DeCure for Spastic paraplegia, optic atropy, and neuropathy
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for spastic paraplegia, optic atropy, and neuropathy — 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 moduleSpastic paraplegia, optic atropy, and neuropathy 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 spastic paraplegia, optic atropy, and neuropathy 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
kinesin light chain 2 (KLC2) — KLC2 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 unxdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3EDT · 2.7 Å · ligand UNKNOWN ATOM OR ION (UNX). Experimental structure, not a prediction.
What the evidence adds up to
A 2003 study of 12 families with autosomal dominant hereditary spastic paraplegia found no clinical differences between patients with or without mutations in the spastin gene (SPG4). Motor evoked potentials and nerve conduction studies were almost normal in those with SPG4, whereas non-SPG4 families had prolonged central motor conduction times or marked peripheral neuropathy, or both.
A 2022 case report described a 15-year-old male with a novel heterozygous SPG7 variant, c.1224T>G:p.(Asp408Glu), who presented with early onset isolated optic atrophy and infantile nystagmus before any neurological symptoms appeared. The authors concluded that SPG7 should be considered a cause of infantile nystagmus with optic atrophy.
A 2023 case series of five patients aged 8 to 48 years with pathogenic SPG7 mutations and optic atrophy found that all had progressive vision loss, typically bilateral. Several had previous diagnoses of peripheral neuropathy, including Guillain-Barré Syndrome. Three patients carried the Ala510Val variant. Four of the five had a prior diagnosis of peripheral neuropathy. The authors noted that a single pathogenic SPG7 variant may be associated with both peripheral neuropathy and optic neuropathy, and recommended SPG7 testing in patients with unexplained symmetric papillomacular bundle damage.
What is still missing is prospective data on the natural history of SPG7-associated optic neuropathy, standardised outcome measures for vision loss in this population, and any trial of a treatment. No drug was mentioned in any of the 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 · 2003 · 35 citations
Neurophysiological findings in <i>SPG4</i> patients differ from other types of spastic paraplegia
AbstractThe authors examined 12 families with autosomal dominant hereditary spastic paraplegia for phenotypic characteristics predicting the underlying genotype. They found no clinical differences between patients with or without mutations in the spastin gene (SPG4). Motor evoked potentials and nerve conduction studies were almost normal in those with SPG4. In contrast, non-SPG4 families had prolonged central motor conduction times or marked peripheral neuropathy, or both.
American Journal of Medical Genetics Part A · 2022 · 5 citations · open access
Expanding <i>SPG7</i> dominant optic atrophy phenotype: Infantile nystagmus and optic atrophy without spastic paraplegia
AbstractSpastic paraplegia is a neurodegenerative disorder characterized by progressive leg weakness and spasticity due to degeneration of corticospinal axons. SPG7 encodes paraplegin, and pathogenic variants in the gene cause hereditary spastic paraplegia as an autosomal recessive trait. Various ophthalmological findings including optic atrophy, ophthalmoplegia, or nystagmus have been reported in patients with spastic paraplegia type 7. We report a 15-year-old male patient with a novel heterozygous variant, c.1224T>G:p.(Asp408Glu) in SPG7 (NM_003119.3) causing early onset isolated optic atrophy and infantile nystagmus prior to the onset of neurological symptoms. Therefore, SPG7 should be considered a cause of infantile nystagmus with optic atrophy.
Journal of Neuro-Ophthalmology · 2023 · 1 citations
Spastic Paraplegia Type 7-Associated Optic Neuropathy: A Case Series
AbstractBACKGROUND: Hereditary optic neuropathies comprise a group of clinically and genetically heterogeneous disorders. Optic neuropathy has been previously reported in families with spastic paraplegia type 7 ( SPG7) gene mutations. However, the typical time course and clinical presentation of SPG7 -associated optic neuropathy is poorly understood. We report a series of 5 patients harboring pathogenic SPG7 mutations who originally presented to a neuro-ophthalmology clinic with symptoms of optic neuropathy. METHODS: Retrospective case series of 5 patients with pathogenic SPG7 mutations and optic atrophy from 3 neuro-ophthalmology clinics. Demographic, clinical, diagnostic, and treatment data were collected and reported by the clinician authors. RESULTS: Five patients ranging in age from 8 to 48 years were evaluated in the neuro-ophthalmology clinic. Although there were variable clinical presentations for each subject, all noted progressive vision loss, typically bilateral, and several also had previous diagnoses of peripheral neuropathy (e.g., Guillain-Barré Syndrome). Patients underwent neuro-ophthalmic examinations and testing with visual fields and optic coherence tomography of the retinal nerve fiber layer. Genetic testing revealed pathogenic variants in the SPG7 gene. CONCLUSIONS: Five patients presented to the neuro-ophthalmology clinic with progressive vision loss and were diagnosed with optic atrophy. Although each patient harbored an SPG7 mutation, this cohort was phenotypically and genotypically heterogeneous. Three patients carried the Ala510Val variant. The patients demonstrated varying degrees of visual acuity and visual field loss, although evaluations were completed during different stages of disease progression. Four patients had a previous diagnosis of peripheral neuropathy. This raises the prospect that a single pathogenic variant of SPG7 may be associated with peripheral neuropathy in addition to optic neuropathy. These results support the consideration of SPG7 testing in patients with high suspicion for genetic optic neuropathy, as manifested by symmetric papillomacular bundle damage without clear etiology on initial workup. Applied judiciously, genetic testing, including for SPG7 , may help clarify the cause of unexplained progressive optic neuropathies.
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.
