DeCure for Neuronopathy, distal hereditary motor, autosomal recessive 9
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for neuronopathy, distal hereditary motor, autosomal recessive 9 — 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 9 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 9 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
coenzyme Q7, hydroxylase (COQ7) — COQ7 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 1sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7SSS · 2.4 Å · ligand (1S)-2-{[(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL STEARATE (PEV). Experimental structure, not a prediction.
What the evidence adds up to
Six families with autosomal recessive hereditary motor and sensory neuropathy were described in 1980, four classified as type I and two as type II. Consanguinity was high, suggesting the recessive genes are rare. Mean age of onset was significantly earlier for recessive type II cases compared to dominant forms, but did not differ for type I. Motor nerve conduction velocity was significantly less for recessive type I cases but did not differ for type II. Recessive type I cases tended to show greater incidence of weakness, ataxia, tendon areflexia and scoliosis than the dominant form.
A 2023 review notes that around 30 causative genes have been identified for distal hereditary motor neuropathies, with inheritance patterns that can be autosomal dominant, recessive, or X-linked. Only about 30% of dHMN patients receive a genetic diagnosis despite advances in molecular genetics. The term "motor neuronopathies" now encompasses dHMN, Charcot Marie Tooth type 2 overlap groups with minor sensory involvement, spinal muscular atrophy with lower extremity predominance, arthrogryposis multiplex congenita, juvenile ALS, and motor neuropathies with central nervous system involvement, covering 55 causative genes.
A 2000 autopsy case of a girl with non-consanguineous parents described a presumably autosomal recessive HMSN associated with deafness, mental retardation, and epilepsy. Autopsy showed complete absence of large myelinated fibers in peripheral motor and sensory nerves, corresponding to a lack of large neurons in dorsal root ganglia and anterior horns, moderate neurogenic muscle atrophy, and nearly complete absence of neurons in the dentate nucleus. Molecular genetic analyses found no alterations in the survival motor neuron gene or the PMP-22 gene.
A 2008 report on hereditary neuralgic amyotrophy, an autosomal dominant disorder associated with SEPT9 mutation on chromosome 17q25, described three family members with the C262T SEPT9 mutation. The degree of motor weakness and recovery was variable within the family, and severity and recovery may have been a function of comorbid medical conditions. What remains missing for autosomal recessive distal hereditary motor neuronopathy is a clear genetic diagnosis for most patients, systematic clinical trials given the rarity of each genetic subtype, and patient stratification that could distinguish these cases from overlapping disorders such as Friedreich's ataxia or juvenile ALS.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
Journal of Clinical Neuromuscular Disease · 2008 · 14 citations
Painful Brachial Plexopathies in SEPT9 Mutations: Adverse Outcome Related to Comorbid States
AbstractHereditary neuralgic amyotrophy (HNA), an autosomal dominant disorder associated with SEPT9 mutation located on chromosome 17q25, causes recurrent painful weakness with sensory disturbances in a brachial distribution. We present electrophysiological, clinical phenotype, and molecular genetic data of three members from a family with HNA with the C262T SEPT9 mutation. The degree of motor weakness and recovery is variable within this family. Severity and recovery from motor deficits may have been a function of comorbid medical conditions. To our knowledge, this is the first report to confirm SEPT9 mutation in a family with suspected HNA.
Journal of the Peripheral Nervous System · 2000 · 9 citations
Hereditary motor and sensory neuropathy with absence of large myelinated fibers due to absence of large neurons in dorsal root ganglia and anterior horns, clinically associated with deafness, mental retardation, and epilepsy (HMSN‐ADM)
AbstractHereditary motor and sensory neuropathy (HMSN) with autosomal recessive inheritance represents a genetically heterogeneous group of disorders with variable clinical, pathologic and electrophysiologic manifestations. A new variant of autosomal recessive HMSN, clinically defined by sensorimotor polyneuropathy associated with deafness and mental retardation, has recently been described. We report on the first autopsy case with this type of HMSN: a girl of non-consanguineous parents with a presumably autosomal recessive type of motor and sensory neuropathy clinically associated with deafness, mental retardation, and epilepsy. The autopsy showed complete absence of large myelinated fibers in peripheral motor and sensory nerves corresponding to a lack of large neurons in dorsal root ganglia and anterior horns of the spinal cord, moderate neurogenic muscle atrophy, and nearly complete absence of neurons in the dentate nucleus of the cerebellum. Molecular genetic analyses in our case revealed neither genetic alterations in the survival motor neuron gene nor in the PMP-22 gene.
Annals of the New York Academy of Sciences · 1999 · 4 citations
Distal Hereditary Motor Neuronopathy of the Jerash Type
AbstractABSTRACT: A novel form of autosomal recessive distal hereditary motor neuronopathy (distal HMN) is reported. The presence of pyramidal signs within the early stages of the disease with persistence of knee hyperreflexia form distinctive clinical features. We have mapped the HMN‐J gene to chromosome 9p21.1‐p12, within an estimated interval of 1.2‐Mb.
Brain Communications · 2023 · 1 citations · open access
Novel and nano-rare genetic causes of paediatric-onset motor neuronopathies
AbstractWe read the article by Zambon et al. 1 regarding paediatric-onset motor neuropathies with great interest.The authors described clinical details and novel genetic findings with associated molecular mechanisms in this rapidly evolving field.Around 30 causative genes have been identified to give rise to distal hereditary motor neuropathies (dHMN).The inheritance pattern can be autosomal dominant, recessive, or X-linked, increasing these disorders' genetic complexity.Only about 30% dHMN patients receive a genetic diagnosis despite the advances in molecular genetics.The phenotypical presentation of pure dHMN classified by Harding et al. is relatively uniform 2 .On the other hand, significant overlap between Charcot Marie Tooth type 2 (CMT2), complicated hereditary spastic paraplegia (HSP), juvenile forms of amyotrophic lateral sclerosis (jALS), and distal myopathies can cause terminological confusion.In this regard, Zambon and colleagues used "motor neuronopathies" term, which encompasses dHMN, CMT2 overlap group with minor sensory involvement as well as spinal muscular atrophy with lower extremities predominance, arthrogryposis multiplex congenita, jALS, and motor neuropathies with central nervous system involvement.These broad spectra of clinical phenotypes cover 55 causative genes,
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.
