DeCure for Neuronopathy, distal hereditary motor, autosomal recessive 10
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for neuronopathy, distal hereditary motor, autosomal recessive 10 — 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 recessive 10 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 recessive 10 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
VRK serine/threonine kinase 1 (VRK1) — VRK1 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 anpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6AC9 · 2.07 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (ANP). Experimental structure, not a prediction.
What the evidence adds up to
The 1980 series of 228 patients with hereditary motor and sensory neuropathy included 120 index cases and 108 affected relatives. Cases were separated into type I (median motor nerve conduction velocity below 38 m/s) and type II (above 38 m/s). Four families with probable autosomal recessive inheritance were identified among type I cases; these displayed significantly slower motor conduction velocity. Two probable autosomal recessive families were detected among type II cases. In the recessive type I cases, there was a greater incidence of weakness, ataxia, tendon areflexia and scoliosis than in the dominant form. The consanguinity rate in the recessive families was high, suggesting these recessive genes are rare. Mean age of onset was significantly earlier for recessive type II cases compared with dominant type II, but did not differ for type I. Motor nerve conduction velocity was significantly slower for recessive type I cases compared with dominant type I, but did not differ for type II.
The 2011 report describes two families with a late-onset autosomal dominant lower motor neuron disease not previously characterised. First symptoms were muscle cramps and fasciculations after age 25–30, followed by slowly progressive proximal and distal weakness without overt atrophy during the first decades of symptoms. Nerve conduction velocities were within normal range. EMG showed widespread neurogenic alterations. Muscle biopsy showed fibre type grouping and group atrophy. MRI showed diffuse fatty-degenerative changes, marked in medial gastrocnemius. Linkage studies excluded known chromosomal loci for hereditary motor neuropathies, suggesting this may be a new disorder.
No abstract in this set addresses autosomal recessive distal hereditary motor neuronopathy type 10 specifically. The 1980 papers describe autosomal recessive forms of hereditary motor and sensory neuropathy (Charcot-Marie-Tooth disease), not pure motor neuronopathy. The 2011 paper describes a dominant, late-onset disorder that is clinically and genetically distinct. No drug treatment, no trial, no survival or response rate data appear in any of these abstracts. What is missing for the specific recessive distal motor neuronopathy is any molecular genetic confirmation of the diagnosis in the reported families, any prospective natural history study, any biomarker, and any clinical trial of any kind.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Brain · 1980 · 831 citations
THE CLINICAL FEATURES OF HEREDITARY MOTOR AND SENSORY NEUROPATHY TYPES I AND II
AbstractObservations have been made on a series of 228 patients with hereditary motor and sensory neuropathy, comprising 120 index cases and 108 affected relatives. These could be separated into genetically distinct type I and type II categories depending upon whether motor nerve conduction velocity in the median nerve was below or above 38 m s-1. These disorders constitute separate genetic subgroups within the clinical spectrum of 'peroneal muscular atrophy'. Type I cases were more numerous. Most were of autosomal dominant inheritance, but a proportion were sporadic. Four families with probable autosomal recessive inheritance were identified; these displayed significantly slower motor conduction velocity. There was a positive correlation between motor conduction velocity in the propositi and that in their relatives in the total type I group which persisted after the autosomal recessive cases had been extracted, indicating further genetic heterogeneity amongst the autosomal dominant families. No X-linked recessive families were encountered. Type I cases had a peak age of onset of symptoms during the first decade of life. In comparison with the type II cases, they displayed a greater tendency to show weakness of the hands, upper limb tremor and ataxia, generalized tendon areflexia and more extensive distal sensory loss, sometimes with acrodystrophic changes. Foot and spinal deformities were more frequent, probably due to the earlier age of onset. Nerve thickening was confined to the type I cases. The onset of symptoms was most often in the second decade in the type II cases, but in some it was delayed, even as late as the seventh decade. Most cases were again of autosomal dominant inheritance, but two probable autosomal recessive families were detected, as well as sporadic cases. Upper limb tremor also occurred in this form but was considerably less common. In both types, males tended to be more severely affected, and asymptomatic affected family members ('formes frustes') were more commonly female.
Journal of Neurology Neurosurgery & Psychiatry · 1980 · 115 citations · open access
Autosomal recessive forms of hereditary motor and sensory neuropathy.
AbstractSix families are described with hereditary motor and sensory neuropathy (HMSN) of probable autosomal recessive inheritance. Four of these were classified as HMSN type I and two as type II. The consanguinity rate in this series was high, suggesting that these recessive genes are rare. In comparison with the dominantly inherited forms of these disorders, the mean age of onset was significantly earlier for the type II cases but did not differ for the type I patients. Motor nerve conduction velocity was significantly less for the type I cases but did not differ for the type II form. The recessive type I cases tended to show a greater incidence of weakness, ataxia, tendon areflexia and scoliosis than in the dominant form. The importance of differentiating such cases from Friedreich's ataxia is emphasised.
AbstractOBJECTIVE: Characterization of a new type of late-onset autosomal dominant lower motor neuron disease. METHODS: Patients from 2 families underwent detailed neurologic, electrophysiologic, muscle biopsy, and laboratory investigations. MRI of lower limbs was performed in selected patients. DNA samples from leukocytes were used for molecular genetic linkage studies. RESULTS: First symptoms were muscle cramps and fasciculations after age 25-30, followed by a slowly progressive proximal and distal weakness without overt atrophy during the first decades of symptoms. Nerve conduction velocities were within normal range and EMG showed widespread neurogenic alterations. Muscle biopsy revealed characteristic neurogenic findings: fiber type grouping and group atrophy. MRI showed diffuse fatty-degenerative changes, marked in medial gastrocnemius. CONCLUSION: Exactly the same clinical phenotype has not previously been described, and linkage studies showed exclusion of known chromosomal loci for hereditary motor neuropathies, suggesting the disease we report may represent a new disorder.
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.
