DeCure for Autosomal recessive spinocerebellar ataxia 12
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for autosomal recessive spinocerebellar ataxia 12 — 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 12 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 12 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.
What the evidence adds up to
A 2024 open-label study of nilotinib in autosomal dominant spinocerebellar ataxia included 32 subjects (median age 42, 56.2% female) treated at 150–300 mg/day for one year. The overall Scale for the Rating and Assessment of Ataxia (SARA) score at 12 months did not significantly improve, but 20 of 32 subjects (62.5%) were categorised as responsive, defined as any reduction in SARA score at 12 months. Pretreatment serum proteomic analysis of the five subjects with the highest and five with the lowest SARA change, plus five non-ataxia controls, identified four differentially expressed proteins: leucine-rich alpha-2-glycoprotein (LRG1), vitamin-D binding protein (DBP), and C4b-binding protein (C4BP) beta and alpha chains, all linked to autophagy. The authors present this as preliminary evidence that nilotinib might improve ataxia in some patients, with serum markers as a possible predictor of response. The trial is registered as NCT03932669.
The two review papers provide no clinical outcome data. A 2005 review describes the genetic and clinical heterogeneity of hereditary spinocerebellar ataxias, including autosomal recessive forms, and notes the difficulty this poses for clinical management. A 2022 review focuses on the mGluR1-PKCγ signalling pathway as a potential convergent pathogenic mechanism across spinocerebellar ataxias, discussing SCA-associated gene function during cerebellar Purkinje cell development, but offers no therapeutic results.
No abstract in this set concerns autosomal recessive spinocerebellar ataxia 12 specifically. The nilotinib study enrolled autosomal dominant disease, and its positive signal is confined to a subset of patients without a statistically significant group-level benefit. The proteomic finding is based on only ten treated subjects and five controls, with no validation cohort. What is missing is any trial in recessive ataxia 12, a larger randomised placebo-controlled design for nilotinib, and confirmation that the proposed serum protein markers predict response prospectively rather than retrospectively.
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.
International Journal of Molecular Sciences · 2022 · 13 citations · open access
The Emerging Key Role of the mGluR1-PKCγ Signaling Pathway in the Pathogenesis of Spinocerebellar Ataxias: A Neurodevelopmental Viewpoint
AbstractSpinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal dominantly inherited progressive disorders with degeneration and dysfunction of the cerebellum. Although different subtypes of SCAs are classified according to the disease-associated causative genes, the clinical syndrome of the ataxia is shared, pointing towards a possible convergent pathogenic pathway among SCAs. In this review, we summarize the role of SCA-associated gene function during cerebellar Purkinje cell development and discuss the relationship between SCA pathogenesis and neurodevelopment. We will summarize recent studies on molecules involved in SCA pathogenesis and will focus on the mGluR1-PKCγ signaling pathway evaluating the possibility that this might be a common pathway which contributes to these diseases.
Scientific Reports · 2024 · 3 citations · open access
Nilotinib treatment outcomes in autosomal dominant spinocerebellar ataxia over one year
Abstract) in patients with autosomal dominant spinocerebellar ataxia (ADSCA) and the factors associated with responsiveness. From an institutional cohort, patients with ADSCA who completed a 1-year treatment with nilotinib (150-300 mg/day) were included. Ataxia severity was assessed using the Scale for the Rating and Assessment of Ataxia (SARA), scores at baseline and 1, 3, 6, and 12 months. A subject was categorized 'responsive' when the SARA score reduction at 12 M was > 0. Pretreatment serum proteomic analysis included subjects with the highest (n = 5) and lowest (n = 5) SARA score change at 12 months and five non-ataxia controls. Thirty-two subjects (18 [56.2%] females, median age 42 [30-49.5] years) were included. Although SARA score at 12 M did not significantly improve in overall population, 20 (62.5%) subjects were categorized as responsive. Serum proteomic analysis identified 4 differentially expressed proteins, leucine-rich alpha-2-glycoprotein (LRG1), vitamin-D binding protein (DBP), and C4b-binding protein (C4BP) beta and alpha chain, which are involved in the autophagy process. This preliminary data suggests that nilotinib might improve ataxia severity in some patients with ADSCA. Serum protein markers might be a clue to predict the response to nilotinib.Trial Registration Information: Effect of Nilotinib in Cerebellar Ataxia Patients (NCT03932669, date of submission 01/05/2019).
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.
