DeCure's autonomous AMR AI scientist is researching a drug-repurposing hypothesis for visceral Leishmaniasis — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleVisceral Leishmaniasis maps to a 4-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 visceral leishmaniasis 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
interleukin 10 (IL10) — IL10 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 2ILK · 1.6 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Visceral leishmaniasis treatment has advanced regionally but no universal therapy exists. In South Asia, elimination efforts have a clear strategy: single-dose liposomal amphotericin B as first-line and a combination of paromomycin and miltefosine as second-line. In Eastern Africa, the combination of sodium stibogluconate (SSG) and paromomycin improved on SSG monotherapy but requires 17 days of painful double injections and carries risk of SSG-related cardiotoxicity. Attempts to improve that combination in Eastern Africa have been unsuccessful. Pharmacokinetic studies revealed that children are underexposed to miltefosine, leading to an allometric dosing regimen.
The main limits to reducing deaths remain difficulty in field diagnosis and patients’ lack of access to treatment. No new drugs were in early development as of 2006, though by 2018 six candidates from five new chemical classes had reached phase I. Combination therapy is recommended to prevent resistance against the limited available options. Systemic toxicity, high costs, arduous regimens, and rising drug resistance are persistent barriers. Material-based platforms (nano- and microformulations) have been evaluated in preclinical models and may improve pharmacokinetics and enable patient-friendly routes of administration, but these remain at the preclinical stage.
What is still missing is funding to move nanoformulations from preclinical work into human trials, a trial design that can accommodate regional differences in drug response and resistance patterns, and better patient stratification—particularly for children, who are systematically underexposed to miltefosine. Without these, the gap between promising candidates and accessible, tolerable therapy will persist.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Recent Development of Visceral Leishmaniasis Treatments: Successes, Pitfalls, and Perspectives
AbstractResearch in visceral leishmaniasis in the last decade has been focused on how better to use the existing medicines as monotherapy or in combination. Systematic research by geographical regions has shown that a universal treatment is far from today's reality. Substantial progress has been made in the elimination of kala-azar in South Asia, with a clear strategy on first- and second-line therapy options of single-dose liposomal amphotericin B and a combination of paromomycin and miltefosine, respectively, among other interventions. In Eastern Africa, sodium stibogluconate (SSG) and paromomycin in combination offer an advantage compared to the previous SSG monotherapy, although not exempted of limitations, as this therapy requires 17 days of painful double injections and bears the risk of SSG-related cardiotoxicity. In this region, attempts to improve the combination therapy have been unsuccessful. However, pharmacokinetic studies have led to a better understanding of underlying mechanisms, like the underexposure of children to miltefosine treatment, and an improved regimen using an allometric dosage. Given this global scenario of progress and pitfalls, we here review what steps need to be taken with existing medicines and highlight the urgent need for oral drugs. Furthermore, it should be noted that six candidates belonging to five new chemical classes are reaching phase I, ensuring an optimistic near future.
Expert Review of Anti-infective Therapy · 2006 · 58 citations
Treatment options for visceral leishmaniasis
AbstractThis review summarizes the current developments in therapy for visceral leishmaniasis. With the recent introduction of new drugs, the main limits in reducing deaths from visceral leishmaniasis are difficulty in diagnosis in the field and health inequality--patients lack of access to treatment. No new drugs are currently in the early stages of development. There are good reasons for the use of combination therapy; to prevent further development of resistance against the limited therapeutic options available.
Glutamine supplementation improves the efficacy of miltefosine treatment for visceral leishmaniasis
AbstractBACKGROUND: The disturbance of host metabolic pathways by Leishmania parasites has crucial consequences for the activation status of immune cells and the outcome of infection. Glutamine has been described as an immunomodulatory amino acid, yet its role during Leishmania infection is still unknown. METHODS: We performed transcriptomics in uninfected and L. donovani-infected macrophages 6 hours post-infection. Glutamine quantification by HPLC was assessed in the supernatant of macrophages throughout the infection course. For experimental L. donovani infections, mice were infected with 1.0 x 108 stationary L. donovani promastigotes. Glutaminase (GLS) chemical inhibition was performed using BPTES and glutamine was administered throughout infection. For combined therapy experiment, a daily administration of miltefosine and glutamine was performed by oral gavage. Parasite burden was determined using a Taqman-based assay. Immune cell phenotyping and cytotoxicity were performed in splenic cells using flow cytometry. FINDINGS: We show that glutamine is essential for the control of L. donovani infection. Transcriptomic analysis of L. donovani-infected macrophages demonstrated an upregulation of genes involved in glutamine metabolism. Pharmacological inhibition of glutaminolysis significantly increased the susceptibility to infection, accompanied by an increased recruitment of anti-inflammatory myeloid cells and impaired T cell responses. Remarkably, the supplementation of glutamine to mice infected with L. donovani during miltefosine treatment potentiates parasite clearance through the development of a more effective anti-Leishmania adaptive immune response. CONCLUSIONS: Our data indicates that dietary glutamine supplementation may act as a promising adjuvant for the treatment of visceral leishmaniasis.
Nano- and Microformulations to Advance Therapies for Visceral Leishmaniasis
AbstractVisceral leishmaniasis (VL) is a deadly, vector-borne, neglected tropical disease endemic to arid parts of the world and is caused by a protozoan parasite of the genus Leishmania. Chemotherapy is the primary treatment for this systemic disease, and multiple potent therapies exist against this intracellular parasite. However, several factors, such as systemic toxicity, high costs, arduous treatment regimen, and rising drug resistance, are barriers for effective therapy against VL. Material-based platforms have the potential to revolutionize chemotherapy for leishmaniasis by imparting a better pharmacokinetic profile and creating patient-friendly routes of administration, while also lowering the risk for drug resistance. This review highlights promising drug delivery strategies and novel therapies that have been evaluated in preclinical models, demonstrating the potential to advance chemotherapy for VL.
Research progress on the diagnostic methods of visceral leishmaniasis
AbstractVisceral leishmaniasis is an important parasitosis which severely damages the health of people in the world.Rapid and accurate diagnosis is crucial in treatment and control of the disease.In this paper we reviewed the progress on the diagnostic methods of visceral leishmaniasis.
Key words:
Visceral leishmaniasis; Diagnosis; Immunology; Molecular biology
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.
