DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for orthostatic hypotension 1 — 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 moduleOrthostatic hypotension 1 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 orthostatic hypotension 1 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
dopamine beta-hydroxylase (DBH) — DBH 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 4ZEL · 2.9 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a study of 571 elderly patients (mean age 83.7) attending a comprehensive geriatric assessment unit, 32.1% were diagnosed with orthostatic hypotension. The risk increased with the total number of drugs taken (odds ratio 1.09 per additional drug) and more strongly with the number of drugs known to cause orthostatic hypotension (odds ratio 1.22 per additional drug). Specific drug classes that raised risk after adjustment were alpha-blockers (odds ratio 1.82), calcium channel blockers (odds ratio 1.66), selective serotonin reuptake inhibitors (odds ratio 2.09), and tricyclic antidepressants (odds ratio 4.36). No association was found between orthostatic hypotension and age, cognitive or functional status, or comorbidity index.
A separate genetic study of 415 community-dwelling individuals aged 50 or older (mean age 70.5) found no link between orthostatic hypotension and polymorphisms in the renin-angiotensin system (angiotensin-converting enzyme I/D, angiotensinogen M235T, angiotensin II type 1 receptor A1166C). However, polymorphisms in genes encoding sympathetic nervous system components were associated with blood pressure change on standing. The GNAS1 CC genotype carried an odds ratio of 2.79 for orthostatic hypotension, and the GNB3 C allele an odds ratio of 1.78.
Two case reports from 2019 describe drug-related orthostatic hypotension managed differently in similar presentations, highlighting the lack of consistent guidelines. A 1996 review notes that evidence for efficacy of drugs used to treat orthostatic hypotension is limited and that the pathophysiological mechanisms are heterogeneous. A 1991 paper emphasises that the combination of debility, medications, and common geriatric illnesses such as diabetes creates symptoms, and recommends careful positional blood pressure measurement as routine nursing practice.
What remains missing is a large, randomised trial that stratifies patients by the specific drugs they are taking and by genetic markers of sympathetic nervous system function. Without such a trial, the relative contributions of medication withdrawal versus pharmacological treatment cannot be disentangled, and no drug can be recommended for routine use in orthostatic hypotension.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Hypertension · 2015 · 63 citations
Orthostatic hypotension and drug therapy in patients at an outpatient comprehensive geriatric assessment unit
AbstractOBJECTIVE: To assess the rate of orthostatic hypotension and factors associated with it among elderly patients who underwent a comprehensive, ambulatory geriatric assessment. METHODS: The study included patients 65 years and older who were assessed in the outpatient comprehensive geriatric assessment unit. Data were collected from the computerized medical record including sociodemographic data, lifestyle, falls, blood pressure, BMI, functional and cognitive status, medications, and comorbidity. RESULTS: The study population consisted of 571 patients who underwent assessment over a nine-year period. The mean age was 83.7 ± 6.1, 35.9% were men, and 183 (32.1%) were diagnosed with orthostatic hypotension. Multiple drugs, in general, and multiple drugs with the potential to cause orthostatic hypotension in particular increased the risk for orthostatic hypotension after adjustment for age, sex, chronic comorbidity, and supine systolic blood pressure ≥150 mmHg [odds ratio (OR) = 1.09, 95% confidence interval (CI): 1.03-1.14 and OR = 1.22, 95% CI: 1.08-1.37, respectively]. In addition, α-blockers and calcium channel blockers increased the risk for orthostatic hypotension after similar adjustments (OR = 1.82, 95% CI: 1.01-3.16 and OR = 1.66, 95% CI: 1.11-2.48, respectively). Similarly, two additional drug types increased the risk for orthostatic hypotension: selective serotonin reuptake inhibitors (OR = 2.09, 95% CI: 1.33-3.19) and tricyclic antidepressants (OR = 4.36, 95% CI: 1.85-10.06). There were no specific associations between age, cognitive and functional state, morbidity (as measured by the Charlson Comorbidity Index), and specific diseases, and orthostatic hypotension. CONCLUSION: The results of the present study reinforce evidence of an association between drug therapy and orthostatic hypotension.
Polymorphisms of genes encoding components of the sympathetic nervous system but not the renin–angiotensin system as risk factors for orthostatic hypotension
AbstractOBJECTIVE: The genetic background of orthostatic hypotension, an important risk factor for future cardiovascular morbidity and mortality, was investigated. DESIGN AND METHODS: The study subjects comprised 415 community-dwelling individuals, who were free from any cardiovascular complications, aged 50 years or older (mean age 70.5 +/- 9 years). Basal systolic blood pressure (SBP) was measured twice in supine posture after resting for more than 10 min. The orthostatic change in SBP was determined at 1 min and 3 min after standing up. The maximum change in SBP after standing was determined. Orthostatic hypotension was defined as a decline in SBP greater than 20 mmHg. The polymorphisms of genes encoding components of the renin-angiotensin system and sympathetic nervous system, which play pivotal roles in postural change in blood pressure regulation, were determined. RESULTS: There were no significant associations between the maximum change in SBP, the prevalence of orthostatic hypotension and gene polymorphisms of angiotensin-converting enzyme I/D, angiotensinogen M235T and angiotensin II type 1 receptor A1166C. On the contrary, polymorphism of the Gs protein alpha-subunit (GNAS1) T131C was significantly associated with the maximum change in SBP after standing [1.9 +/- 16 versus -3.6 +/- 16 mmHg (TT + TC versus CC), P = 0.008]. The prevalence of orthostatic hypotension was significantly different among GNAS1 genotypes (chi squared = 10.12, P = 0.011) and G-protein beta 3 subunit (GNB3) genotypes (chi squared = 6.12, P = 0.020). Multiple logistic regression analysis showed that both GNAS1 CC genotype [odds ratio (OR) = 2.79, 95% confidence interval (CI) 1.35-5.79, P = 0.006] and GNB3 C allele (OR = 1.78, 95% CI 1.06-3.00, P = 0.030) were independent risks for orthostatic hypotension. CONCLUSIONS: These findings indicate that genes encoding sympathetic nervous components could be involved in the predisposition for orthostatic hypotension.
Fundamental and Clinical Pharmacology · 1996 · 14 citations
Which drug for which orthostatic hypotension?
AbstractThis review focuses on the actual limits of the clinical pharmacology of drugs used for the treatment of orthostatic hypotension. The evidences for heterogeneity of the pathophysiological mechanisms of primary orthostatic hypotension and autonomic failure are discussed. The available data on the efficacy of some drugs used in orthostatic hypotension are also discussed.
Journal of Gerontological Nursing · 1991 · 5 citations
The Prevalence of Orthostatic Hypotension in high-risk ambulatory elders
Abstract1. Orthostatic hypotension may be a serious threat, especially among the elderly. It may be characterized as a change in diastolic or systolic blood pressure, a narrowing of pulse pressure, or tachycardia. 2. Physiological changes of aging super-imposed on illness or the use of medications appear to contribute to the prevalence of orthostatic hypotension and its symptoms. It is the combination of known risk factors of debility, medications, and common geriatric illnesses, such as diabetes, that notably create the symptoms. 3. Nurses can do much to reduce the associated symptoms and threat of synergistic effects on blood pressure. Careful measurements of blood pressure and pulse in various positions should be incorporated into routine nursing practice. Management of patients with orthostatic hypotension necessitates that nursing interventions be aimed at preventing injuries from associated falls.
International Journal of Human and Health Sciences (IJHHS) · 2019 · 1 citations · open access
Drug-related Postural Hypotension: to Withdraw or Not to Withdraw (A Case Series)
AbstractOrthostatic hypotension is a common presentation in the primary care setting. Concise management is important as it can lead to falls, particularly in the elderly and can lead to significant morbidity and mortality. Its management presents as a challenge as there are differing guidelines on managing these patients. This case report illustrates two cases of drug-related orthostatic hypotension with similar presentation, however both were managed differently.International Journal of Human and Health Sciences Vol. 03 No. 04 October’19 Page : 241-244
Greater South Information System · 2019 · 0 citations · open access
Drug-related Postural Hypotension: to Withdraw or Not to Withdraw (A Case Series)
AbstractOrthostatic hypotension is a common presentation in the primary care setting. Concise management is important as it can lead to falls, particularly in the elderly and can lead to significant morbidity and mortality. Its management presents as a challenge as there are differing guidelines on managing these patients. This case report illustrates two cases of drug-related orthostatic hypotension with similar presentation, however both were managed differently.International Journal of Human and Health Sciences Vol. 03 No. 04 October'19 Page : 241-244
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.
