DeCure for Neuronopathy, distal hereditary motor, type 2B
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for neuronopathy, distal hereditary motor, type 2B — screening already-approved drugs against its 2-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, type 2B maps to a 2-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, type 2b 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
fukutin related protein (FKRP) — FKRP 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 cdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6KAJ · 2.2249 Å · ligand CYTIDINE-5'-DIPHOSPHATE (CDP). Experimental structure, not a prediction.
What the evidence adds up to
A Chinese family with nine patients across four generations carried a heterozygous 263A→G mutation in BSCL2, producing an N88S substitution. Onset ranged from 13 to 40 years. Six had distal hereditary motor neuropathy type II with predominant lower extremity weakness; one of those also had pyramidal signs. Three women had distal hereditary motor neuropathy type V with predominant hand atrophy. Electrophysiology in one patient showed reduced compound muscle action potential amplitude. Sural nerve biopsy showed loss of large myelinated fibres and fibre regeneration. Sensory nerve axonal degeneration was also present. Different distal motor neuropathy phenotypes occurred within the same family carrying the same N88S mutation.
Two siblings with autosomal recessive spastic paraparesis and severe distal limb muscle amyotrophy showed slight to moderate motor conduction slowing, moderate to severe reduction of motor action potentials, denervation potentials, and increased distal motor latencies. The authors note this syndrome had not been reported since 1904 and 1905, and constitutes another rare, benign, complicated form of hereditary spastic paraparesis.
A 2023 commentary on paediatric-onset motor neuronopathies states that around 30 causative genes have been identified for distal hereditary motor neuropathies (dHMN). Inheritance can be autosomal dominant, recessive, or X-linked. Despite advances, only about 30% of dHMN patients receive a genetic diagnosis. The term "motor neuronopathies" now encompasses dHMN, Charcot-Marie-Tooth type 2 overlap 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.
What is still missing is a genetic diagnosis for the majority of dHMN patients, systematic correlation between specific mutations and the variable phenotypes seen even within single families, and prospective studies that stratify patients by age of onset, pattern of weakness, and sensory involvement to clarify whether these represent distinct entities or a continuum.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neuropathology · 2009 · 14 citations
Clincial and pathological study of distal motor neuropathy with N88S mutation in BSCL2
AbstractSeipinopathy is an autosomal dominant inherited distal motor neuropathy caused by Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene mutations. We describe a Chinese family with seipinopathy in which nine patients from four successive generations were involved. The onset of age was from 13 to 40 years. Among them six were distal hereditary motor neuropathy type II with predominant weakness of lower extremities, while one of them was accompanied by pyramidal signs. The other three women were distal hereditary motor neuropathy type V with predominant atrophy of hands. Electrophysiological results in one patient demonstrated reduction of amplitude of compound muscle action potentials. Sural nerve biopsy showed loss of large myelinated fibers and fiber regeneration. Gene analysis revealed a heterozygous 263A-->G mutation in BSCL2 gene resulting in amino acid substitutions in N88S. This report suggests that a different type of distal hereditary motor neuropathy could exist within one family carrying N88S mutations. The axonal degeneration of sensory nerves appeared also in the disease.
Autosomal recessive paraparesis with amyotrophy of the hands and feet
AbstractWe present 2 sibs with autosomal recessive spastic paraparesis and severe amyotrophy of the distal limb muscles. Elaborate neurophysiologic studies disclosed slight to moderate slowing of motor conduction, moderate to severe reduction of motor action potentials, denervation potentials, and increased distal motor latencies. This syndrome, not having been reported since the papers by Ormerod (5) in 1904 and Holmes (6) in 1905, constitutes another rare, benign, complicated form of hereditary spastic paraparesis.
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.
