DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for spinocerebellar ataxia type 1 — 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 moduleSpinocerebellar ataxia type 1 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 spinocerebellar ataxia type 1 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
brain derived neurotrophic factor (BDNF) — BDNF 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 ipadrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1BND · 2.3 Å · ligand ISOPROPYL ALCOHOL (IPA). Experimental structure, not a prediction.
What the evidence adds up to
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurological disorder caused by an expanded CAG trinucleotide repeat in the ataxin-1 gene, which encodes an expanded polyglutamine tract. The mutant protein acts in the nucleus, and the expansion alters the folding properties of ataxin-1. Several cellular pathways that can influence the disease process have been identified, but as of 2001 the pathogenic mechanism was still being characterised. No clinical trial data for SCA1 are reported in these abstracts.
A 2024 randomised, double-blind, placebo-controlled trial tested ganglioside GM1 pulse treatment in spinocerebellar ataxia type 3 (SCA3), a different subtype. Forty-eight patients with SCA3 were enrolled; 43 were included in the intention-to-treat analysis at 12 weeks. The high-dose GM1 group (400 mg then 200 mg daily for 4 weeks) showed a least-squares mean change in SARA score of −3.80 (SE 0.39; 95% CI −4.58 to −3.02) from baseline to 12 weeks post-treatment. The low-dose GM1 group showed a change of 0.34 (SE 0.40; 95% CI −0.46 to 1.13), and the placebo group a change of 0.73 (SE 0.40; 95% CI −0.07 to 1.52). Secondary outcomes including ICARS score, Barthel Index of ADL, and plasma and CSF GABA levels improved in the high-dose group compared to low-dose and placebo. All treatments were well tolerated.
These results apply only to SCA3, not to SCA1. The molecular mechanisms of SCA1 involve toxic protein effects in the nucleus and protein misfolding, but no drug has been tested in a controlled trial for SCA1 in the abstracts provided. What is missing is any clinical trial of a disease-modifying agent specifically for SCA1, along with the funding and patient stratification needed to design such a trial.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Neurology · 2007 · 151 citations
Spinocerebellar ataxias: an update
AbstractPURPOSE OF REVIEW: Here we discuss recent advances regarding the molecular genetic basis of dominantly inherited ataxias. RECENT FINDINGS: Important recent observations include insights into the mechanisms by which expanded polyglutamine causes cerebellar degeneration; new findings regarding how noncoding expansions may cause disease; the discovery that conventional (i.e. nonrepeat) mutations underlie recently identified ataxias; and growing recognition that multiple biological pathways, when perturbed, can cause cerebellar degeneration. SUMMARY: The dominant ataxias, also known as spinocerebellar ataxias, continue to grow in number. Here we review the major categories of spinocerebellar ataxias: expanded polyglutamine ataxias; noncoding repeat ataxias; and ataxias caused by conventional mutations. After discussing features shared by these disorders, we present recent evidence supporting a toxic protein mechanism for the polyglutamine spinocerebellar ataxias and the recognition that both protein misfolding and perturbations in nuclear events represent key events in pathogenesis. Less is known about pathogenic mechanisms in spinocerebellar ataxias due to noncoding repeats, though a toxic RNA effect remains possible. Newly discovered, conventional mutations in spinocerebellar ataxias suggest a wide range of biological pathways can be disrupted to cause progressive ataxia. Finally, we discuss how new mechanistic insights can drive the push toward preventive treatment.
SCA1 molecular genetics: a history of a 13 year collaboration against glutamines
AbstractSpinocerebellar ataxia type 1 (SCA1) is a relatively rare autosomal-dominant neurological disorder. SCA1 has the intriguing feature that the disease-causing mutation is the expansion of an unstable trinucleotide repeat, specifically a CAG repeat that encodes the amino acid glutamine in ataxin-1. During the past 10 years, substantial progress has been made towards understanding the pathogenic mechanism in this disease. The nucleus has been identified as the subcellular site where the mutant protein acts to cause disease. Evidence indicates that expansion of the glutamine tract alters the folding properties of ataxin-1. Finally, several cellular pathways have been identified which are able to impinge on the SCA1 disease process. The characterization of these pathways and their role in SCA1 will guide research over the next several years.
Movement Disorders · 2024 · 3 citations · open access
Potential Disease‐Modifying Effects of Ganglioside <scp>GM1</scp> Pulse Treatment on Spinocerebellar Ataxia Type 3, a Parallel‐Group, Double‐Blind, Randomized, Controlled Trial
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.
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