DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for chorea — screening already-approved drugs against its 10-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleChorea maps to a 10-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 chorea 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
calcium/calmodulin dependent protein kinase IV (CAMK4) — CAMK4 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 aminosulfonyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2W4O · 2.17 Å · ligand 5-AMINO-3-{[4-(AMINOSULFONYL)PHENYL]AMINO}-N-(2,6-DIFLUOROPHENYL)-1H-1,2,4-TRIAZOLE-1-CARBOTHIOAMIDE (DKI). Experimental structure, not a prediction.
What the evidence adds up to
In a 1990 study of 15 children with Sydenham's chorea, sodium valproate at 15 to 20 mg/kg/day led to disappearance of choreiform movements within one week in 13 children. Two children had an incomplete response, and two patients relapsed, one of whom responded when valproate was reintroduced. Mean treatment duration was 6.7 weeks, and no major side effects were observed.
A 2024 meta-analysis of 1479 Sydenham chorea patients (1325 from 1945 onward, median age 10, 68.8% female) found that immunotherapy was associated with shorter chorea duration (hazard ratio for resolution 1.51, 95% CI 1.05–2.19). Median chorea duration was 1.2 months (95% CI 1.2–2.0) for patients receiving corticosteroids for one month or more, versus 2.8 months (95% CI 2.0–3.0) for those receiving none. Factors associated with a monophasic disease course (no relapse after 24 months) were antibiotics (odds ratio for relapse 0.28, 95% CI 0.09–0.85), corticosteroids (OR 0.32, 95% CI 0.15–0.67), and sodium valproate (OR 0.33, 95% CI 0.15–0.71). At least one month of corticosteroids gave an odds ratio for relapse of 0.10 (95% CI 0.04–0.25). No treatment factor was associated with good functional outcome.
For Huntington disease chorea, a 2018 retrospective chart review of 512 patients found that 26.4% never initiated tetrabenazine, the then sole FDA-approved treatment. Most patients (66.5%) received a dose of 50 mg or less. The most common reasons for stopping upward titration were optimal chorea control (55.5%), intolerability at higher doses (31.2%), and reaching maximum recommended dose despite suboptimal control (11.4%). Chorea severity and non-persistence to tetrabenazine were associated with increased emergency visits, hospitalisations, and days hospitalised.
A 2016 review notes that new genetic and autoimmune causes of chorea continue to be identified, and that deep brain stimulation can be useful in patients who do not respond to oral medications, whether from neurodegenerative or non-degenerative causes. A 1994 review states that most late-onset chorea is either non-limiting, remits spontaneously, or responds to medication, but a minority is medically refractory or a manifestation of an untreatable disorder. What remains missing are prospective, randomised controlled trials that stratify patients by aetiology and chorea severity, and that measure functional outcomes over years, not weeks. Funding for such trials, particularly for rare chorea subtypes, is lacking.
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 · 1990 · 83 citations
Effectiveness of sodium valproate in the treatment of Sydenham's chorea
AbstractWe treated 15 children with Sydenham's chorea with sodium valproate at a dose of 15 to 20 mg/kg/d. In 13 of them the chorieform movements disappeared within 1 week of therapy. The remaining 2 had incomplete response. Two patients relapsed; 1 of them responded to the reintroduction of valproate. The mean duration of treatment was 6.7 weeks. We observed no major side effects. This study strongly suggests that valproate is an effective drug in the treatment of Sydenham's chorea.
JAMA Network Open · 2024 · 18 citations · open access
Treatments and Outcomes Among Patients with Sydenham Chorea
AbstractImportance: Sydenham chorea is the most common acquired chorea of childhood worldwide; however, treatment is limited by a lack of high-quality evidence. Objectives: To evaluate historical changes in the clinical characteristics of Sydenham chorea and identify clinical and treatment factors at disease onset associated with chorea duration, relapsing disease course, and functional outcome. Data Sources: The systematic search for this meta-analysis was conducted in PubMed, Embase, CINAHL, Cochrane Library, and LILACS databases and registers of clinical trials from inception to November 1, 2022 (search terms: [Sydenham OR Sydenham's OR rheumatic OR minor] AND chorea). Study Selection: Published articles that included patients with a final diagnosis of Sydenham chorea (in selected languages). Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Individual patient data on clinical characteristics, treatments, chorea duration, relapse, and final outcome were extracted. Data from patients in the modern era (1945 through 2022) were entered into multivariable models and stratified by corticosteroid duration for survival analysis of chorea duration. Main Outcomes and Measures: The planned study outcomes were chorea duration at onset, monophasic course (absence of relapse after ≥24 months), and functional outcome (poor: modified Rankin Scale score 2-6 or persisting chorea, psychiatric, or behavioral symptoms at final follow-up after ≥6 months; good: modified Rankin Scale score 0-1 and no chorea, psychiatric, or behavioral symptoms at final follow-up). Results: In total, 1479 patients were included (from 307 articles), 1325 since 1945 (median [IQR] age at onset, 10 [8-13] years; 875 of 1272 female [68.8%]). Immunotherapy was associated with shorter chorea duration (hazard ratio for chorea resolution, 1.51 [95% CI, 1.05-2.19]; P = .03). The median chorea duration in patients receiving 1 or more months of corticosteroids was 1.2 months (95% CI, 1.2-2.0) vs 2.8 months (95% CI, 2.0-3.0) for patients receiving none (P = .004). Treatment factors associated with monophasic disease course were antibiotics (odds ratio [OR] for relapse, 0.28 [95% CI, 0.09-0.85]; P = .02), corticosteroids (OR, 0.32 [95% CI, 0.15-0.67]; P = .003), and sodium valproate (OR, 0.33 [95% CI, 0.15-0.71]; P = .004). Patients receiving at least 1 month of corticosteroids had significantly lower odds of relapsing course (OR, 0.10 [95% CI, 0.04-0.25]; P < .001). No treatment factor was associated with good functional outcome. Conclusions and Relevance: In this meta-analysis of treatments and outcomes in patients with Sydenham chorea, immunotherapy, in particular corticosteroid treatment, was associated with faster resolution of chorea. Antibiotics, corticosteroids and sodium valproate were associated with a monophasic disease course. This synthesis of retrospective data should support the development of evidence-based treatment guidelines for patients with Sydenham chorea.
Neurology Clinical Practice · 2016 · 13 citations · open access
The non–Huntington disease choreas
AbstractPURPOSE OF REVIEW: Chorea can be due to a wide variety of causes. In this review, I provide updates on several recently identified genetic and autoimmune causes of chorea, and review evidence supporting the use of deep brain stimulation in chorea. RECENT FINDINGS: (in addition to amyotrophic lateral sclerosis and frontotemporal dementia), and those responsible for the neurodegeneration with brain iron accumulation disorders. Novel autoantibodies are increasingly being identified as associated with a variety of neurologic syndromes, including chorea, in both paraneoplastic and non-paraneoplastic settings. Deep brain stimulation can be a useful intervention in patients with chorea who do not respond to oral medications, whether due to neurodegenerative or nondegenerative causes. SUMMARY: New causes of chorea continue to be identified. Correct diagnosis is essential for prognostication and treatment.
Journal of Huntington s Disease · 2018 · 8 citations
Tetrabenazine Treatment Patterns and Outcomes for Chorea Associated with Huntington Disease: A Retrospective Chart Review
AbstractBACKGROUND: Huntington disease (HD) is a neurodegenerative disorder characterized by motor impairments (including chorea), along with behavioral, psychiatric, and cognitive symptoms. Tetrabenazine was the first US Food and Drug Administration (FDA)-approved treatment for chorea related to HD. OBJECTIVE: To examine pharmacologic treatment patterns among patients using tetrabenazine, including reasons for treatment initiation, non-initiation, dose adjustments, and discontinuation, and to quantify the burden of chorea based on healthcare resource utilization. METHODS: In this retrospective patient chart review, neurologists were recruited from the Medefield (http://www.medefield.com) opt-in panel, and selected ≤5 medical charts based on the criteria provided and abstracted data on demographics, disease history, healthcare resource use, and treatment patterns. RESULTS: 138 neurologists participated and 512 HD patient charts were reviewed. Among these patients, 26.4% did not initiate tetrabenazine. Most HD patients (66.5%) received a tetrabenazine dose ≤50 mg. The most common reasons for stopping upward titration were optimal chorea control (55.5%), intolerability of higher doses (31.2%), and reaching the maximum recommended dosage despite suboptimal chorea control (11.4%). Chorea severity and non-persistence to tetrabenazine were associated with increased emergency room visits, hospitalizations, and days hospitalized. CONCLUSIONS: Although tetrabenazine was the sole FDA-approved treatment for HD chorea until April 2017, more than one-quarter of respondents never initiated therapy. Tetrabenazine dosing was lower than predicted, and many patients experienced adverse symptoms of intolerability at high doses. New safer and more tolerable treatment options, such as deutetrabenazine, may improve treatment outcomes and reduce healthcare resource use.
Archives of Disease in Childhood · 1930 · 5 citations · open access
The Nirvanol Treatment of Chorea
AbstractVarious methods and drugs have been used in the treatment of chorea minor in children; among them are sodium salicylate, liquor arsenicalis, arsphenamine, bromides, milk injections, magnesium sulphate, thvroid extract, luminal, chloretone, and adrenalin subcarbonate. Medical literature reveals a percentage of good results from each of them, but since chorea is a more or less self-limited disease, a certain amount of scepticism accompanies any claim of cure.
Journal of accountancy online/Journal of accountancy · 1994 · 0 citations
Computer Backups Checklist
AbstractThe differential diagnosis, diagnostic evaluation, and treatment of late-onset chorea are reviewed. Late-onset chorea is rare and has a heterogeneous causation. A systematic approach to geriatric chorea greatly enhances a correct diagnosis. An accurate diagnosis is important because many causes of chorea are treatable or or, when heritable, may have significant implications for subsequent generations. Most late-onset chorea is either nonlimiting, requiring no treatment, has a spontaneous remission, or responds to medication. In a minority of patients, chorea is medically refractory or manifestation of an untreatable disorder.
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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