DeCure for Autosomal recessive spinocerebellar ataxia 13
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for autosomal recessive spinocerebellar ataxia 13 — 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 13 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 13 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
glutamate metabotropic receptor 1 (GRM1) — GRM1 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 ggldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9WQO · 2.9 Å · ligand GAMMA-L-GLUTAMIC ACID (GGL). Experimental structure, not a prediction.
What the evidence adds up to
No abstract in the provided set reports a clinical trial, a tested drug, or any measured outcome in patients with autosomal recessive spinocerebellar ataxia 13. The abstracts instead review the genetics and pathophysiology of spinocerebellar ataxias broadly. One 2011 review states that despite progress in identifying molecular mechanisms — including protein misfolding, impaired protein quality control, abnormal protein interactions, disrupted transcription, RNA toxicity, and altered glutamate and calcium signalling — no drug specifically designed for or targeted at those mechanisms is available. A 2012 review on spinocerebellar ataxia type 3, a dominant polyglutamine disorder, describes how mutant ataxin-3 forms aggregates, compromises transcription, overwhelms protein degradation, and interferes with cellular metabolism and transport, eventually leading to cell apoptosis. That same review offers no treatment data.
The 2005 and 2000 reviews note the clinical and genetic heterogeneity of the ataxias and the difficulty this creates for management. Prevalence estimates for familial spinocerebellar degenerations range from 1.5 to 22.1 per 100,000. No abstract mentions autosomal recessive spinocerebellar ataxia 13 by name, nor does any abstract report a drug repurposing attempt, a response rate, a survival figure, or a sample size for any intervention in any ataxia subtype.
What is still missing is any clinical trial testing a repurposed drug in autosomal recessive spinocerebellar ataxia 13, any patient stratification by genetic subtype, and the funding needed to move from mechanistic reviews to interventional studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
AbstractThe familial spinocerebellar degenerations are a heterogeneous group of disorders with onset in both childhood and adulthood. Their prevalence is estimated to be between 1.5 and 22.1 per 100,000. Although pathologic and clinical classification systems have been proposed in the past, all have had shortcomings. In the past several years, great strides in genetics have radically changed our thinking about the classification, and thus clinical presentation, of these disorders. In this chapter, we concentrate on the adult-onset familial ataxias.
The toxic effect of expanded ataxin-3 in spinocerebellar ataxia type 3
AbstractThe spinocerebellar ataxia·type 3 (SCA3),which belongs to the group of polyglutamine repeat (polyQ) diseases,is the most frequent form among the autosomal dominantly inherited spinocerebellar ataxias in China.Ataxin-3,encoded by SCA3 gene ( atxn3 ),is a ubiqitin-bingding protein and involved in mornitoring the degenaration of proteins by its deubiquitylation activity.The expanded ataxin-3 is of aggregative potential and forms aggresomes or inclusions by recruiting other proteins.The mutant ataxin-3 compromises the regulation of transcription,challenges the cell ' s ability to keep up with protein degradation,interferes with cellular metabolism and transportion,and eventually leads to cell apoptosis.This review will focus on emerging concepts of PolyQ disease,emphasizing the pathogenesis of SCA3.
Key words:
Spinocerebellar ataxia ; Ataxin-3 ; Pathogenesis
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.
