DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for spinocerebellar ataxia type 23 — 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 moduleSpinocerebellar ataxia type 23 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 spinocerebellar ataxia type 23 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
glutamate ionotropic receptor delta type subunit 2 (GRID2) — GRID2 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9NWO · 3.57 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Spinocerebellar ataxia type 23 is one of a group of rare, slowly progressive neurological diseases with incompletely understood pathophysiology, no reliable biomarkers, and no universally validated rating scale for clinical trials. As of 2003, only 18 controlled Class 1 trials for ataxia had been conducted in the preceding 25 years, all focused on neurotransmitter mechanisms, and there were no FDA-approved drugs for any spinocerebellar ataxia. The only National Institute of Neurological Disorders and Stroke-sponsored drug trial at that time was a Phase I study of idebenone in Friedreich’s ataxia, not in spinocerebellar ataxia type 23. Current treatment consisted of rehabilitation and off-label symptomatic medications.
A 2013 review of physical therapy for spinocerebellar ataxia identified 33 studies on ataxia, of which 13 reported a physical therapy approach. All 13 found improvement in symptoms, but the review noted methodological limitations and called for greater rigour in future research. No drug trial was described in that review.
A 2023 review stated that no disease-modifying therapy has been established for spinocerebellar degeneration or multiple system atrophy. Only symptomatic therapy is available. In Japan, taltirelin and protirelin are health-insurance-covered drugs for cerebellar ataxia symptoms and are expected to suppress symptom progression. Muscle relaxants are used for spasticity, and vasopressors and drugs for dysuria are used for autonomic symptoms in multiple system atrophy. The review concluded that a new therapeutic agent with a different mechanism of action, aimed specifically at modifying disease progression, is needed.
What is still missing for spinocerebellar ataxia type 23 specifically: no disease-modifying drug has been tested in a controlled trial for this subtype; no reliable biomarkers or validated rating scales exist to measure progression or response; and no trial has been funded or designed that stratifies patients by the underlying TDP1 mutation. The evidence base remains limited to symptomatic management and physical therapy, with no drug repurposing data yet available for this exact genetic form.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neuropediatrics · 2002 · 111 citations
Friedreich's Ataxia: Idebenone Treatment in Early Stage Patients
AbstractBACKGROUND: Antioxidant therapy has been applied to Friedreich's ataxia patients. We assessed the effect of idebenone treatment in patients with Friedreich's ataxia. DESIGN: open-label trial. Nine Friedreich's ataxia patients (age range 11 - 19 years) were treated with idebenone (5 mg/kg/day). Patients were evaluated before the start of the therapy and throughout one year of treatment by International Cooperative Ataxia Rating Scales (ICARS) scores, neurophysiological investigations and echocardiographic measurements. Serum idebenone concentrations were measured by HPLC with electrochemical detection. The number of GAA repeats at the frataxin gene was analyzed by PCR. RESULTS: Serum idebenone concentrations ranged between 0.04 - 0.37 micro mol/L. Significantly positive correlation was observed between idebenone values and the percentage of difference between the ICARS scores before and 12 months after the start of the therapy (r = 0.883; p = 0.002). Significant reduction was observed comparing the ICARS scores in baseline conditions and after 3 months of treatment (p = 0.017). No differences were observed in echocardiographic measurements after the start of the therapy. CONCLUSIONS: Cerebellar improvement was notable in mild patients after the first 3 months of therapy. Idebenone treatment at early stages of the disease seems to reduce the progression of cerebellar manifestations. Further blind trials with a greater number of patients and higher doses are needed to fully assess the therapeutic potential of idebenone in Friedreich's ataxia.
Behavioral Disorder, Dementia, Ataxia, and Rigidity in a Large Family With TATA Box-Binding Protein Mutation
AbstractBACKGROUND: Spinocerebellar ataxia type 17 is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in the TATA box-binding protein gene. Ataxia is typically the first sign whereas behavioral symptoms occur later. OBJECTIVE: To characterize the unusual phenotypic expression of a large spinocerebellar ataxia type 17 kindred. DESIGN: Clinical, neuropathological, and molecular genetic characterization of a 4-generation family with 16 affected patients. RESULTS: Behavioral symptoms and frontal impairment dominated the early stages preceding ataxia, rigidity, and dystonic movements. Neuropathological examination showed cortical, subcortical, and cerebellar atrophy. Purkinje cell loss and gliosis, pseudohypertrophic degeneration of the inferior olive, marked neuronal loss and gliosis in the caudate nucleus, and in the medial thalamic nuclei were salient features together with neuronal intranuclear inclusions stained with anti-TATA box-binding protein and antipolyglutamine antibodies. The disease was caused by a stable 52 CAG repeat expansion of the TATA box-binding protein gene, although there was apparent variability in the age of onset. CONCLUSION: The characteristics of this family broaden the clinical picture of spinocerebellar ataxia type 17: initial presenile dementia with behavioral symptoms should be added to ataxia, rigidity, and dystonic movements, which are more commonly encountered.
Effects of cerebellar repetitive transcranial magnetic stimulation plus physiotherapy in spinocerebellar ataxias – A randomized clinical trial
AbstractBACKGROUND: In absence of drug therapy options, standard treatment for spinocerebellar ataxia consists of symptomatic physiotherapy and speech therapy. New therapeutic options are urgently needed. Transcranial magnetic stimulation is a promising therapeutic option, but applicability is limited by lengthy duration of stimulation protocols. METHODS: In this randomized sham controlled clinical trial, patients were assigned to verum (n = 15) or sham (n = 18) cerebellar transcranial magnetic stimulation. To yield best possible treatment effects, both intervention groups received intensified physiotherapy for the duration of the study. RESULTS: Ataxia severity was reduced by 1.6 points on the Scale for assessment and Rating of Ataxia among patients in the verum group (p < 0.001). Clinical improvement was significantly larger in the verum group, compared to the sham group (p < 0.01). The treatment effect was mainly carried by improved appendicular coordination. Patients in the verum group also significantly improved in the 8 Meter Walk Test (p < 0.05) and PATA rate (p < 0.01). CONCLUSIONS: Cerebellar rTMS ameliorates ataxia severity in patient with spinocerebellar ataxia. Condensing treatment duration to only 5 days without reduction of treatment effects facilitates applicability and therefore broadens availability to larger patient populations.
Expert Opinion on Pharmacotherapy · 2003 · 4 citations
Spinocerebellar degeneration
AbstractThe spinocerebellar degenerations/ataxias (SCAs) are a diverse group of rare, slowly progressive, neurological diseases, often inherited but of incompletely understood pathophysiology, which affect the cerebellum and its related pathways. They have few animal models and share no reliable biomarkers. They have, as yet, no universally validated rating scale for use in clinical trials. In the past 25 years, there have been, at most, 18 controlled (Class 1) trials for ataxia, which have focused on neurotransmitter mechanisms. There is currently only one National Institute of Neurological Disorders and Stroke-sponsored drug trial for ataxia (Phase I study of idebenone in Friedreich's ataxia). There are, as yet, no FDA-approved drugs for SCA. Current treatment practices encompass rehabilitation interventions and off-label use of symptomatic medications [1,2].
Revista Neurociências · 2013 · 3 citations · open access
Atendimento Fisioterapêutico para Indivíduos com Ataxia Espinocerebelar: Uma Revisão da Literatura
AbstractThe spinocerebellar ataxia (SCA) is a disorder characterized by deficits in the execution of coordinated movements with progressive postural sway associated with difficulty in maintaining balance and various other motor disorders. The gait may be ataxic, with broadening the base of support, instability, irregular steps and slow, lateropulsion and trembling in range of motion, so that physical therapy is an important alternative for the improvement of the disorders of this pathology. Objective. Make, based on scientific literature, a review of physical therapy strategies in the treatment of spinocerebellar ataxia. Method. The study researches the databases Medline and SciELO from 2001 to 2011, considering the following keywords: ataxia espinocerebelar, Fisioterapia, tratamento, reabilitação and its correlates in English. Results. We found 33 studies that had as its main theme ataxia, 20 articles were excluded because they did not report the physical therapy approach for this type of pathology. After review, 13 references were used. Conclusions. After this study, the importance of physical therapy in the treatment of patients with SCA becomes obvious, according to the benefits promoted, as all studies found an improvement of symptoms of this pathology. Methodological limitations observed suggest the need for greater rigor in future research.
AbstractNo disease-modifying therapy has been established for spinocerebellar degeneration and multiple system atrophy, and only symptomatic therapy is currently available. Taltirelin and protirelin are drugs covered by health insurance for cerebellar ataxia symptoms, and are expected to suppress the progression of symptoms. Muscle relaxants are used for spasticity associated with spinocerebellar degeneration, and vasopressors and therapeutic agents for dysuria are used for autonomic symptoms of multiple system atrophy. It is necessary to develop a new therapeutic agent with a different mechanism of action, aimed specifically at modifying the disease progression in patients with spinocerebellar degeneration and multiple system atrophy.
Expert Opinion on Pharmacotherapy · 2003 · 0 citations
Spinocerebellar degeneration
AbstractThe spinocerebellar degenerations/ataxias (SCAs) are a diverse group of rare, slowly progressive, neurological diseases, often inherited but of incompletely understood pathophysiology, which affect the cerebellum and its related pathways. They have few animal models and share no reliable biomarkers. They have, as yet, no universally validated rating scale for use in clinical trials. In the past 25 years, there have been, at most, 18 controlled (Class 1) trials for ataxia, which have focused on neurotransmitter mechanisms. There is currently only one National Institute of Neurological Disorders and Stroke-sponsored drug trial for ataxia (Phase I study of idebenone in Friedreich’s ataxia). There are, as yet, no FDA-approved drugs for SCA. Current treatment practices encompass rehabilitation interventions and off-label use of symptomatic medications [1,2].
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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