DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for episodic ataxia, type 9 — 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 moduleEpisodic ataxia, type 9 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 episodic ataxia, type 9 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
sodium voltage-gated channel alpha subunit 2 (SCN2A) — SCN2A 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 3beta,14beta,17beta,25rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6J8E · 3.0 Å · ligand (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en (9Z9). Experimental structure, not a prediction.
What the evidence adds up to
A 1981 double-blind, triple-crossover trial of low-dose oral physostigmine in 21 patients with various inherited ataxias found the drug more effective than placebo overall (p < 0.05). Thirteen patients had consistent, statistically significant responses to physostigmine; 8 did not (χ² = 46.9, p < 0.0001). Only three patients improved on placebo. Responses did not correlate with age, sex, or severity of ataxia, and different aspects of ataxia improved in different patients. No subsequent trial of physostigmine in episodic ataxia type 9 specifically was identified in the provided abstracts.
The abstracts describe cerebellar ataxias as a broad category encompassing sporadic, inherited (autosomal recessive, autosomal dominant/spinocerebellar, episodic, X-linked), and acquired forms. A 2018 review of 63 ataxia patients found 27 sporadic, 22 genetic, and 14 acquired cases; the mean age at presentation was 24 years for genetic, 46 for acquired, and 53 for sporadic ataxia. No abstract mentions episodic ataxia type 9 by name, nor any drug tested specifically for that subtype. The 2011 review notes that ataxias are rare, etiologically heterogeneous, and that many patients remain poorly understood, with large numbers needed for trials and a need for cooperative efforts and novel trial designs.
What is still missing is any clinical trial data for episodic ataxia type 9 specifically. No abstract reports a trial enrolling patients with that confirmed genotype. The 2014 review of Friedreich ataxia trial requirements underscores the complexity of designing efficacy studies for rare ataxias, including the need for validated rating scales, biomarkers, and cardiac assessments, but no such framework has been applied to episodic ataxia type 9. Without a dedicated trial, patient stratification by genotype, and funding for a sufficiently powered study, no drug can be assessed for this condition.
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 · 2004 · 253 citations
Treatment of episodic ataxia type 2 with the potassium channel blocker 4-aminopyridine
AbstractPatients with episodic ataxia type 2 (EA2) can often be successfully treated with acetazolamide. The authors report three patients with EA2 (two with proven mutations in the CACNA1A gene) whose attacks were prevented with the potassium channel blocker 4-aminopyridine (4-AP; 5 mg tid). Attacks recurred after treatment was stopped; subsequent treatment alleviated the symptoms (mean follow-up time 6 months). These effects might be due to an improvement of the impaired functioning of Purkinje cells.
Current Opinion in Neurology · 2009 · 187 citations
Cerebellar ataxias
AbstractPURPOSE OF REVIEW: The term 'cerebellar ataxias' encompasses the various cerebellar disorders encountered during daily practice. Patients exhibit a cerebellar syndrome and can also present with pigmentary retinopathy, extrapyramidal movement disorders, pyramidal signs, cortical symptoms (seizures, cognitive impairment/behavioural symptoms), and peripheral neuropathy. The clinical diagnosis of subtypes of ataxias is complicated by the salient overlap of the phenotypes between genetic subtypes. The identification of the causative mutations of many hereditary ataxias and the development of relevant animal models bring hope for effective therapies in neurodegenerative ataxias. RECENT FINDINGS: We describe the current classification of cerebellar ataxias and underline the recent discoveries in molecular pathogenesis. Cerebellar disorders can be divided into sporadic forms and inherited diseases. Inherited ataxias include autosomal recessive cerebellar ataxias, autosomal dominant cerebellar ataxias/spinocerebellar ataxia) and episodic ataxias, and X-linked ataxias. From a motor control point of view, the leading theories of ataxia are based on neural representations or 'internal models' to emulate fundamental natural processes such as body motion. SUMMARY: Recent molecular advances have direct implications for research and daily practice. We provide a framework for the diagnosis of ataxias. For the first time, the therapeutic agents under investigation are targeted to deleterious pathways.
Double‐blind, triple‐crossover trial of low doses of oral physostigmine in inherited ataxias
AbstractThe signs of ataxia in patients with inherited ataxias have been reported to improve after single injections or single oral doses of physostigmine. To study this effect, 21 patients with various inherited ataxias underwent a randomized, double-blind, triple-crossover trial of physostigmine and inert placebo taken orally in low doses for four sequential 3-month periods. Overall, the drug was more effective than the placebo (<i>p</i> <0.051. Thirteen patients had consistent, statistically significant responses to physostigmine; 8 did not (x<sup>2</sup>=46.9, <i>p</i> <0.0001). Only three patients improved on placebo. Responses did not correlate with age, sex, or severity of ataxia. Some aspects of ataxia improved in some patients, other aspects in other patients. Preliminary accounts of this work were previously reported.1-2
Physical Therapy · 2007 · 30 citations · open access
Presentation and Progression of Friedreich Ataxia and Implications for Physical Therapist Examination
AbstractFriedreich ataxia, although rare, is the most prevalent inherited ataxia. Recent insight into the disease pathogenesis is creating new hope for effective therapies. The purposes of this update are: (1) to review the etiology, presentation, and progression of Friedreich ataxia and (2) to describe a comprehensive physical therapist examination emphasizing valid and reliable performance measurements associated with disease progression. Early identification of individuals with Friedreich ataxia and precise characterization of impairments and functional limitations gain importance as new drug therapies are considered.
Revista médica de Chile · 2018 · 6 citations · open access
Características clínicas de 63 pacientes con ataxia
AbstractBACKGROUND: Ataxia can be classified as genetic, sporadic or acquired. AIM: To report the clinical features of a group of patients with ataxia. MATERIAL AND METHODS: Review of medical records of patients consulting in a specialized center in movement disorders. Those records in which the diagnosis of "ataxia" or "ataxic syndrome" appeared, were selected for the review. RESULTS: Of 4,282 records surveyed, the diagnosis of ataxia appeared in 95. After eliminating repeated or incomplete records, 63 were reviewed. RESULTS: Ataxia was sporadic, genetic and acquired in 27, 22 and 14 patients, respectively. The mean age at presentation for genetic, acquired and sporadic ataxia was 24, 46 and 53 years respectively. All autosomal dominant ataxias were type 3 spinocerebellar ataxia (SCA). Friedrich's ataxia was the most common recessive form. Most sporadic forms of ataxia were multiple system atrophy with predominant cerebellar ataxia (MSA-C) subtype. CONCLUSIONS: Considering the heterogeneity of patients with ataxia, we propose a method to approach them.
Journal of Drug Delivery and Therapeutics · 2014 · 1 citations · open access
A REVIEW ON FRIEDREICH ATAXIA, A NEURODEGENERATIVE DISORDER
AbstractThe present report discusses about the clinical trial requirements for Friedreich ataxia disease such as inclusion and exclusion criteria for the patients,primary/secondary outcome measuresrequired for assessing the efficacy of therapies viarating scales, physical activity tests, biomarkersand number of subjects/patients to be enrolled in each phase of the clinical trials of Friedreich ataxia (F.A.). These parameters have been selected from the ongoing and completed clinical trials for F.A. as reported in Clinical trials.gov and Friedreich Ataxia Research Alliance (FARA) official website. A total of 33 clinical trialdetails werereviewed for compilation of the above mentioned parameters. For the purpose of this report, the most useful and most commonly assessedprimary/secondary outcome measureswith respect to efficacy as well as inclusion and exclusion criteria have been selected and are being cited in this review.The outcome measures for the purpose of efficacy trials can broadly be classified as primary and secondaryoutcome measures and in each category, subclasses are being presented in the order of their priority as determined by their usefulness and common occurrence in all trials mentioned. These outcome measuresincludeRating Scales for Friedreich Ataxia, Physical Activity Tests and Biomarkers, evaluation of Cardiac functionality viz. left ventricular wall mass, non-invasive measures of systolic and diastolic ventricular function, echocardiography and immunogenicity.The genetic predisposition of Friedreich ataxia (epigenetics) leading to the pathogenesis of the disease is also discussed in this report. Based on above primary and secondary outcomes measures and inclusion and exclusion criteria, a tabular representation of the ongoing/ completed clinical trials representing the efficacy studies of the test molecules and the patient involvements in each clinical trial is also been listed. Various aspects of clinical trialsneeded for assessing ataxic stage in Friedreich ataxia disease is been reviewed in this article. Key words:Friedreich ataxia, Friedreich Ataxia Research Alliance (FARA), Inclusion and Exclusion criteria, primary and secondary outcome measures, rating scales, biomarkers, physical activity tests.
AbstractAtaxias are rare diseases and the etiologic heterogeneity make individual entities even rarer. There are still substantial numbers of patients who are still poorly understood. Available assessment techniques still point to large numbers of patients needed for clinical trials and the need for cooperative efforts, better assessment tools and novel trial designs. Better understanding of neural circuitry abnormalities may lead to more effective symptomatic therapy. Opportunities exist for targeting at risk individuals for effective therapies but how this can be done is not clear. Preventive strategies may become feasible in many 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.
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