DeCure for Neuronopathy, distal hereditary motor, autosomal dominant 1
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for neuronopathy, distal hereditary motor, autosomal dominant 1 — 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 moduleNeuronopathy, distal hereditary motor, autosomal dominant 1 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 neuronopathy, distal hereditary motor, autosomal dominant 1 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
immunoglobulin mu DNA binding protein 2 (IGHMBP2) — IGHMBP2 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 4B3F · 2.5 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
The 2011 review of distal hereditary motor neuropathies (dHMN) states that 80% of patients have a mutation in an as-yet undiscovered gene, despite eleven causative genes and four loci having been identified across autosomal dominant, recessive and X-linked patterns. The known genes implicate protein misfolding, RNA metabolism, axonal transport and cation-channel dysfunction, but no drug is mentioned in this review as a treatment for any form of dHMN.
A 1976 study of 14 families with familial motor neuron disease described three autosomal dominant types, distinguished by survival and pathology. The third type had survival beyond 10 years and often beyond 20 years, but no drug intervention was tested or reported. A 1983 Swedish population study of hereditary motor and sensory neuropathies in children found that among 29 cases of the neuronal-axonal type (HMSN II), 26 appeared autosomal dominant; 10% of all children were severely disabled, 70% moderately and 20% mildly. No drug treatment was examined.
A 2009 study mapped an X-linked adult-onset distal hereditary motor neuropathy in one family to the DSMAX locus on chromosome Xq13.1-q21, refining the interval to 1.44 cM. Sequencing excluded mutations in the GJB1 gene and nine positional candidate genes were eliminated as the cause. No drug or therapeutic intervention was tested or proposed in this study.
Across these abstracts, no drug is tested, no treatment is recommended, and no clinical trial of any compound is described for distal hereditary motor neuropathy. What is missing is any clinical trial data, any drug repurposing study, any animal model testing of a candidate molecule, and any patient stratification beyond broad genetic categories. The field lacks a proven pharmacological intervention for any form of dHMN.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
AbstractThe distal hereditary motor neuropathies (dHMN) comprise a heterogeneous group of diseases that share the common feature of a length-dependent predominantly motor neuropathy. Many forms of dHMN have minor sensory abnormalities and/or a significant upper-motor-neuron component, and there is often an overlap with the axonal forms of Charcot-Marie-Tooth disease (CMT2) and with juvenile forms of amyotrophic lateral sclerosis and hereditary spastic paraplegia. Eleven causative genes and four loci have been identified with autosomal dominant, recessive and X-linked patterns of inheritance. Despite advances in the identification of novel gene mutations, 80% of patients with dHMN have a mutation in an as-yet undiscovered gene. The causative genes have implicated proteins with diverse functions such as protein misfolding (HSPB1, HSPB8, BSCL2), RNA metabolism (IGHMBP2, SETX, GARS), axonal transport (HSPB1, DYNC1H1, DCTN1) and cation-channel dysfunction (ATP7A and TRPV4) in motor-nerve disease. This review will summarise the clinical features of the different subtypes of dHMN to help focus genetic testing for the practising clinician. It will also review the neuroscience that underpins our current understanding of how these mutations lead to a motor-specific neuropathy and highlight potential therapeutic strategies. An understanding of the functional consequences of gene mutations will become increasingly important with the advent of next-generation sequencing and the need to determine the pathogenicity of large amounts of individual genetic data.
AbstractBased on a clinical, pathologic, and genetic study of 14 families, at least three types of familial motor neuron disease can be distinguished, all apparently of autosomal dominant transmission. The first is characterized by rapid, progressive loss of motor function with predominantly lower motor neuron manifestations and a course lasting less than 5 years. Pathologic changes are limited to the anterior horn cells and pyramidal tracts. The second type is clinically identical to the first, but at autopsy additional changes are found in the posterior columns, Clarke's column, and spinocerebellar tracts. The third type is characterized by a much longer survival usually beyond 10 and after more than 20 years in affected family members but is otherwise similar to the second type.
Archives of Pediatrics and Adolescent Medicine · 1973 · 30 citations
Hereditary Recurrent Brachial Neuropathy
AbstractA 7-year-old boy with hereditary recurrent brachial neuropathy is described and the disease is traced through three generations. The disease is thought to be transmitted by an autosomal dominant gene. There is a wide spectrum of severity of attacks which have a tendency to recur at long intervals to appear during pregnancy or parturition. A troublesome but generally benign course can be predicted. There is no evidence at this time to believe that treatment other than supportive care has any real value.
HEREDITARY MOTOR AND SENSORY NEUROPATHIES IN SWEDISH CHILDREN I
AbstractThe prevalence of hereditary motor and sensory neuropathies (HMSN) and their distribution according to the severity of the disability were studied in a population-based series of Swedish children 2-15 years old. The prevalence per 100 000 of total peroneal muscle atrophies was 21.6 and of all clinical HMSN 19.0 Among HMSN, de- and remyelinating types (HMSN I) constituted 8 per 100000 and neuronal-axonal types (HMSN II) 11. Eighteen of the 21 HMSN I cases and 26 of the 29 HMSN II were considered to represent an autosomal dominant mode of inheritance. Ten per cent of all children were severely, 70% moderately and 20% mildly disabled. All the severely affected children belonged to the HMSN I group and 9 of the 10 mildly affected to HMSN II.
X-linked distal hereditary motor neuropathy maps to the DSMAX locus on chromosome Xq13.1-q21
AbstractOBJECTIVE: To clinically characterize and map the gene locus in a three-generation family with an X-linked adult-onset distal hereditary motor neuropathy. METHODS: Microsatellite markers spanning the juvenile distal spinal muscular atrophy (DSMAX) locus were genotyped and analyzed using genetic linkage analysis. The promoter, untranslated and coding region of the gap junction beta1 (GJB1) gene was sequenced. Nine positional candidate genes were screened for disease mutations using high-resolution melt (HRM) analysis. RESULTS: The family showed significant linkage to markers on chromosome Xq13.1-q21. Haplotype construction revealed a disease-associated haplotype between the markers DXS991 and DX5990. Sequence analysis excluded pathogenic changes in the coding and promoter regions of the GJB1 gene. Additional fine mapping in the family refined the DSMAX locus to a 1.44-cM interval between DXS8046 and DXS8114. HRM analysis did not identify disease-associated mutations in the coding region of nine candidate genes. CONCLUSION: We have identified a family with adult-onset distal hereditary motor neuropathy that refines the locus reported for juvenile distal spinal muscular atrophy (DSMAX) on chromosome Xq13.1-q21. Exclusion of mutations in the coding and regulatory region of the GJB1 gene eliminated the CMTX1 locus as a cause of disease in this family. Nine positional candidate genes in the refined interval underwent mutation analysis and were eliminated as the pathogenic cause of DSMAX in this family. The syndrome in this family may be allelic to the juvenile distal spinal muscular atrophy first reported at this locus.
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.
