DeCure for Autosomal recessive spinocerebellar ataxia 15
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for autosomal recessive spinocerebellar ataxia 15 — 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 moduleAutosomal recessive spinocerebellar ataxia 15 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 autosomal recessive spinocerebellar ataxia 15 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
rubicon autophagy regulator (RUBCN) — RUBCN 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 gtpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6WCW · 2.8 Å · ligand GUANOSINE-5'-TRIPHOSPHATE (GTP). Experimental structure, not a prediction.
What the evidence adds up to
A 2001 report described a kindred with a dominantly inherited pure cerebellar ataxia after excluding known spinocerebellar ataxias at that time. Among eight subjects studied, the disease progressed slowly: the three least affected individuals had only mild gait ataxia after three or more decades of illness. The name spinocerebellar ataxia 15 was applied provisionally, pending identification of a chromosomal locus.
A 2005 review noted that molecular genetic research had uncovered much of the genetic basis for both autosomal dominant and recessive spinocerebellar ataxias, and had begun to reveal some of the pathophysiological pathways involved. The review also stated that the expanding number of genes and loci, together with the clinical heterogeneity of specific ataxia subtypes, complicated clinical management.
A 2011 review covering dominantly inherited spinocerebellar ataxias reported over 35 genetic subtypes. The more common ones were caused by expanded CAG repeats, but most of the recently identified subtypes resulted from conventional mutations. Genotype-phenotype correlations were clearest for repeat expansions, where repeat length partially explained age at onset, disease severity, progression, and core clinical phenotype. Common disease mechanisms appeared to include misfolding and aggregation, impairment of the protein quality control system, abnormal protein interactions, disruption of gene transcription, RNA toxicity, and changes in glutamate and calcium signalling. The review stated plainly that despite progress in molecular genetics and suggested pathways, no drug specifically designed for or targeted at these mechanisms was available.
What remains missing is any drug specifically developed for the mechanisms identified in spinocerebellar ataxia 15 or the other dominant ataxias. No clinical trial of a repurposed or novel agent for SCA15 has been reported. Patient stratification by genotype is possible for repeat-expansion subtypes but has not been applied to SCA15, whose genetic basis was not yet mapped in the abstracts provided. Funding for preclinical work and for trials that account for the slow progression and small kindred size is absent.
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 · 2001 · 83 citations
A new autosomal dominant pure cerebellar ataxia
AbstractA kindred is described with a dominantly inherited "pure" cerebellar ataxia in which the currently known spinocerebellar ataxias have been excluded. In the eight subjects studied, a notable clinical feature is slow progression, with the three least affected having only a mild degree of gait ataxia after three or more decades of disease duration. Pending an actual chromosomal locus discovery, the name spinocerebellar ataxia (SCA)15 is expectantly applied.
Recent Advances in Hereditary Spinocerebellar Ataxias
AbstractIn recent years, molecular genetic research has unraveled a major part of the genetic background of autosomal dominant and recessive spinocerebellar ataxias. These advances have also allowed insight in (some of) the pathophysiologic pathways assumed to be involved in these diseases. For the clinician, the expanding number of genes and genetic loci in these diseases and the enormous clinical heterogeneity of specific ataxia subtypes complicate management of ataxia patients. In this review, the clinical and neuropathologic features of the recently identified spinocerebellar ataxias are described, and the various molecular mechanisms that have been demonstrated to be involved in these disorders are discussed.
AbstractThe relevant clinical, genetic, and cell biologic aspects of the dominantly inherited spinocerebellar ataxias (SCAs) are reviewed in this article. SCAs are diseases of the entire nervous system; in addition to cerebellar ataxia, the central (but not obligate) disease feature, many noncerebellar complications can be present as well. There are over 35 genetic subtypes: although those caused by expanded CAG repeats are still the more common ones, the majority of the recent SCAs have been caused by more conventional mutations. Genotype-phenotype correlations do exist and are most clear for the repeat expansion, where repeat length partially explains age at onset, disease severity and progression, and the core clinical phenotype. Some common themes within the disease mechanisms seem to emerge, including misfolding and aggregation, impairment of the protein quality control system, abnormal protein interactions, disruption of gene transcription, RNA toxicity, and changes in glutamate and calcium signaling. Yet despite this exciting progress in the molecular genetic background and suggested corresponding pathways, there is still no drug available that is specifically designed for or targeted at the mechanisms at play.
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.
