DeCure for Distal myopathy with anterior tibial onset
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for distal myopathy with anterior tibial onset — 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 moduleDistal myopathy with anterior tibial onset 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 distal myopathy with anterior tibial onset 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.
What the evidence adds up to
The 2003 study of a large Finnish family with distal myopathy identified seven patients showing autosomal dominant inheritance, with onset between 32 and 45 years. First symptoms were hand clumsiness and stumbling from a steppage gait. Weakness began in the small hand muscles, gluteus medius, and both anterior and posterior leg compartments, then progressed to other hand intrinsics, forearm muscles, triceps, infraspinatus, and proximal lower limbs. Asymmetry was common. Electromyography showed myopathic features, serum creatine kinase was normal or slightly elevated, and muscle biopsy showed many rimmed vacuoles and dystrophic changes. No linkage was found to Welander distal myopathy or tibial muscular dystrophy loci. The authors concluded the family might have a distinct distal myopathy and planned a genome-wide scan.
A 2005 review of distal myopathies summarised that recent studies had identified genes and mutations responsible for early onset (Laing) myopathy, tibial (Udd) myopathy, and distal myopathy with rimmed vacuoles (Nonaka). The last was shown to be allelic with quadriceps-sparing hereditary inclusion body myopathy (IBM2). The review noted overlap between distal myopathies, limb-girdle myopathies, and hereditary inclusion body myopathies, and reported new diagnostic approaches using magnetic resonance imaging and a blood-based assay for dysferlin deficiency. No therapies were described.
A 2018 clinical description of inclusion body myositis stated that the disorder typically affects people in their early 60s, with onset before age 40 rare. It is characteristically asymmetrical, with finger flexor involvement (sparing metacarpophalangeal flexors relative to distal finger flexors) and quadriceps involvement, where vastus medialis and lateralis waste disproportionately while rectus femoris is relatively spared, so knee extension is often only mildly weak despite visible atrophy. Onset is described as relatively insidious compared to other inflammatory myopathies.
No drug treatment is mentioned in any of these abstracts. What remains missing for this Finnish family phenotype is identification of the genetic locus, which was still being sought in 2003, and any subsequent molecular characterisation or replication in other families. For the broader group of distal myopathies, no therapy has been tested in a controlled trial, and patient stratification by specific genetic diagnosis remains incomplete.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2003 · 31 citations
A distinct phenotype of distal myopathy in a large Finnish family
AbstractOBJECTIVES: The authors carried out clinical, histopathologic, immunocytochemical, electrophysiologic, and imaging investigations and molecular genetic analysis in seven patients with distal myopathy belonging to a Finnish family. RESULTS: The disease showed autosomal dominant inheritance. Age at onset ranged from 32 to 45 years. The first symptoms for referral were clumsiness with the hands and frequent stumbling from a steppage gait. Muscle weakness was characterized by early involvement of the small muscles of the hands, gluteus medium, and both anterior and posterior muscle compartments of the legs. The disease progressed to involve other intrinsic muscles of the hands, as well as the forearm muscles, triceps and infraspinatus, and proximal lower limbs. Asymmetry of muscle involvement was common. EMG showed myopathic features, serum CK was normal or slightly elevated, and muscle biopsy showed many rimmed vacuoles and dystrophic changes. There was no evidence of linkage to Welander distal myopathy or tibial muscular dystrophy loci. CONCLUSION: These patients may have a distinct distal myopathy. Genome-wide scan is undertaken in order to identify the disease locus.
Current Opinion in Neurology · 2005 · 27 citations
Distal myopathies
AbstractPURPOSE OF REVIEW: The distal myopathies are a heterogeneous group of disorders that pose a challenge to both the clinician and geneticist. This article summarizes the findings of recent clinical, genetic and molecular studies and the current diagnostic approach to this group of patients. RECENT FINDINGS: Publications over the past 5 years describe a number of new clinical phenotypes and genetic loci and further emphasize the overlap in clinical phenotype between a number of these disorders and between the distal and limb girdle myopathies and hereditary inclusion body myopathies. Recent studies have led to the identification of the genes and mutations responsible for early onset (Laing) myopathy and tibial (Udd) myopathy, and for distal myopathy with rimmed vacuoles (Nonaka), which has been shown to be allelic with quadriceps sparing hereditary inclusion body myopathy (IBM2), and have elucidated the underlying pathogenetic mechanisms in these conditions. New diagnostic approaches using magnetic resonance imaging, and a blood-based assay for dysferlin deficiency, have also been reported. SUMMARY: These findings have important implications for future genetic linkage and gene expression studies and for the diagnostic approach to patients with a distal myopathy phenotype. They also hold promise for the eventual development of therapies for this group of disorders.
Oxford University Press eBooks · 2018 · 0 citations
A Perplexing Pattern of Weakness
AbstractInclusion body myositis (IBM), generally considered one of the immune-mediated inflammatory myopathies, should be readily recognizable by its characteristic clinical features. The disorder typically affects middle-aged to older individuals and has a mean age of onset in the early 60s. Onset before the age of 40 is rare. The disease is characteristically asymmetrical and most often has the relatively unique pattern of involvement of the finger flexors (typically with relative sparing of the metacarpophalangeal flexors compared to the more distal finger flexors) and the quadriceps muscles. In the latter, disproportionate wasting of the vastus medialis and lateralis often occur, with relative sparing of the rectus femoris, so that knee extension is often only mildly weak compared to the observed atrophy. Another striking historical feature is the relatively insidious onset of symptoms in comparison to other inflammatory myopathies.
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.
