DeCure for Neuronopathy, distal hereditary motor, autosomal recessive 7
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for neuronopathy, distal hereditary motor, autosomal recessive 7 — 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 7 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 7 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
In a 1980 series of 228 patients with hereditary motor and sensory neuropathy, cases were separated into type I and type II based on median nerve motor conduction velocity above or below 38 m/s. Type I cases were more numerous, mostly autosomal dominant, but four families with probable autosomal recessive inheritance were identified and displayed significantly slower motor conduction velocity. Type I patients had a peak age of onset in the first decade and showed greater tendency toward hand weakness, upper limb tremor, ataxia, generalised tendon areflexia, and more extensive distal sensory loss. Two probable autosomal recessive families were also detected among type II cases, whose onset was most often in the second decade but could be delayed into the seventh decade.
A 2011 report described 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, and muscle biopsy revealed fiber type grouping and group atrophy. Linkage studies excluded known chromosomal loci for hereditary motor neuropathies, suggesting this may represent a new disorder.
A 2016 report described a mother and daughter with distal hereditary motor neuropathy type 7, in whom the diagnosis became apparent through initial difficulty in singing due to early vocal cord dysfunction. This rare neuropathy had been identified in two apparently unrelated families in Wales. The family had the common truncating mutation in the SLC5A7 gene. The authors note that advances in genetic analysis broaden understanding of potential molecular mechanisms and may allow more directed therapy, but no such therapy is reported.
What is still missing for these rare neuronopathies is systematic collection of natural history data across genetically defined subtypes, funding for trials large enough to detect benefit in ultrarare populations, and validated outcome measures that capture the slow progression and vocal cord involvement. No drug treatment is tested or recommended in any of these abstracts.
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.
Hereditary motor and sensory neuropathy‐russe: New autosomal recessive neuropathy in balkan gypsies
AbstractA novel peripheral neuropathy of autosomal recessive inheritance has been identified in Balkan Gypsies and termed hereditary motor and sensory neuropathy-Russe (HMSN-R). We investigated 21 affected individuals from 10 families. Distal lower limb weakness began between the ages of 8 and 16 years, upper limb involvement beginning between 10 and 43 years, with an average of 22 years. This progressive disorder led to severe weakness of the lower limbs, generalized in the oldest subject (aged 57 years), and marked distal upper limb weakness. Prominent distal sensory loss involved all modalities, resulting in neuropathic joint degeneration in two instances. All patients showed foot deformity, and most showed hand deformity. Motor nerve conduction velocity was moderately reduced in the upper limbs but unobtainable in the legs. Sensory nerve action potentials were absent. There was loss of larger myelinated nerve fibers and profuse regenerative activity in the sural nerve. HMSN-R is a new form of autosomal recessive inherited HMSN caused by a single founder mutation in a 1 Mb interval on chromosome 10q.
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.
Practical Neurology · 2016 · 10 citations · open access
Distal hereditary motor neuropathy with vocal cord paresis: from difficulty in choral singing to a molecular genetic diagnosis
AbstractPatients presenting with distal weakness can be a diagnostic challenge; the eventual diagnosis often depends upon accurate clinical phenotyping. We present a mother and daughter with a rare form of distal hereditary motor neuropathy type 7 in whom the diagnosis became apparent by initial difficulty in singing, from early vocal cord dysfunction. This rare neuropathy has now been identified in two apparently unrelated families in Wales. This family's clinical presentation is typical of distal hereditary motor neuropathy type 7, and they have the common truncating mutation in the SLC5A7 gene. Advances in genetic analysis of these rare conditions broaden our understanding of their potential molecular mechanisms and may allow more directed therapy.
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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