DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hyperhomocysteinemia — 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 moduleHyperhomocysteinemia 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 hyperhomocysteinemia 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
cystathionine beta-synthase (CBS) — CBS 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 hemdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9SQ0 · 2.74 Å · ligand PROTOPORPHYRIN IX CONTAINING FE (HEM). 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.
New England Journal of Medicine · 1991 · 2178 citations · open access
Hyperhomocysteinemia: An Independent Risk Factor for Vascular Disease
AbstractBACKGROUND: Hyperhomocysteinemia arising from impaired methionine metabolism, probably usually due to a deficiency of cystathionine beta-synthase, is associated with premature cerebral, peripheral, and possibly coronary vascular disease. Both the strength of this association and its independence of other risk factors for cardiovascular disease are uncertain. We studied the extent to which the association could be explained by heterozygous cystathionine beta-synthase deficiency. METHODS: We first established a diagnostic criterion for hyperhomocysteinemia by comparing peak serum levels of homocysteine after a standard methionine-loading test in 25 obligate heterozygotes with respect to cystathionine beta-synthase deficiency (whose children were known to be homozygous for homocystinuria due to this enzyme defect) with the levels in 27 unrelated age- and sex-matched normal subjects. A level of 24.0 mumol per liter or more was 92 percent sensitive and 100 percent specific in distinguishing the two groups. The peak serum homocysteine levels in these normal subjects were then compared with those in 123 patients whose vascular disease had been diagnosed before they were 55 years of age. RESULTS: Hyperhomocysteinemia was detected in 16 of 38 patients with cerebrovascular disease (42 percent), 7 of 25 with peripheral vascular disease (28 percent), and 18 of 60 with coronary vascular disease (30 percent), but in none of the 27 normal subjects. After adjustment for the effects of conventional risk factors, the lower 95 percent confidence limit for the odds ratio for vascular disease among the patients with hyperhomocysteinemia, as compared with the normal subjects, was 3.2. The geometric-mean peak serum homocysteine level was 1.33 times higher in the patients with vascular disease than in the normal subjects (P = 0.002). The presence of cystathionine beta-synthase deficiency was confirmed in 18 of 23 patients with vascular disease who had hyperhomocysteinemia. CONCLUSIONS: Hyperhomocysteinemia is an independent risk factor for vascular disease, including coronary disease, and in most instances is probably due to cystathionine beta-synthase deficiency.
Clinical Interventions in Aging · 2015 · 26 citations · open access
Hyperhomocysteinemia is an independent predictor of long-term clinical outcomes in Chinese octogenarians with acute coronary syndrome
AbstractOBJECTIVE: To evaluate the prognostic value of homocysteine (Hcy) in Chinese acute coronary syndrome (ACS) octogenarians. METHODS: The study cohort comprised 660 consecutive ACS octogenarians who underwent coronary angiography. We classified the patients into three groups according to Hcy tertiles. Kaplan-Meier method was performed for survival and major adverse cardiac events (MACE) rates. Multivariate Cox regression was performed to identify mortality predictors. Receiver operating characteristic curve analysis was performed to predict the cutoff value of Hcy for all-cause mortality. RESULTS: The follow-up period was 28 (inter-quartile range: 16-38) months. Diastolic blood pressure, ratios of male, renal failure and old myocardial infarction in high plasma level Hcy (H-Hcy) group were higher than those in low (L-Hcy) and middle (M-Hcy) plasma level of Hcy groups (P<0.05). The Hcy level was positively correlated with uric acid level (r=0.211, P=0.001) and Cystatin C (Cys C) level (r=0.212, P=0.001) and negatively correlated with estimated glomerular filtration rate (r=-0.148, P=0.018). For the long-term outcomes, the cumulative survival rate of H-Hcy group was significantly lower than that of L-Hcy and M-Hcy groups (P=0.006). All-cause mortality and MACE of H-Hcy group were higher than those of L-Hcy and M-Hcy group (P=0.0001, P=0.0008). Hcy is an independent predictor for long-term all-cause mortality (odds ratio =2.26, 95% CI=1.23-4.16, P=0.023) and MACE (odds ratio =1.91, 95% CI=1.03-3.51, P=0.039). Receiver operating characteristic curve analysis indicated the predictive cutoff value of Hcy for all-cause mortality was 17.67 μmol/L (0.667, 0.681). CONCLUSION: In ACS octogenarians, hyperhomocysteinemia is an important predictor for long-term all-cause mortality and MACE.
World Journal of Gastroenterology · 2011 · 15 citations · open access
Is hyperhomocysteinemia relevant in patients with celiac disease?
AbstractAIM: To investigate whether this might be related to the presence of hyperhomocysteinemia. METHODS: From January 1998 to December 2008, we evaluated the presence of hyperhomocysteinemia in a series of 165 adult celiac disease (CD) patients (138 females and 27 males, mean age 43 years). RESULTS: Hyperhomocysteinemia was evident in 32 patients (19.3%), although most of them had moderate levels (mean value 25 mcg/ml; range 15-30). Only one patient had a history of myocardial infarction (heterozygosis for N5-N10-metil tetrahydrofolate reductase mutation). CONCLUSION: The systematic assessment of hyperhomocysteinemia seems, at present, unjustified in CD patients.
Intravenous Treatment of Hyperhomocysteinemia in Patients on Chronic Hemodialysis—A Pilot Study
AbstractBACKGROUND: Treatment of hyperhomocysteinemia in patients with end-stage renal disease (ESRD) can be performed with the oral application of vitamins. However, this therapy rarely normalizes total homocysteine (tHcy) levels. Frequently, a rebound is observed after the end of treatment. Currently, no data are available about intravenous combination therapy with folic acid, pyridoxine (B6), and cyanocobalamin (B12). METHODS: We conducted a prospective pilot study comprising 13 patients on chronic hemodialysis treatment (63.7+/-4.9 years; 6 female, 7 male) for 27 weeks. The patients received 10 mg folic acid and 100 mg pyridoxine intravenously (IV) after each dialysis plus 1000 microg vitamin B12 IV once a week for 9 weeks. Between weeks 10 and 18 the patients received 10 mg folic acid, 100 mg vitamin B6 once a week, and 1000 microg vitamin B12 bimonthly IV. RESULTS: The therapy regimen decreased tHcy concentration (baseline: 30.5+/-2.2 micromol/L) significantly to 17.4+/-1.2 micromol/L, 15.6+/-1.0 micromol/L, and 16.4+/-0.1 micromol/L after 3, 6, and 9 weeks, respectively (p<0.01 vs. baseline concentration). The maximum reduction (-47.5+/-3.3%) of tHcy concentration was measured after 6 weeks of therapy. During the following maintenance therapy, tHcy-levels did not increase and no rebound of tHcy was detected during follow-up (week 27:16.5+/-1.97 micromol/L). CONCLUSION: The concept of a short, high-dose induction therapy with intravenous folic acid, pyridoxine, cyanocobalamin, and a subsequent low-dose maintenance regimen is effective in the treatment of hyperhomocysteinemia in patients with ESRD.
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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