DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for trypanosomiasis — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleTrypanosomiasis maps to a 3-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 trypanosomiasis 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
ornithine decarboxylase 1 (ODC1) — ODC1 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 plpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2OO0 · 1.9 Å · ligand PYRIDOXAL-5'-PHOSPHATE (PLP). Experimental structure, not a prediction.
What the evidence adds up to
Melarsoprol remains the first-choice drug for human African trypanosomiasis, but its half-life measured by HPLC is less than one hour, compared with 35 hours by bioassay and atomic absorption spectroscopy, indicating active metabolites. One metabolite, melarsen oxide, reaches maximum plasma concentration 15 minutes after administration, has a clearance of 21.5 mL/min/kg, and a free half-life of 3.9 hours. Either melarsen oxide or another undiscovered metabolite binds irreversibly to proteins. In a rodent model of acute infection, 20 of 20 mice were cured with melarsen oxide at 0.1 to 1 mg/kg intravenously or 2.2 mg/kg intraperitoneally. In a rodent model of central nervous system infection, five of six mice survived more than 180 days at 5 mg/kg intravenously, suggesting sufficient blood-brain barrier penetration.
A 1999 review states that existing approved drugs for human African trypanosomiasis are old, toxic, and expensive, and that therapeutic failures are common. Factors contributing to chemotherapy problems include differences in disease epidemiology, difficulties in diagnosis and staging, drug availability and pharmacology, standardisation of regimens, response to therapy, follow-up periods, relapses, and clinical trials. New therapeutic approaches mentioned include development and approval of new drugs, new regimens, drug combinations, and new formulations.
A 2021 follow-up study of two imported patients with human African trypanosomiasis assessed prognosis after treatment by examining infection at 1, 3, 8, and 12 months post-treatment. Both patients recovered satisfactorily with no signs of relapse after standardised treatment.
What is still missing: the 2000 study notes that prospects for trypanosomiasis treatment are deplorable and that investigations on improving old drugs are required, but no large-scale clinical trial of melarsen oxide in humans has been reported. The 1999 review highlights the lack of standardised treatment regimens and reliable clinical trial data. The 2021 study is limited to two cases, so no generalisable conclusions about patient stratification or optimal treatment duration can be drawn. Funding for new drug development and for rigorous comparative trials of existing compounds remains absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Investigations of the metabolites of the trypanocidal drug melarsoprol
AbstractBACKGROUND: Melarsoprol remains the first-choice drug for trypanosomiasis (human African sleeping sickness). To contribute to the sparse pharmacologic data and to better understand the cause of the frequent serious adverse reactions, we investigated the metabolism of this 50-year-old organoarsenic compound. RESULTS: The half-life of melarsoprol determined by HPLC was <1 hour compared with 35 hours determined by bioassay and atomic absorption spectroscopy, indicating the existence of active metabolites. One metabolite, melarsen oxide, was identified by ultraviolet HPLC after incubation of melarsoprol with microsomes. The maximum plasma concentration of melarsenoxide was reached 15 minutes after administration; the clearance was 21.5 mL/min/kg and the half-life of free melarsen oxide was 3.9 hours. Either melarsen oxide or a yet-undiscovered active metabolite is irreversibly bound to proteins, as shown by ultrafiltration, precipitation experiments, and atomic absorption spectroscopy. Because of the poor pharmaceutical properties of melarsoprol, the therapeutic potential of melarsen oxide was investigated. In a rodent model of acute infection, 20 of 20 mice were cured (0.1 to 1 mg/kg intravenously or 2.2 mg/kg intraperitoneally). In a rodent model of central nervous system infection, five of six mice survived for more than 180 days (5 mg/kg intravenously), indicating a sufficient melarsen oxide penetration across the blood-brain barrier. CONCLUSION: The prospects for the future of trypanosomiasis treatment are deplorable. Investigations on the improvement of the use of the old drugs are therefore required. The results of this study may build a basis for further research on the cause of severe adverse reactions.
Memórias do Instituto Oswaldo Cruz · 1999 · 28 citations · open access
Therapy of Human African Trypanosomiasis: Current Situation
AbstractThis paper is a review of the current situation of the treatment of human African trypanosomiasis. The existing approved drugs are old, toxic and/or expensive. Therapeutic failures are common. Several factors may contribute to the problems of chemotherapy, including differences in the epidemiology of the disease, difficulties in the diagnosis and staging of the infection, availability, distribution and pharmacologic properties of drugs, standardization of treatment regimens, response to therapy, follow-up period, and relapses and clinical trials. The new therapeutic approaches include the development and approval of new drugs, the use of new therapeutic regimens, the study of drug combinations, and the development of new formulations.
[Follow - up prognostic study on two imported patients with human African trypanosomiasis].
AbstractOBJECTIVE: To investigate the prognosis of two rare imported patients with human African trypanosomias (HAT) after treatment in a follow-up study, and to evaluate the therapeutic efficacy, so as to provide insights into the treatment of imported HAT patients. METHODS: infection 1, 3, 8 and 12 months post-treatment to evaluate the therapeutic efficacy and prognosis. RESULTS: infection. CONCLUSIONS: Following standardized treatment, two imported cases with human African trypanosomiasis cases recover satisfactorily, without any signs of relapse.
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.
