DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for spastic ataxia 2 — 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 moduleSpastic ataxia 2 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 spastic ataxia 2 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
kinesin family member 1C (KIF1C) — KIF1C 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 unxdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2G1L · 2.602 Å · ligand UNKNOWN ATOM OR ION (UNX). Experimental structure, not a prediction.
What the evidence adds up to
A 2011 review of degenerative ataxias noted that a phase 3 trial of idebenone in Friedreich ataxia failed, while a smaller phase 2 trial of riluzole in a mixed ataxia population suggested a possible antiataxic action. The same review stated that the methodological requirements to run large interventional trials are now met. A 2009 report described a single 64-year-old man with fragile X tremor/ataxia syndrome who noted a striking improvement in gait ataxia and falling after taking 1 mg of varenicline twice daily for one week, initially prescribed for smoking cessation.
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 some aspects of ataxia improved in some patients while other aspects improved in others.
A 2022 systematic review and meta-analysis of seven randomised controlled trials involving 203 patients evaluated non-invasive electrical stimulation (NES) in neurodegenerative ataxia and spasticity. Compared to sham procedures, NES produced significant improvements in the Modified Ashworth Scale (mean difference −0.42, 95% CI −0.76 to −0.08), cerebellar brain inhibition (mean difference −0.35%, 95% CI −0.42 to −0.28), 8-metre walking time (mean difference −1.88 seconds, 95% CI −3.26 to −0.49), the International Cooperative Ataxia Rating Scale (mean difference −7.84, 95% CI −11.90 to −3.78), and the Scale for Assessment and Rating of Ataxia (mean difference −3.01, 95% CI −4.74 to −1.28). No significant change was seen in the nine-hole peg test (mean difference −3.52 seconds, 95% CI −9.15 to 2.10). No severe adverse effects were reported. A 2020 case study of a single 59-year-old man with sensory ataxia from a thalamic haemorrhage reported that a single 20-minute session of visual stimulus-induced kinesthetic illusion reduced total trajectory length and rectangular area of index fingertip movement, and increased motor-evoked potential amplitude in the paretic hand.
What is still missing for spastic ataxia 2 specifically are any trials that enrol patients with that exact genetic diagnosis. The existing evidence comes from mixed ataxia populations, single case reports, or other conditions entirely. No drug has been tested in a dedicated, adequately powered trial for spastic ataxia 2. The necessary funding, a trial design that accounts for the rarity and slow progression of the disease, and reliable patient stratification by genetic subtype remain 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.
Current Opinion in Neurology · 2011 · 123 citations
Update on degenerative ataxias
AbstractPURPOSE OF REVIEW: Degenerative ataxias are a heterogeneous group of disorders that are clinically characterized by progressive ataxia. They can be subdivided into three major groups: the acquired ataxias, which are due to exogenous or endogenous nongenetic causes, the hereditary ataxias, and the nonhereditary degenerative ataxias. On the basis of a review of the literature published in 2009 and 2010, this review gives an update of the most recent developments in the field of ataxia. RECENT FINDINGS: Using advanced methods of molecular genetic analysis, novel genes for recessive and dominant ataxias were identified. Recent imaging studies in dominantly inherited spinocerebellar ataxias (SCAs) focussed on the analysis of connectivity in the brain. Novel clinical assessment methods were developed and validated in large patient cohorts. Although a phase 3 trial of idebenone in Friedreich ataxia (FRDA) failed, a smaller phase 2 trial of riluzole in a mixed population of ataxia patients suggested a possible antiataxic action of this compound. SUMMARY: Recent molecular advances underline the diversity of degenerative ataxias. With the progress in the development of clinical assessment methods for ataxia, the methodological requirements to run large interventional trials are now met.
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.
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.
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.
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.
