DeCure for Autosomal recessive spinocerebellar ataxia 10
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for autosomal recessive spinocerebellar ataxia 10 — 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 10 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 10 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
anoctamin 10 (ANO10) — ANO10 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 2rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5OC9 · 3.2 Å · ligand (2R)-2,3-dihydroxypropyl (7Z)-hexadec-7-enoate (79M). Experimental structure, not a prediction.
What the evidence adds up to
The 2006 study on spinocerebellar ataxia type 10 (SCA10) found that the mutant ATXN10 allele is transcribed at a normal level and that pre-mRNA containing the expanded ATTCT repeat is processed normally in patient-derived cells. Mice completely lacking the Sca10 gene died before birth, while heterozygous mice were overtly normal and did not develop any SCA10 phenotype. The authors concluded that neither a simple gain of function nor a simple loss of function of ATXN10 is likely to be the major pathogenic mechanism in SCA10. No drug or treatment was tested in this study.
A 2024 review of hereditary spinocerebellar degeneration states that no effective treatment is available for the condition. That review covers spinocerebellar degeneration broadly, not SCA10 specifically, and mentions no drug that has shown efficacy. A 2000 review notes that prevalence estimates for familial spinocerebellar degenerations range from 1.5 to 22.1 per 100,000, and a 2008 review reports that nearly 30 mutated genes associated with various subtypes have been located, most involving abnormal trinucleotide repeat expansion. Neither of these reviews reports any treatment.
No clinical trial data for any drug in SCA10 were provided. What is missing is any evidence of a therapeutic intervention tested in patients or animal models of SCA10, any validated biomarker for the disease, and any understanding of the molecular pathway that could be targeted. Without a clear pathogenic mechanism and without funding for preclinical drug screening or patient stratification tools, no rational drug-repurposing candidate can be proposed from these 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 · 2006 · 62 citations
The role of ataxin 10 in the pathogenesis of spinocerebellar ataxia type 10
AbstractBACKGROUND: Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder characterized by cerebellar ataxia and seizures. SCA10 is caused by an expansion of an ATTCT pentanucleotide repeat in intron 9 of the ataxin 10 (ATXN10) gene encoding an approximately 55-kd protein of unknown function. However, how this mutation leads to SCA10 is unknown. METHODS: In an effort to understand the pathogenic mechanism of SCA10, the authors conducted a series of experiments to address the effect of repeat expansion on the transcription and RNA processing of the ATXN10 gene. In addition, we generated Sca10 (mouse ataxin 10 homolog)-null mice and addressed the role of Sca10 gene dosage on the cerebellum. RESULTS: Mutant ATXN10 allele is transcribed at the normal level, and the pre-mRNA containing an expanded repeat is processed normally in patient-derived cells. Sca10-null mice exhibited embryonic lethality. Heterozygous mutants were overtly normal and did not develop SCA10 phenotype CONCLUSION: A simple gain of function or loss of function of ATXN10 is unlikely to be the major pathogenic mechanism contributing to the spinocerebellar ataxia type 10 phenotype.
Rinsho Shinkeigaku · 2024 · 1 citations · open access
Recent clinical advances in hereditary spinocerebellar degeneration
AbstractSpinocerebellar degeneration (SCD) is a neurodegenerative disorder characterized by cerebellar ataxia and other multisystem manifestations, such as Parkinsonism and pyramidal tract symptoms. No effective treatment is available for SCD. Approximately one-third of the cases of SCD are inherited, and the remaining two-third are sporadic, including multiple system atrophy. This article provides an overview of hereditary SCD, its clinical features, recent treatment advances, biomarkers, role of genomic medicine, and future treatment prospects.
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.
Advance in Molecular Genetics on Spinocerebellar Ataxia
AbstractSpinocerebellar ataxia is a group of autosomal dominant and heterogeneous neurodegenerative disease. Different genetic mutation may cause different subtypes of spinocerbellar ataxia. Up to now, with the rapid development of molecular genetic study, nearly 30 mutated genes associated with various subtypes of spinocerebella ataxias have been located and some of them have been identified. Most of the mutated genes are caused by the abnormal expansion of trinucleotide. In this review, the clinical and genetic features of the recently identified spinocerebellar ataxias will be described.
Key words:
Spinocerebellar ataxia ; Trinucleotide repeated expansion ; Molecular genetics ;
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.
