DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for orthostatic intolerance — 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 moduleOrthostatic intolerance 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 orthostatic intolerance 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
hyperpolarization activated cyclic nucleotide gated potassium channel 4 (HCN4) — HCN4 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 pc1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6GYN · 3.4 Å · ligand 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE (PC1). Experimental structure, not a prediction.
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 · 2012 · 112 citations · open access
Deconditioning in patients with orthostatic intolerance
AbstractOBJECTIVE: To study the frequency and degree of deconditioning, clinical features, and relationship between deconditioning and autonomic parameters in patients with orthostatic intolerance. METHODS: We retrospectively studied all patients seen for orthostatic intolerance at Mayo Clinic between January 2006 and June 2011, who underwent both standardized autonomic and exercise testing. RESULTS: A total of 184 patients (84 with postural orthostatic tachycardia syndrome [POTS] and 100 without orthostatic tachycardia) fulfilled the inclusion criteria. Of these, 89% were women, and median age was 27.5 years (interquartile range [IQR] 22-37 years). Symptom duration was 4 years (IQR 2-7.8). Of the patients, 90% had deconditioning (reduced maximum oxygen uptake [VO(2max)%] <85%) during exercise. This finding was unrelated to age, gender, or duration of illness. The prevalence of deconditioning was similar between those with POTS (95%) and those with orthostatic intolerance (91%). VO(2max)% had a weak correlation with a few autonomic and laboratory parameters but adequate predictors of VO(2max)% could not be identified. CONCLUSION: Reduced VO(2max)% consistent with deconditioning is present in almost all patients with orthostatic intolerance and may play a central role in pathophysiology. This finding provides a strong rationale for retraining in the treatment of orthostatic intolerance. None of the autonomic indices are reliable predictors of deconditioning.
American Journal of Hypertension · 2000 · 0 citations · open access
A new approach in the treatment of disabling orthostatic intolerance
AbstractOrthostatic intolerance (OI) is a frequent misdiagnosis disabling condition. To evaluate the efficacy of drugs in the treatment of the autonomic/hemodynamic and clinical disturbance that characterizes OI patients. 10 women, with a mean age 31 years (21 to 57 years), with orthostatic grade by symptoms ≥ 3 (florid POTS), were evaluated before (b) and after treatment (a). Five received oral bisoprolol (B) therapy, 2 pts flurocortisone (F) and 3 pts association of B and F. The patients were study in basal and tilt position. HRV, SBPV and spontaneous baroreceptor gain were calculated by FFT and α index. The hemodynamic data was assessed by modelflow-TNO® analysis. (See Table) Units: HR in bpm; SV in ml; HRV in nu; SBPV in mmHg2; BR in ms/mmHg; TPR in dyn.s.cm-5; SBP in mmHg. Units: HR in bpm; SV in ml; HRV in nu; SBPV in mmHg2; BR in ms/mmHg; TPR in dyn.s.cm-5; SBP in mmHg. 1–Bisoprolol and/or flurocortisone improve the clinical and autonomic/hemodynamic disturbance observed in POTS. 2–All medical personnel must be alert to the diagnosis of this disabling misdiagnosis syndrome with such an easy treatment and marked clinical improvement.
Vnitřní lékařství · 2023 · 0 citations · open access
Selected biomarkers of orthostatic intolerance
AbstractOrthostatic intolerance (OI) is defined as a group of diseases which symptoms are typically manifested in a standing position. These symptoms result from cerebral hypoperfusion and disappear in the supine position. We include postural orthostatic intolerance syndrome (POTS), orthostatic hypotension (OH) and vasovagal orthostatic syncope in this group of diseases. Each of them have similar clinical presentation (blurred vision, weakness, dizziness, nausea, headaches, fatigue). However, they vary from each other in biochemical, autonomic and hemodynamic characteristics. The aim of the work is to provide an overview of humoral and non-human markers that are involved in the etiopathogenesis of orthostatic intolerance.
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.
