DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for cerebellar ataxia — screening already-approved drugs against its 45-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCerebellar ataxia maps to a 45-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 cerebellar 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
hydroxymethylbilane synthase (HMBS) — HMBS 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 2-hydroxy-2-oxoethyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7AAK · 1.7 Å · ligand 3-[4-(2-hydroxy-2-oxoethyl)-5-[[4-(2-hydroxy-2-oxoethyl)-5-[[4-(2-hydroxy-2-oxoethyl)-5-[[4-(2-hydroxy-2-oxoethyl)-3-(3-hydroxy-3-oxopropyl)-5-methyl-1~{H}-pyrrol-2-yl]methyl]-3-(3-hydroxy-3-oxopropyl)-1~{H}-pyrrol-2-yl]methyl]-3-(3-hydroxy-3-oxopropyl)-1~{H}-pyrrol-2-yl]methyl]-1~{H}-pyrrol-3-yl]propanoic acid (7J8). Experimental structure, not a prediction.
What the evidence adds up to
Cerebellar ataxia covers a heterogeneous group of inherited and sporadic disorders. The 2018 review notes that the pathophysiology is increasingly understood and that novel genes for dominant and recessive ataxias continue to be identified, but a sizeable proportion of patients still have no known cause for their disease. The rarity and restricted geographical distribution of some ataxias compound this problem. Large collaborative studies are providing information on clinical spectrum, progression, and pathophysiology, but the field faces challenges in translational research and development of successful therapies.
A 2008 case report describes a 65-year-old woman with stage IV colorectal cancer who developed persistent but reversible cerebellar ataxia while receiving capecitabine. Ataxia appeared on day 12 of the fourth treatment cycle, worsened through the fifth cycle, and by the seventh cycle she could not walk without assistance. Brain MRI showed no metastasis or cerebellar abnormality. Chemotherapy was postponed for six weeks until ataxia completely resolved; her neurologic symptoms did not recur after chemotherapy was ultimately discontinued due to disease progression.
A 2017 rat study examined Purkinje cell firing patterns in a 3-acetylpyridine model of ataxia and after treatment with riluzole. In normal rats, sodium firing frequency was approximately 22.53±5.49 Hz and calcium frequency 4.22±2.02 Hz. In ataxic rats, sodium frequency dropped to 6.46±0.23 Hz and calcium frequency to 1.52±1.19 Hz. In riluzole-treated rats, sodium frequency rose to 31.34±4.07 Hz and calcium frequency to 3.88±1.37 Hz. Computational modelling suggested that blockade of calcium-activated potassium channels produced power spectral density changes similar to those seen in ataxia. The authors conclude these alterations may be a basis for developing possible new treatment strategies.
What is still missing: the 2018 review makes clear that for most inherited ataxias the underlying cause remains unknown in many patients, and that rarity and geographical restriction hinder research. The capecitabine case is a single report of drug-induced ataxia, not a treatment. The riluzole rat study shows electrophysiological changes but provides no data on motor function, survival, or any clinical outcome in humans. No large, randomised, placebo-controlled trial of any drug for cerebellar ataxia is described in these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical and Translational Neuroscience · 2018 · 51 citations · open access
Epidemiology of inherited cerebellar ataxias and challenges in clinical research
AbstractCerebellar ataxia is a clinically heterogeneous group of disorders, which includes several well-characterized genetic diseases as well as sporadic ataxias. The pathophysiology of ataxia is being understood, and a mechanistic basis for the appearance of these disorders is progressively emerging. Novel genes associated with dominant and recessive ataxias are being steadily identified, and research on their pathomechanisms not only has led to understanding the etiology and underlying cause for the development of ataxia but also has steered the field towards future therapeutic regime, aiming to control and prevent some forms of these diseases. Nevertheless, lack of knowledge for the causation of disease in a sizeable proportion of patient remains, and this issue is further compounded by the rarity of some of these ataxias as well as their restricted geographical distribution. On the other hand, large collaborative studies are providing critical information on the clinical spectrum, progression, and pathophysiology of inherited and sporadic ataxias. In the following sections, we describe the epidemiology, symptoms, pathological progression, and clinical management of various forms of inherited cerebellar ataxias. Finally, we provide a perspective on the challenges faced by the field in translational research and the development of successful therapeutic modalities for patients.
American Journal of Health-System Pharmacy · 2008 · 8 citations
Capecitabine-associated cerebellar ataxia
AbstractPURPOSE: A case of capecitabine-associated cerebellar ataxia is presented. SUMMARY: A 65-year-old white woman with stage IV colorectal cancer with liver metastasis was started on a chemotherapy regimen of capecitabine, oxaliplatin, and bevacizumab, given every three weeks. She tolerated the first two treatment cycles fairly well without major toxicities. The capecitabine dosage was started at 2000 mg daily for 14 days during the first cycle and increased to 2500 and 3000 mg daily during the second and the third cycles, respectively. On day 5 of the third cycle, the patient reported increased nausea, fatigue, and sleepiness, and the dosage of capecitabine was subsequently reduced to 2500 mg daily. On day 12 of the fourth treatment cycle, she reported ongoing lightheadedness and progressive gait disturbance with worsening ataxia over the past 3 days. Her capecitabine dosage was further reduced to 2000 mg daily, and the time between treatment intervals was increased to four weeks. The patient continued to experience intermittent, but less severe, ataxia during the fifth treatment cycle. On the day before the seventh cycle was to begin, she had ataxic gait and could not walk without assistance. Subsequent magnetic resonance imaging of the brain revealed no evidence of brain metastasis or cerebellar abnormality. The chemotherapy was postponed for a total of six weeks until the ataxia completely resolved. Her chemotherapy was ultimately discontinued due to disease progression. Her neurologic symptoms did not recur. CONCLUSION: A patient receiving capecitabine-containing chemotherapy developed persistent but reversible cerebellar ataxia.
Basic and Clinical Neuroscience Journal · 2017 · 3 citations · open access
Power Spectral Density Analysis of Purkinje Cell Tonic and Burst Firing Patterns From a Rat Model of Ataxia and Riluzole Treated
AbstractINTRODUCTION: Purkinje Cell (PC) output displays a complex firing pattern consisting of high frequency sodium spikes and low frequency calcium spikes, and disruption in this firing behavior may contribute to cerebellar ataxia. Riluzole, neuroprotective agent, has been demonstrated to have neuroprotective effects in cerebellar ataxia. Here, the spectral analysis of PCs firing in control, 3-acetylpyridine (3-AP), neurotoxin agent, treated alone and riluzole plus 3-AP treated were investigated to determine changes in the firing properties. Difference in the power spectra of tonic and burst firing was assessed. Furthermore, the role of calcium-activated potassium channels in the power spectra was evaluated. METHODS: Analysis was performed using Matlab. Power spectral density (PSD) of PCs output were obtained. Peak frequencies were extracted from the spectrum and statistical comparisons were done. In addition, a multi-compartment computational model of a Purkinje cell was used. This computational stimulation allowed us to study the changes in the power spectral density of the PC output as a result of alteration in ion channels. RESULTS: Spectral analysis showed that in the spectrum of tonic and burst firing pattern only high sodium frequency and low calcium frequency was seen, respectively. In addition, there was a significant difference between the frequency components of PCs firing obtained from normal, ataxia and riluzole treated rats. Results indicated that sodium firing frequency of normal, ataxic and treated PCs occurred in approximate frequency of 22.53±5.49, 6.46±0.23, and 31.34±4.07 Hz, respectively; and calcium frequency occurred in frequency of 4.22±2.02, 1.52±1.19, and 3.88±1.37 Hz, respectively. The simulation results demonstrated that blockade of calcium-activated potassium channels in the PC model changed the PSD of the PC model firing activity. This change was similar to PSD changes in ataxia condition. CONCLUSION: These alterations in the spectrum of PC output may be a basis for developing possible new treatment strategies to improve cerebellar ataxia.
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.
