DeCure for Neuronopathy, distal hereditary motor, autosomal dominant 11
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for neuronopathy, distal hereditary motor, autosomal dominant 11 — 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 11 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 11 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
spectrin alpha, non-erythrocytic 1 (SPTAN1) — SPTAN1 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 3FB2 · 2.3 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Based 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. One type is characterised by rapid, progressive loss of motor function with predominantly lower motor neuron manifestations and a course lasting less than 5 years. Another type is clinically identical but shows additional pathologic changes in the posterior columns, Clarke's column, and spinocerebellar tracts. A third type is characterised by 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 2011 report described a new type of late-onset autosomal dominant lower motor neuron disease in patients from two families. 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. Nerve conduction velocities were within normal range. Linkage studies showed exclusion of known chromosomal loci for hereditary motor neuropathies, suggesting the disease may represent a new disorder. The association between hereditary motor and sensory neuropathy and optic atrophy has been termed HMSN type VI, with autosomal dominant inheritance reported in three generations affected with optic atrophy and an asymptomatic, mainly sensory, neuropathy.
The demyelinating hereditary motor and sensory neuropathies are a group of inherited progressive neuropathies with markedly decreased nerve conduction velocity and chronic segmental demyelination. Autosomal dominant demyelinating HMSN is genetically heterogeneous, with loci on chromosome 17 (HMSN Ia), chromosome 1 (HMSN Ib), and a locus not linked to either. HMSN type Ia is the most common form, resulting from a duplication of chromosome 17p11.2 or a point mutation in the PMP-22 gene. Autosomal recessive demyelinating HMSN shows a broad spectrum of pathological features, with four discernible subtypes based on morphological characteristics; the genetic defect or defects are not yet known.
In six Russian patients aged 14-40 years with suspicion of HMSN, neurophysiological examination revealed motor and sensory neuropathy with neuromyotonia signs in all cases. All six patients had a homozygous variant of recessive mutations c.110G/C (p.Arg37Pro) in the HINT1 gene. What remains missing for this group of disorders is a unified classification that accounts for the wide clinical and genetic heterogeneity, as well as systematic genetic testing in larger populations to clarify the prevalence of specific mutations like HINT1 across different ethnic groups. No trial designs or patient stratification strategies for any drug therapy are reported in 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.
Neurology · 1976 · 98 citations
Familial motor neuron disease
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.
Brain Pathology · 1993 · 59 citations · open access
Hereditary Demyelinating Motor and Sensory Neuropathy
AbstractThe demyelinating hereditary motor and sensory neuropathies (HMSN) are a group of inherited progressive neuropathies with markedly decreased nerve conduction velocity and chronic segmental demyelination in the peripheral nerve. Inheritance is autosomal dominant (AD) or autosomal recessive (AR). Autosomal dominant demyelinating HMSN (AD HMSN type I) is genetically heterogeneous and at least three different gene loci have been identified: a locus on chromosome 17 (HMSN Ia), a locus on chromosome 1 (HMSN Ib) and a locus not linked to chromosome 17 or 1 (HMSN nonIa-nonIb). HMSN type Ia is the most common form of AD HMSN. Recently, it has been demonstrated that the HMSN Ia phenotype results either from a duplication of chromosome 17p11.2 or from a point mutation in the peripheral nerve-specific PMP-22 gene which is located in the duplication. Pathology of type Ia is dominated by chronic segmental demyelination with classical onion bulbs. Autosomal recessive demyelinating HMSN shows a broad spectrum of pathological features. The genetic defect or defects are not yet known. On the basis of morphological characteristics we were able to discern four subtypes. Two AR subtypes are clinically and electrophysiologically comparable to AD HMSN type I, namely AR HMSN type I with basal lamina onion bulbs and AR HMSN type I with focally folded myelin. Two AR subtypes with amyelination, respectively or hypomyelination of the peripheral nerves are also more severely affected both clinically and electrophysiologically and could be designated as HMSN type III. A third condition with a HMSN type III phenotype shows mainly classical onion bulbs in peripheral nerves, but the inherited nature of this disorder is uncertain and identical features have been described in steroid-responsive inflammatory demyelinating neuropathy. The morphologically based subtypes of AR demyelinating HMSN may represent different genetic disorders, allelic differences or phenotypic variations.
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.
Journal of Neurology Neurosurgery & Psychiatry · 1996 · 19 citations · open access
Autosomal dominant optic atrophy with asymptomatic peripheral neuropathy.
AbstractThe association between hereditary motor and sensory neuropathy (HMSN) and optic atrophy has been termed HMSN type VI. The autosomal dominant inheritance of this syndrome is reported. Three generations were affected with optic atrophy, which differed in some respects from classic dominant optic atrophy, and an asymptomatic, mainly sensory, neuropathy.
Neuromuscular Diseases · 2017 · 5 citations · open access
Clinical and genetic characteristics of autosomal recessive axonal neuropathy with neuromyotonia in Russian patients
AbstractIntroduction. Hereditary motor and sensory neuropathies are genetically heterogeneous group of disorders characterized by a progressive muscle weakness, atrophy of hand and leg muscles often associated with deformations, and mild to moderate sensory loss. Axonal neuropathy with neuromyotonia (AR-ANM) is one of the rarest autosomal recessive hereditary neuropathies. Materials and methods. Six (6) patients (4 men, 2 women) aged 14–40 years from unrelated families with suspicion of HMSN were examined clinically, neurophysiologically and using DNA analysis. Results. Neurophysiological examination revealed motor and sensory neuropathy with neuromyotonia signs in all patients. In all cases homozygous variant of recessive mutations с.110G/C (р.Arg37Pro) in the gene encoding the histidine triad nucleotide binding protein 1 (HINT1) has been revealed. Conclusion. There is the first description of the clinical and neurophysiological features of six patients with AR-ANM in Russia.
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.
