DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Friedreich ataxia — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFriedreich ataxia maps to a 6-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 friedreich ataxia 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
interferon gamma receptor 2 (IFNGR2) — IFNGR2 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 cysdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5EH1 · 1.8 Å · ligand CYSTEINE (CYS). Experimental structure, not a prediction.
What the evidence adds up to
A phase 3 double-blind placebo-controlled trial of idebenone in 70 ambulatory paediatric Friedreich ataxia patients aged 8 to 18 years, with baseline International Cooperative Ataxia Rating Scale scores between 10 and 54, found no statistically significant difference between drug and placebo on neurological function over 24 weeks. Patients receiving idebenone improved by 2.5 points on the mean ICARS score from baseline, while the placebo group improved by 1.3 points. On the Friedreich Ataxia Rating Scale, the idebenone group improved by 1.6 points while the placebo group declined by 0.6 points. Neither difference reached statistical significance. The trial was registered at clinicaltrials.gov as NCT00537680.
Since the discovery of the causative mutation in 1996, a series of clinical trials have been conducted for Friedreich ataxia, but as of 2018 none had achieved regulatory approval. A review of trial design in the disease identified several shortcomings. Although two long-term natural history studies and a patient registry capturing more than 3000 potential subjects exist, trials have not consistently used this information. Studies have been smaller and shorter than natural history data suggest are needed, and have not always matched outcome measures to specific sub-cohorts or chosen subjects in the most responsive phases of the disease.
The disease itself is an autosomal recessive degenerative condition primarily affecting the nervous system and heart, originally described as a degenerative atrophy of the posterior columns of the spinal cord. The full phenotype and genetic epidemiology became clear only after direct genetic testing became available in 1996, and the complex pathogenesis is still being unravelled.
What remains missing are longer trials with more subjects, studies directed at optimal patient populations, and more extensive preclinical development to inform trial design. No drug has yet shown statistically significant improvement on neurological function in a phase 3 trial in Friedreich ataxia.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Neurology · 2010 · 225 citations · open access
A Phase 3, Double-blind, Placebo-Controlled Trial of Idebenone in Friedreich Ataxia
AbstractOBJECTIVE: To assess the efficacy of idebenone on neurological function in patients with Friedreich ataxia. DESIGN: Randomized, double-blind, placebo-controlled intervention trial. SETTING: Children's Hospital of Philadelphia and the University of California at Los Angeles. PARTICIPANTS: Seventy ambulatory pediatric patients (age, 8-18 years) with a baseline International Cooperative Ataxia Rating Scale (ICARS) score of 10 to 54. INTERVENTIONS: Participants were randomized into 1 of 3 treatment arms: 450 or 900 mg of idebenone per day (in those with a body weight < or = or >45 kg, respectively; n = 22); 1350 or 2250 mg of idebenone per day (n = 24); or placebo (n = 24). MAIN OUTCOME MEASURES: Mean change from baseline to week 24 in ICARS score was the primary efficacy variable. Mean change in Friedreich Ataxia Rating Scale (FARS) score, performance measures, and activities of daily living were the secondary efficacy variables. RESULTS: Patients who received idebenone improved by 2.5 points on mean ICARS score compared with baseline, while patients in the placebo group improved by 1.3 points. Patients who took idebenone also improved by 1.6 points on the FARS, while patients taking placebo declined by 0.6 points. For both end points, the difference between the idebenone and placebo groups was not statistically different. CONCLUSIONS: Idebenone did not significantly alter neurological function in Friedreich ataxia during the 6-month study. Larger studies of longer duration may be needed to assess the therapeutic potential of drug candidates on neurological function in Friedreich ataxia. Trial Registration clinicaltrials.gov Identifier: NCT00537680.
AbstractFriedreich ataxia is an autosomal recessive degenerative disease that primarily affects the nervous system and the heart. It is named after its original description as a "degenerative atrophy of the posterior columns of the spinal cord" by Nicholaus Friedreich, who was a professor of medicine in Heidelberg in the second half of the 19th century. The full extent of the Friedreich ataxia phenotype and its genetic epidemiology could only be appreciated after a direct genetic test became available in 1996. At the same time, the complex pathogenesis of Friedreich ataxia started to be unraveled. Herein, I review our current knowledge of the disease and how it is contributing to the development of therapeutic approaches.
Expert Opinion on Orphan Drugs · 2018 · 18 citations
Clinical trial design for Friedreich ataxia - Where are we now and what do we need?
AbstractIntroduction: Since the discovery of the mutation in Friedreich ataxia, a series of clinical trials have been conducted to provide symptomatic or disease-modifying therapy. At this point none have reached regulatory approval. This review examines several aspects of the design of FRDA clinical trials to understand better their shortcomings.Areas covered: The mechanisms for performing clinical trials have been well developed in FRDA, including the presence of two ongoing longterm natural history studies and a patient registry that captures more than 3000 potential subjects. Still, trials to this point have not utilized this information in many situations. Studies have been smaller and shorter than predicted based on natural history studies. In addition, studies have not always matched outcome measures to specific sub cohorts or chosen subjects in the most responsive phases of the disease.Expert opinion: The optimization of clinical trials in FRDA should lead to a greater likelihood of success. Such improvements should include longer studies with more subjects, and directing of studies to optimal populations. Along with more extensive preclinical development, improved design will facilitate future success in clinical trials in FRDA.
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.
