DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for spastic ataxia 5 — 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 5 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 5 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
AFG3 like matrix AAA peptidase subunit 2 (AFG3L2) — AFG3L2 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 anpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6NYY · 3.0 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (ANP). Experimental structure, not a prediction.
What the evidence adds up to
A 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; 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, and different aspects of ataxia improved in different patients. No further controlled trials of physostigmine in spastic ataxia 5 have been reported.
A 2022 systematic review and meta-analysis of seven randomised controlled trials involving 203 patients with neurodegenerative ataxia and spasticity found that non-invasive electrical stimulation (NES) significantly improved Modified Ashworth Scale scores (mean difference −0.42), cerebellar brain inhibition (mean difference −0.35%), 8-metre walking time (mean difference −1.88 seconds), International Cooperative Ataxia Rating Scale scores (mean difference −7.84), and Scale for Assessment and Rating of Ataxia scores (mean difference −3.01). No significant change was seen in the nine-hole peg test (mean difference −3.52 seconds). Most studies had low risk of bias and no severe adverse effects were reported. The review did not specifically address spastic ataxia 5.
A 2025 multicentre 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 over two years, higher than reference scales (SARA 0.43, SPRS 0.42, FARS-ADL 0.27). The scale was more sensitive in participants with SARA below 10 and in intermediate disease stages. Perception of improvement, stagnation, and worsening corresponded to mean yearly SPAXCOM changes of 0.44, 0.61, and 1.22 respectively. This scale has not been validated in spastic ataxia 5.
What is missing for spastic ataxia 5 specifically: no dedicated clinical trial has been conducted for this genotype. The existing evidence comes from mixed ataxia populations or related disorders. No disease-modifying therapy has been tested in spastic ataxia 5. A validated outcome measure for this specific condition does not exist. Patient stratification by genetic subtype, natural history data, and funding for a targeted trial are all absent.
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 · 1981 · 37 citations
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
Advances in Therapies of Cerebellar Disorders: Immune-mediated Ataxias
AbstractThe identification of an increasing number of immune mediated ataxias suggests that the cerebellum is often a target organ for autoimmune insults. The diagnosis of immune mediated ataxias is challenging as there is significant clinical overlap between immune mediated and other forms of ataxia. Furthermore the classification of immune mediated ataxias requires further clarification particularly for those ataxias where no specific antigenic trigger and associated antibodies have been identified. Recognition of immune mediated ataxias remains imperative as therapeutic interventions can be effective, although given the relative rarity of this entity, large-scale treatment trials may not be feasible. This review will discuss advances in therapies for immune mediated ataxias based on what is currently available in the literature.
Progress in Rehabilitation Medicine · 2020 · 5 citations · open access
Feasibility Case Study for Treating a Patient with Sensory Ataxia Following a Stroke with Kinesthetic Illusion Induced by Visual Stimulation
AbstractBACKGROUND: Sensory ataxia is a disorder of movement coordination caused by sensory deficits, especially in kinesthetic perception. Visual stimulus-induced kinesthetic illusion (KINVIS) is a method used to provide vivid kinesthetic perception without peripheral sensory input by using a video showing pre-recorded limb movements while the actual limb remains stationary. We examined the effects of KINVIS intervention in a patient with sensory ataxia. CASE: The patient was a 59-year-old man with a severe proprioceptive deficit caused by left thalamic hemorrhage. During KINVIS intervention, a computer screen displayed a pre-recorded mirror image video of the patient's unaffected hand performing flexion-extension movements as if it were attached to the patient's affected forearm. Kinematics during the flexion-extension movements of the paretic hand were recorded before and after 20-min interventions. Transcranial magnetic stimulation was applied to the affected and non-affected hemispheres. The amplitude of the motor-evoked potential (MEP) at rest was recorded for the muscles of both hands. After the intervention, the total trajectory length and the rectangular area bounding the trajectory of the index fingertip decreased. The MEP amplitude of the paretic hand increased, whereas the MEP amplitude of the non-paretic hand was unchanged. DISCUSSION: The changes in kinematics after the intervention suggested that KINVIS therapy may be a useful new intervention for sensory ataxia, a condition for which few effective treatments are currently available. Studies in larger numbers of patients are needed to clarify the mechanisms underlying this therapeutic effect.
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.
AbstractThe cupboard is bare when it comes to the symptomatic treatment of ataxia. These authors report apparent success with varenicline, initially given for smoking cessation to a 64-year-old man with prominent ataxia due to fragile X tremor/ataxia syndrome (FXTAS), a 9-year history of tremor, and a 4-year history of gait ataxia with falling. After taking 1 mg of varenicline twice daily for 1 week, he noted a striking …
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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