of treatment all patients in the present study were significantly worse. None showed any change which could be interpreted as representing improvement. Five boys displayed rather rapid progression of the disease leading to loss of ambulation. Physicians at eight other centers, with experience in trials of identical therapy in approximately 300 patients, report no evidence of any objective benefit from the use of this steroid therapy in muscular dystrophy.
Understanding the beneficial effects of doxycycline on the dystrophic phenotype of the <i>mdx</i> mouse
AbstractINTRODUCTION: The purpose of this study was to better understand the beneficial effects of doxycycline on the dystrophic muscles of the mdx mouse. METHODS: Doxycycline (DOX) was administered for 36 days, starting on postnatal day 0, via drinking water. Untreated mdx mice received plain water for the same period and served as a control group. RESULTS: DOX decreased the levels of metalloproteinase-9 and tumor necrosis factor-alpha in the biceps brachii and diaphragm of the mdx mice. It also reduced the total amount of calcium in the muscles studied, concomitant with an increase in the levels of calsequestrin 1. CONCLUSIONS: The results show that DOX can affect factors that are important in dystrophic pathogenesis and highlight its potential as a readily accessible therapy in clinical trials for treatment of Duchenne muscular dystrophy.
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.
