DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hereditary spastic paraplegia 5A — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHereditary spastic paraplegia 5A maps to a 5-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 hereditary spastic paraplegia 5a 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
mucolipin TRP cation channel 1 (MCOLN1) — MCOLN1 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 1s,2sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7MGL · 2.9 Å · ligand N-{(1S,2S)-2-[4-(2-methoxyphenyl)piperazin-1-yl]cyclohexyl}benzenesulfonamide (ZB4). Experimental structure, not a prediction.
What the evidence adds up to
A large consanguineous Omani family with an autosomal recessive form of hereditary spastic paraplegia was studied. Age at onset ranged from 6 to 11 years, the disease was progressive, and intellectual disability was present, with seizures in two individuals. A shared 20.4 Mb region of homozygosity on chromosome 16q21-q23.1 was found in all affected individuals, with a peak multipoint lod score of 4.86. This defined a novel locus, SPG35. Sequencing of two candidate genes in that region, DYNC1LI2 and VPS4A, identified no disease-causing mutations.
In Caucasian populations, heterozygous Spastin mutations account for the majority of HSP patients, with predominant clinical manifestation in the third or fourth decade. Childhood onset is more common in less frequent forms such as SPG3a or complicated HSP, for example SPG11. Hereditary spastic paraplegia with thin corpus callosum is a recognised childhood-onset form.
No drug, treatment, or intervention of any kind is mentioned in any of these abstracts. No clinical trial data, no survival figures, no response rates, and no molecular target for therapy are reported. The genetic locus for SPG35 was mapped, but the causative gene was not identified in this family. What is still missing is identification of the SPG35 gene, any understanding of the underlying molecular mechanism, any animal or cellular model, any drug screening effort, and any patient stratification beyond this single Omani family.
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 · 2008 · 57 citations
A novel locus for an autosomal recessive hereditary spastic paraplegia (SPG35) maps to 16q21-q23
AbstractBACKGROUND: The hereditary spastic paraplegias (HSPs) are a group of clinically and genetically heterogeneous neurodegenerative disorders in which the cardinal pathologic feature is upper motor neuron degeneration leading to progressive spasticity and weakness of the lower limbs. To date, 14 autosomal recessive HSP loci have been mapped. METHODS: We have identified a large consanguineous Omani family in which an autosomal recessive form of HSP is segregating. The age at onset varied from 6 to 11 years and the course of the disease is progressive with intellectual disability and is associated with seizures in two individuals. To map the chromosomal location of the causative gene we undertook 250K gene chip SNP analyses of all affected individuals assuming that a founder mutation was responsible. RESULTS: All affected individuals shared a 20.4 Mb (3.25 cM) region of homozygosity located on chromosome 16q21-q23.1, defined by SNP markers rs149428 and rs9929635 (peak multipoint lod score of 4.86). Two candidate genes, dynein, cytoplasmic 1, light intermediate chain 2 (DYNC1LI2) and vacuolar protein sorting 4 homolog A (VPS4A), were sequenced but no disease causing mutations were identified. CONCLUSION: We have mapped the chromosomal location of a novel gene responsible for a form of hereditary spastic paraplegia (HSP) (SPG35) and defined its clinical presentation.
Mutation Spectrum and Infantile Manifestation in Hereditary Spastic Paraplegia
AbstractAims: Hereditary spastic paraplegia (HSP) is genetically heterogeneous and clinically characterized by gait impairment because of weakness and spasticity of the lower limbs. In Caucasian populations, heterozygous Spastin mutations account for the majority of patients (SPG4) with predominant clinical manifestation within the third or fourth decade of life. A clinical manifestation during childhood is well known, but more common in less frequent forms such as SPG3a or complicated HSP, for example, SPG11.
Hereditary spastic paraplegia with thin corpus callosum – childhood onset in two patients
AbstractBackground: The hereditary spastic paraplegias (HSPs) are a group of rare disorders with the predominant clinical feature of spastic gait. They are subdivided into pure and complicated forms according to whether the disorder is associated with other neurologic abnormalities. Autosomal dominant, recessive and X-linked forms of HSP have been defined.
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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