DeCure for Spinocerebellar ataxia, autosomal recessive 24
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for spinocerebellar ataxia, autosomal recessive 24 — 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 moduleSpinocerebellar ataxia, autosomal recessive 24 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
approvedVitamin EApproved drug
Structures already discussed alongside spinocerebellar ataxia, autosomal recessive 24 in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
First Structural Evidence of a Specific Inhibition of Phospholipase A2 by Vitamin E and its Implications in Inflammation: Crystal Structure of the Complex Formed between Phospholipase A2 and Vitamin E at 1.8 A Resolution. — Vitamin E has a real, experimentally solved structure in complex with this target (PDB 1KPM, 1.8 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet vitdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1KPM · 1.8 Å · ligand Vitamin E (VIT). Experimental structure, not a prediction.
What the evidence adds up to
The abstracts provided do not describe autosomal recessive spinocerebellar ataxia type 24. One 1998 report describes a family with a new type of familial spinocerebellar ataxia that resembles Friedreich’s ataxia, ataxia with vitamin E deficiency, and ataxia telangiectasia, but with elevated serum creatine kinase, gamma-globulin, and alpha-fetoprotein. Biochemical and genetic testing ruled out those three conditions and other familial spinocerebellar ataxias. No drug, treatment, or outcome data are given for that family.
A 2004 letter describes five patients with spinocerebellar ataxia type 2, confirmed by CAG repeat expansion at the SCA2 locus. Four of the five showed clinical improvement within one hour of taking 10 mg of zolpidem. No further details on duration, magnitude, or reproducibility of improvement are provided, and no controlled trial is reported.
A 2015 survival study of 446 cases with known mutations found median survival of 68 years (95% CI 65–70) in 223 patients with polyglutamine expansions versus 80 years (95% CI 73–84) in 23 patients with other mutations. At age 60, 30% of the polyglutamine group used wheelchairs versus 3% in the other group. That study covers dominant ataxias, not recessive type 24.
A 2011 review states that despite progress in identifying over 35 genetic subtypes of dominant ataxias and understanding mechanisms such as protein misfolding, impaired quality control, abnormal protein interactions, transcription disruption, RNA toxicity, and altered glutamate and calcium signalling, no drug specifically designed for those mechanisms is available. A 2005 review similarly notes that expanding genetic knowledge has complicated clinical management. A 2022 report describes a novel SPTBN2 missense variant in spinocerebellar ataxia type 5, a dominant form with pure cerebellar involvement, and a 2025 case report describes a 34-year-old with spinocerebellar ataxia type I where clinical symptoms preceded neuroimaging changes. None of these address autosomal recessive type 24.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Neurology · 1998 · 54 citations
Familial spinocerebellar ataxia with cerebellar atrophy, peripheral neuropathy, and elevated level of serum creatine kinase, γ‐globulin, and α‐fetoprotein
AbstractHere, we report a familial spinocerebellar ataxia (FSCA), which has clinical features similar to Friedreich's ataxia, an ataxia with isolated vitamin E deficiency, and ataxia telangiectasia. However, the serum levels of creatine kinase, gamma-globulin, and alpha-fetoprotein were elevated, and biochemical and genetic analyses ruled out diagnosis of these three ataxias as well as other FSCAs. Thus, this family is thought to have a new type of FSCA.
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.
Annals of Clinical and Translational Neurology · 2015 · 44 citations · open access
Survival and severity in dominant cerebellar ataxias
AbstractInherited spinocerebellar ataxias (SCAs) are known to be genetically and clinically heterogeneous. Whether severity and survival are variable, however, is not known. We, therefore, studied survival and severity in 446 cases and 509 relatives with known mutations. Survival was 68 years [95% CI: 65-70] in 223 patients with polyglutamine expansions versus 80 years [73-84] in 23 with other mutations (P < 0.0001). Disability was also more severe in the former: at age 60, 30% were wheelchair users versus 3% with other SCAs (P < 0.001). This has implications for genetic counseling and the design of therapeutic trials.
New England Journal of Medicine · 2004 · 43 citations · open access
Transient Improvement of Spinocerebellar Ataxia with Zolpidem
AbstractTo the Editor: There is currently no effective pharmacologic treatment for spinocerebellar ataxia. We describe a family of five patients, four of whom had clinical improvement within one hour after the ingestion of zolpidem (10 mg). The diagnosis of spinocerebellar ataxia type 2 was confirmed by molecular analysis. Analysis of DNA for CAG repeat expansions in the SCA1, 2, 3, 6, and 7 genes revealed expansion of CAG repeats at the SCA2 locus. Patient 1, a 49-year-old man with titubation, dizziness, and loss of balance from the age of 34 years, had deteriorating speech and handwriting. Cerebellar signs included moderate . . .
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.
Open Science Journal · 2022 · 1 citations · open access
Novel missense variant in SPTBN2 possibly associated with spinocerebellar ataxia type 5 presenting as Parkinson´s disease
AbstractSpinocerebellar ataxias are a heterogeneous group of neurodegenerative diseases. There are more than 40 subtypes described so far, being spinocerebellar ataxia type 5 (SCA5) a rare autosomal-dominant ataxia with pure cerebellum involvement. The gene responsible is the non-erythrocyte beta 2 spectrin gene (SPTBN2), encoding β-III spectrin, highly expressed in Purkinje cells. Onset is usually before 30 years, although it ranges from infancy to 70 years. The main clinical manifestations are limb and gait ataxia (> 90%); however, some patients also show trunk ataxia, sensory deficits, abnormal eye movements, dysarthria, and hyperactive deep tendon reflexes (25–90%).
South Russian Journal of Therapeutic Practice · 2025 · 1 citations · open access
A familial case of spinocerebellar attack type I. Clinical and diagnostic parallels
AbstractSpinocerebellar ataxia is a neurodegenerative disease with an autosomal dominant type of inheritance, rapid progression of clinical manifestations with onset at a young age. The clinical case of a 34-year-old patient with spinocerebellar ataxia type I, burdened by a hereditary history and the formation of the anticipation phenomenon, is considered. It was noted thatclinical symptoms preceded neuroimaging data.
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.
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.
