DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for spinocerebellar ataxia type 4 — screening already-approved drugs against its 2-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 4 maps to a 2-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 4 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
No disease-modifying therapy has been established for spinocerebellar ataxia type 4 or any spinocerebellar degeneration. As of 2023, only symptomatic therapy is available. Taltirelin and protirelin are drugs covered by health insurance for cerebellar ataxia symptoms in some settings, and are expected to suppress symptom progression, but no controlled trial data for SCA4 specifically are reported. Muscle relaxants are used for spasticity, but no efficacy numbers for SCA4 are given in the literature reviewed.
A 2007 review notes that spinocerebellar ataxias continue to grow in number and that multiple biological pathways can be disrupted to cause progressive ataxia. For the polyglutamine SCAs, evidence supports a toxic protein mechanism, with protein misfolding and perturbations in nuclear events as key events in pathogenesis. For noncoding repeat ataxias, a toxic RNA effect remains possible. SCA4 is not mentioned by name in that review, and no drug target specific to SCA4 is identified.
A 2003 review states that in the previous 25 years there had been at most 18 controlled class 1 trials for ataxia, focusing on neurotransmitter mechanisms, and that there were no FDA-approved drugs for any SCA. Current treatment practices encompass rehabilitation interventions and off-label use of symptomatic medications. A 2013 review of physical therapy for spinocerebellar ataxia found 13 studies reporting improvement of symptoms, but noted methodological limitations and the need for greater rigour in future research.
What is still missing: a specific molecular diagnosis for SCA4 in most cohorts, any controlled trial of a drug in SCA4 patients, validated biomarkers for the disease, a universally accepted rating scale for clinical trials in the SCAs, and funding for a disease-modifying trial that stratifies patients by the SCA4 mutation.
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.
Expert Opinion on Pharmacotherapy · 2003 · 4 citations
Spinocerebellar degeneration
AbstractThe spinocerebellar degenerations/ataxias (SCAs) are a diverse group of rare, slowly progressive, neurological diseases, often inherited but of incompletely understood pathophysiology, which affect the cerebellum and its related pathways. They have few animal models and share no reliable biomarkers. They have, as yet, no universally validated rating scale for use in clinical trials. In the past 25 years, there have been, at most, 18 controlled (Class 1) trials for ataxia, which have focused on neurotransmitter mechanisms. There is currently only one National Institute of Neurological Disorders and Stroke-sponsored drug trial for ataxia (Phase I study of idebenone in Friedreich's ataxia). There are, as yet, no FDA-approved drugs for SCA. Current treatment practices encompass rehabilitation interventions and off-label use of symptomatic medications [1,2].
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · 1976 · 4 citations · open access
Design of the Investigation
AbstractThe general outline of the complete prospective study of 50 cases of spino-cerebellar degeneration is given. The general protocol followed, the criteria for inclusion and the mode of analysis are described. The aim of this study was to establish a base of clinical, physiological and biochemical facts upon which a logical and systematic approach to pathogenesis and treatment of Friedreich's ataxia could be attempted.
Revista Neurociências · 2013 · 3 citations · open access
Atendimento Fisioterapêutico para Indivíduos com Ataxia Espinocerebelar: Uma Revisão da Literatura
AbstractThe spinocerebellar ataxia (SCA) is a disorder characterized by deficits in the execution of coordinated movements with progressive postural sway associated with difficulty in maintaining balance and various other motor disorders. The gait may be ataxic, with broadening the base of support, instability, irregular steps and slow, lateropulsion and trembling in range of motion, so that physical therapy is an important alternative for the improvement of the disorders of this pathology. Objective. Make, based on scientific literature, a review of physical therapy strategies in the treatment of spinocerebellar ataxia. Method. The study researches the databases Medline and SciELO from 2001 to 2011, considering the following keywords: ataxia espinocerebelar, Fisioterapia, tratamento, reabilitação and its correlates in English. Results. We found 33 studies that had as its main theme ataxia, 20 articles were excluded because they did not report the physical therapy approach for this type of pathology. After review, 13 references were used. Conclusions. After this study, the importance of physical therapy in the treatment of patients with SCA becomes obvious, according to the benefits promoted, as all studies found an improvement of symptoms of this pathology. Methodological limitations observed suggest the need for greater rigor in future research.
AbstractNo disease-modifying therapy has been established for spinocerebellar degeneration and multiple system atrophy, and only symptomatic therapy is currently available. Taltirelin and protirelin are drugs covered by health insurance for cerebellar ataxia symptoms, and are expected to suppress the progression of symptoms. Muscle relaxants are used for spasticity associated with spinocerebellar degeneration, and vasopressors and therapeutic agents for dysuria are used for autonomic symptoms of multiple system atrophy. It is necessary to develop a new therapeutic agent with a different mechanism of action, aimed specifically at modifying the disease progression in patients with spinocerebellar degeneration and multiple system atrophy.
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 ;
Yakut Medical Journal · 2025 · 0 citations · open access
Approaches to the treatment of autosomal-dominant spinocerebellar ataxias
AbstractThe article is devoted to the prospects for the treatment of neurodegenerative diseases with dynamic mutations based on published studies of the search for approaches to the treatment of spinocerebellar ataxia. Although these diseases are incurable, research results show that certain medications and physical therapy can alleviate the symptoms of cerebellar ataxia. Due to the progress made in the study of spinocerebellar ataxia in recent years, there are high hopes that it will be possible to develop gene therapy methods that will slow down the progression of the disease or even stop its development.
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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