DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for bipolar II disorder — screening already-approved drugs against its 8-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBipolar II disorder maps to a 8-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 bipolar ii disorder 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 receptor D2 (DRD2) — DRD2 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 8alphadrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9BS9 · 2.28 Å · ligand (8alpha)-N,N-diethyl-6-methyl-9,10-didehydroergoline-8-carboxamide (7LD). Experimental structure, not a prediction.
What the evidence adds up to
The 1994 study examined linkage between bipolar illness and several candidate genes on chromosome 11—tyrosine hydroxylase, D4 dopamine receptor, tyrosinase, D2 dopamine receptor, c-Harvey-ras oncogene, and insulin gene—in 14 families of probands with bipolar illness. Two-point linkage analysis excluded close linkage to each candidate gene, and multipoint analysis of HRAS and INS excluded the 11p15 region containing DRD4 and TH. Affected-sib-pair analysis showed no preferential sharing of marker alleles at any candidate gene. The authors concluded that these negative results, obtained under different genetic models, exclude a frequent role for DRD4, TH, TYR, and DRD2 in the pathogenesis of bipolar illness.
A 1995 paper on southern leaf blight of maize reported that resistance to the fungus Bipolaris maydis is controlled by a single recessive gene, rhm, with the dominant allele Rhm conferring susceptibility. Mutation rates of Rhm to rhm were usually around 10⁻⁵, but hybrid populations between two different Rhm lines yielded approximately 15% mutants. The authors proposed a hypothesis of two linked recessive genes controlling resistance, with the unexpected mutants arising from crossovers between dominant alleles at two linked loci in repulsion phase. This two-gene model was being tested at the time of publication.
A 2010 review of remission and recovery in bipolar disorder noted that pharmacotherapy is the primary treatment and several medications have proven efficacy, but an efficacy/effectiveness gap exists in preventing recurrence of mood episodes and returning patients to full functional recovery. The review identified lack of treatment adherence as a major factor in treatment refractoriness and suggested that psychoeducation may help improve adherence and address complicating factors such as comorbidity, substance use, and cognitive impairment.
What remains missing for bipolar II disorder specifically is any direct evidence from these abstracts: no trial has tested a repurposed drug in bipolar II patients, no biomarker has been validated to stratify patients, and no funding has been committed to a dedicated repurposing study. The 1994 genetic findings rule out a frequent role for several dopamine-related genes but do not identify any actionable target. The 2010 review highlights adherence and functional recovery as unresolved problems but offers no new pharmacological strategy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Psychiatry · 1994 · 60 citations · open access
Nonlinkage of bipolar illness to tyrosine hydroxylase, tyrosinase, and D2 and D4 dopamine receptor genes on chromosome 11
AbstractOBJECTIVE: Previous linkage and allelic association studies using DNA polymorphisms, cosegregation of cytogenetic abnormalities with psychiatric illness, and assignment of genes involved in neutotransmitter metabolism suggested that chromosome 11 may harbor a gene predisposing to bipolar illness. The authors examined linkage in the families of 14 probands with bipolar illness, with the candidate genes tyrosine hydroxylase (TH), D4 dopamine receptor (DRD4) at 11p15, tyrosinase (TYR) at 11q14-q21, and D2 dopamine receptor (DRD2) at 11q22-q23, as well as with the c-Harvey-ras oncogene (HRAS) and insulin gene (INS), both located at 11p15, a region that previously showed linkage to bipolar illness. METHOD: The genetic data were analyzed with both lod score analysis (parametric) and affected-sib-pair analysis (nonparametric); both narrow and broad definitions of the clinical phenotype were used. Further influences of diagnostic uncertainties were accounted for by using diagnostic probability classes weighing the stability of each phenotype. RESULTS: Two-point linkage results excluded close linkage of bipolar illness to each candidate gene; negative results were also obtained when the narrow definition of the clinical phenotype was used. Moreover, multipoint linkage analysis of HRAS and INS excluded the 11p15 region encompassing both DRD4 and TH. In agreement with the negative linkage results, affected-sib-pair analysis did not show preferential sharing of marker alleles at any of the candidate genes. CONCLUSIONS: The negative results obtained under different genetic models exclude a frequent role for DRD4, TH, TYR, and DRD2 in the pathogenesis of bipolar illness.
Genetic Control of Resistance to Bipolaris maydis: One Gene or Two Genes?
AbstractBipolaris (Helminthosporium) maydis is the causal fungus of southern leaf blight of maize. Resistance to this disease has been determined to be controlled by a single recessive gene, designated rhm. The dominant allele, Rhm, confers susceptibility to the fungus. In our project to tag the rhm gene with transposable elements, Rhm/Rhm EIEI (EI, element) lines were crossed to an rhm tester. Screening for mutation to rhm was then conducted on the F1, Rhm/rhm EI, seedlings. Element insertions into Rhm are expected to be random events, and will mutate Rhm phenotypically to rhm (susceptible to resistant). In these tests mutation rates of Rhm to rhm were usually in the order of 10−5. However, hybrid populations between two different Rhm EI lines (Cy line and T line) yielded ˜15% mutants. To account for the unexpectedly high mutation rate, a hypothesis is proposed that there are two linked recessive genes controlling resistance. The two lines combined different in genotypic content and the unexpected 5% mutants arose from crossovers between the two dominant alleles at the two linked loci in repulsion phase (Rhm1 rhm2/rhm 1 Rhm2). It is also postulated that one of the two genes is a copy of the other created by duplication. The dominant status at either locus makes a functional product and thus abolishes resistance. The two-gene model is currently being tested. The significance and implications of this finding are discussed.
The Journal of Clinical Psychiatry · 2010 · 11 citations
Achieving Remission and Recovery in Bipolar Disorder
AbstractPharmacotherapy is the primary treatment for bipolar disorder, and several medications have proven efficacy for treating patients with the disorder. However, an efficacy/effectiveness gap exists in preventing recurrence of mood episodes and in returning patients to full functional recovery. A lack of treatment adherence is a major factor in treatment refractoriness in patients with bipolar disorder. Evidence suggests that psychoeducation can be a helpful tool in improving treatment adherence and in addressing other factors that complicate the treatment of bipolar disorder, such as comorbidity, substance use, and cognitive impairment.
AbstractAugmentation strategy is an option for patients who do not respond to one or two adequate trials of antidepressant therapy and are considered treatment-resistant. A number of drugs have been proposed for this indication, including lamotrigine, an anticonvulsant that is also licensed for the treatment of bipolar I disorder. Three retrospective chart reviews provided preliminary evidence of efficacy. However, other studies have been very small open-label studies, with the exception of one randomized, double-blind study. Although these studies indicate that lamotrigine may be effective as augmentation therapy in treatment-resistant depression, larger controlled studies are required to confirm these initial findings and to provide evidence for its use in this indication.
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.
