DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for spastic ataxia 1 — 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 moduleSpastic ataxia 1 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 spastic ataxia 1 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
In a 1981 double-blind, triple-crossover trial, 21 patients with various inherited ataxias received low-dose oral physostigmine or placebo for four sequential three-month periods. Overall, the drug was more effective than placebo (p < 0.051). Thirteen patients had consistent, statistically significant responses to physostigmine; eight 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. Some aspects of ataxia improved in some patients, other aspects in other patients.
A 1997 double-blind crossover study gave 19 patients with degenerative cerebellar diseases (11 with autosomal dominant cerebellar ataxia, 8 with idiopathic cerebellar ataxia) a transdermal physostigmine patch releasing about 6 mg over 24 hours or a placebo patch for four weeks each. Physostigmine patches had no significant effect on cerebellar symptoms. The authors concluded that treatment with physostigmine does not improve the conditions of patients with ataxia.
A 2022 systematic review and meta-analysis of seven randomised controlled trials involving 203 patients examined non-invasive electrical stimulation (NES) in neurodegenerative ataxia and spasticity. Significant improvements were seen in the Modified Ashworth Scale (mean difference −0.42, 95% CI −0.76 to −0.08, p = 0.015), cerebellar brain inhibition (mean difference −0.35%, 95% CI −0.42 to −0.28, p < 0.001), 8-metre walking time (mean difference −1.88 s, 95% CI −3.26 to −0.49, p = 0.008), International Cooperative Ataxia Rating Scale (mean difference −7.84, 95% CI −11.90 to −3.78, p < 0.001), and Scale for Assessment and Rating of Ataxia (mean difference −3.01, 95% CI −4.74 to −1.28, p < 0.001). No significant change was observed in the nine-hole peg test (mean difference −3.52 s, 95% CI −9.15 to 2.10, p = 0.220). No severe adverse effects were reported.
A 2025 study developed the Spastic Ataxia Composite (SPAXCOM) scale using longitudinal data from 127 SPG7 and 112 ARSACS patients. With seven items, the SPAXCOM showed an effect size of 0.71, higher than reference scales (SARA: 0.43, SPRS: 0.42, FARS-ADL: 0.27). It was more sensitive in participants with a SARA lower than 10 and within the intermediate disease stage. Perception of improvement, stagnation, and worsening were associated with a mean yearly SPAXCOM change of 0.44, 0.61, and 1.22, respectively. A 2024 study identified digital-motor candidate outcomes for SPG7 using wearable sensors, showing ability to discriminate patients from controls and correlation with patient-relevant health aspects even in mild disease stages, but these have not yet been validated longitudinally. A 2014 review of 33 clinical trials for Friedreich ataxia catalogued outcome measures and trial design parameters but did not report any treatment efficacy data. What remains missing for spastic ataxia 1 specifically is any dedicated trial funding, a validated outcome measure for that genotype, and any patient stratification strategy that might identify who could benefit from a given intervention.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
BMJ · 1971 · 122 citations · open access
Baclofen in the Treatment of Spasticity
AbstractBaclofendagger (Lioresal), a derivative of gamma-aminobutyric acid, was introduced in 1966 as a possible treatment for spasticity due to corticospinal tract lesions. Preliminary studies suggested that it may be more effective than other spasmolytic agents currently available, and a double-blind controlled trial in a group of 23 patients against placebo has shown it to be significantly more effective.
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
Double-blind Crossover Study With Physostigmine in Patients With Degenerative Cerebellar Diseases
AbstractOBJECTIVE: To determine whether treatment with physostigmine can improve the conditions of patients with ataxia. DESIGN: A double-blind crossover study with physostigmine was performed in 19 patients with degenerative cerebellar diseases. SETTING: Patients were selected from an ongoing prospective follow-up study at the university hospital in Lübeck, Germany. PATIENTS: Eleven patients with autosomal dominant cerebellar ataxia and 8 patients with idiopathic cerebellar ataxia. INTERVENTION: Physostigmine was administered by using a transdermal system (patch) containing 30 mg of physostigmine as a base, of which about 6 mg is released during 24 hours along a diffusion gradient. Each treatment phase with the physostigmine patch or the placebo lasted 4 weeks, after which the treatment of patients was crossed over to the other phase. MAIN OUTCOME MEASURES: Ataxia was documented and quantified by using a clinical score and posturographic measures. RESULTS: Physostigmine patches had no significant effect on cerebellar symptoms. CONCLUSION: Treatment with physostigmine does not improve the conditions of patients with ataxia.
Patient-Relevant Digital-Motor Outcomes for Clinical Trials in Hereditary Spastic Paraplegia Type 7
AbstractBACKGROUND AND OBJECTIVES: With targeted treatment trials on the horizon, identification of sensitive and valid outcome measures becomes a priority for >100 spastic ataxias. While digital-motor measures, assessed using wearable sensors, are considered prime outcome candidates for spastic ataxias, genotype-specific validation studies are lacking. We here aimed to identify candidate digital-motor outcomes for spastic paraplegia type 7 (SPG7)-one of the most common spastic ataxias-that (1) reflect patient-relevant health aspects, even in mild, trial-relevant disease stages; (2) are suitable for a multicenter setting; and (3) assess mobility also during uninstructed walking simulating real life. METHODS: ; Scale for the Assessment and Rating of Ataxia [SARA]) and the activities of daily living subscore of the Friedreich Ataxia Rating Scale (FARS-ADL). RESULTS: < 0.0001). DISCUSSION: We here identified trial-ready digital-motor candidate outcomes for the spastic ataxia SPG7 with proven multicenter applicability, ability to discriminate patients from controls, and correlation with measures of patient-relevant health aspects-even in mild disease stages. If validated longitudinally, these sensor outcomes might inform future natural history and treatment trials in SPG7 and other spastic ataxias.
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.
European Journal of Neurology · 2022 · 1 citations
Non‐invasive electrical stimulation in patients with neurodegenerative ataxia and spasticity: A systematic review and meta‐analysis of randomized controlled trials
AbstractAbstract Background and purpose There are limited treatment options for patients with neurodegenerative ataxia and spasticity. Non‐invasive electrostimulation (NES) is receiving increasing interest because of its ease of implementation, cost‐effectiveness and safety. A meta‐analysis was conducted to evaluate the efficacy of NES. Methods MEDLINE and Embase were screened for studies using NES in ataxias and spasticity. Key outcome measurements of effectiveness included changes in (1) Modified Ashworth Scale (MAS) scores, (2) cerebellar brain inhibition (CBI), (3) the nine‐hole peg test (9HPT), (4) the 8‐m walking time (8MWT), (5) International Cooperative Ataxia Rating Scale (ICARS) score and (6) the Scale for Assessment and Rating of Ataxia (SARA) scores. Results Seven randomized controlled trials involving 203 patients were included. There were significant improvements in MAS (mean difference [MD] −0.42, 95% confidence interval [CI] −0.76 to −0.08, p = 0.015), CBI (MD −0.35%, 95% CI −0.42 to −0.28, p < 0.001), 8MWT (MD −1.88 s, 95% CI −3.26 to −0.49, p = 0.008), ICARS (MD −7.84, 95% CI −11.90 to −3.78, p < 0.001) and SARA (MD −3.01, 95% CI −4.74 to −1.28, p < 0.001). There was almost no heterogeneity across all outcomes except for CBI ( I 2 = 79%). No significant changes in the 9HPT were observed comparing NES to a sham procedure (MD −3.52 s, 95% CI −9.15 to 2.10, p = 0.220). Most included studies were at low risk of bias, and no severe adverse effects were reported. Conclusion It was demonstrated that NES is an effective treatment for improving coordination and balance and increased exercise capacity in patients with ataxia and spasticity. There was also a significant modulation of CBI in ataxic patients.
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.
