DeCure for Neuronopathy, distal hereditary motor, autosomal dominant 10
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for neuronopathy, distal hereditary motor, autosomal dominant 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 dominant 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 dominant 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.
What the evidence adds up to
The 228 patients in the 1980 series were separated into type I (motor nerve conduction velocity below 38 m/s) and type II (above 38 m/s). Type I cases were more numerous, most with autosomal dominant inheritance, and had a peak age of onset in the first decade. They showed a greater tendency to hand weakness, upper limb tremor, ataxia, generalised tendon areflexia, and more extensive distal sensory loss. Nerve thickening was confined to type I. Type II cases most often had onset in the second decade, but some were delayed as late as the seventh decade. Upper limb tremor was considerably less common in type II. In both types, males tended to be more severely affected, and asymptomatic affected family members were more commonly female.
Among six families with probable autosomal recessive inheritance, the consanguinity rate was high. Mean age of onset was significantly earlier for recessive type II cases compared with the dominant form, but did not differ for type I. Motor nerve conduction velocity was significantly slower for recessive type I cases, but did not differ for type II. Recessive type I cases tended to show a greater incidence of weakness, ataxia, tendon areflexia, and scoliosis than in the dominant form.
A novel autosomal recessive distal hereditary motor neuronopathy was reported in 7 consanguineous families from Jordan, with onset between 6 and 10 years of age. Symptoms began with weakness and atrophy of the lower limbs associated with pyramidal features, and progressed to the upper limbs within 2 years. Neurophysiological studies showed normal conduction velocities, reduced compound motor action potential amplitudes, normal sensory nerve action potentials, and chronic neurogenic changes. The gene was mapped to a 0.54-cM region on chromosome 9p21.1-p12, with a maximum LOD score of 19.80.
The neuronal forms of hereditary motor and sensory neuropathy are genetically heterogeneous, with autosomal dominant, autosomal recessive, and X-linked dominant inheritance. All three forms are characterised by degeneration of select motor and sensory neurons with distal-to-proximal fibre loss. Motor and sensory nerve conduction velocities are only moderately slowed, and evoked amplitudes are reduced according to fibre loss. The gene locus remains unknown for both autosomal dominant and autosomal recessive types. In a population-based study of Swedish children, the prevalence of all clinical HMSN was 19.0 per 100,000. Ten per cent of all children were severely disabled, 70% moderately, and 20% mildly. All severely affected children belonged to HMSN I, and 9 of the 10 mildly affected belonged to HMSN II. What is still missing is a clear molecular diagnosis for most autosomal dominant and recessive forms, any proven disease-modifying treatment, and the patient stratification needed to distinguish the many genetic subtypes that share the same clinical picture.
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.
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.
A novel form of distal hereditary motor neuronopathy maps to chromosome 9p21.1–p12
AbstractDistal hereditary motor neuronopathies (dHMNs) form a heterogeneous group of rare disorders characterized by distal weakness and wasting in the limbs with no significant sensory involvement. Harding has classified dHMNs into seven categories based on clinical and genetic criteria. We report a novel form of autosomal recessive dHMN in 7 consanguineous families located in the Jerash region of Jordan. Onset of the disease is between 6 and 10 years of age and is characterized by weakness and atrophy of the lower limbs associated with pyramidal features. Within 2 years, symptoms progress to the upper limbs. Neurophysiological studies typically show normal conduction velocities, reduced compound motor action potential amplitudes, normal sensory nerve action potentials, and chronic neurogenic changes on needle electromyography. No significant abnormalities are seen on sural nerve biopsy. We call this novel form of dHMN Jerash hereditary motor neuronopathy. We studied the families at the molecular genetic level and mapped the Jerash hereditary motor neuronopathy gene to an approximately 0.54-cM region on chromosome 9p21.1-p12, flanked by microsatellite polymorphic marker loci D9S1845 and D9S1791. A maximum LOD score of 19.80 at theta = 0.001 was obtained between the disease and locus D9S1878.
Brain Pathology · 1993 · 32 citations · open access
Hereditary Motor and Sensory Neuropathy: HMSN Type II (Neuronal Type) and X‐linked HMSN
AbstractThe neuronal forms of hereditary motor and sensory neuropathy (HMSN) are genetically heterogeneous with observed autosomal dominant, autosomal recessive and X-linked dominant inheritance. All three forms are characterized by degeneration of select populations of motor and sensory neurons with accompanying atrophy and degeneration of their axons. Large calibre myelinated fibres are predominantly affected and fibre degeneration and fibre loss progresses from distally to proximally. Attempts of regeneration are noted in all except the severe childhood form. The clinical picture is that of peroneal and distal leg muscle wasting and weakness, distal sensory loss and areflexia. Hand muscles may be severely affected in the autosomal recessive and X-linked dominant forms. Motor and sensory nerve conduction velocities are only moderately slowed and evoked maximum compound motor and sensory amplitudes are reduced according to the degree of fibre loss. The gene locus remains unknown in both the autosomal dominant and autosomal recessive types. For the X-linked dominant HMSN, the gene locus has been mapped closely by linkage analysis to DNA loci in the pericentromeric region of the X-chromosome.
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.
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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