DeCure's autonomous AMR AI scientist is researching a drug-repurposing hypothesis for Leishmaniasis — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLeishmaniasis maps to a 6-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 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
matrix metallopeptidase 7 (MMP7) — MMP7 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 2sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2Y6D · 1.6 Å · ligand N-[(2S)-1-[4-(5-BROMOPYRIDIN-2-YL)PIPERAZIN-1-YL]SULFONYL-5-PYRIMIDIN-2-YL-PENTAN-2-YL]-N-HYDROXY-METHANAMIDE (TQJ). Experimental structure, not a prediction.
What the evidence adds up to
Leishmaniasis in the Middle East and North Africa involves four transmission cycles: zoonotic cutaneous leishmaniasis caused by Leishmania major, zoonotic visceral leishmaniasis caused by L. infantum, anthroponotic cutaneous leishmaniasis caused by L. tropica, and anthroponotic visceral leishmaniasis caused by L. donovani. A 2021 review notes that shared expressed proteins between Leishmania parasites and cancer cells, related to survival, development, and pathogenicity, are scarce but might offer future therapeutic targets. A 2008 genomic study in mice found that introducing the L. donovani gene Li1040 into L. major increased visceral infection in BALB/c mice, suggesting that sequence variations in shared genes can influence virulence and tissue tropism.
A 2009 opinion piece argues that combining immunotherapy with chemotherapy could rapidly induce an effector immune response, potentially reducing drug toxicity and resistance compared to long-term monotherapy, but states that a safe, potent drug and an affordable therapeutic vaccine remain to be developed. A 2014 study in 27 C57Bl/6 mice infected with L. amazonensis found that the combination of miltefosine (200 mg/kg/day) and pentoxifylline (8 mg/kg/day) significantly reduced the number of viable Leishmania compared to miltefosine alone or no treatment (p < 0.05), measured by paw diameter and parasitological criteria.
A 2024 study formulated fluconazole nano-emulsions (FLZ-NEs) with 2 % oleic acid, 20 % Tween 20, and 10 % ethyl alcohol, achieving a droplet size of 10.51 ± 0.24 nm and zeta potential of -0.41 ± 0.17 mV. In vitro, FLZ-NEs showed a threefold increase in activity against promastigotes and a thirtyfold increase against amastigotes compared to fluconazole alone, with a ninefold improvement in targeting parasites within infected macrophages. In mice, FLZ-NE treatment led to decreased disease severity, weight growth, and quicker ulcer healing, with reduced tissue damage on histopathology. The 2008 and 2014 studies used mouse models only; the 2024 nano-emulsion data are from in vitro and mouse experiments. No human trial data are reported in these abstracts. What is still missing is clinical testing in humans, a proven therapeutic vaccine for immunotherapy, and patient stratification by Leishmania species and immune status.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
African Health Sciences · 2019 · 106 citations · open access
Review of Leishmaniasis in the Middle East and North Africa
AbstractBackground: Cutaneous and visceral forms of leishmaniasis are the most important protozoan infection in the Middle East and North Africa (MENA).Objectives: Review the current knowledge on leishmaniasis in the MENA.Methods: The data presented in this review are gathered primarily from WHO reports and from an extensive literature search on PubMed.Results: There are four cycles of transmission of leishmaniasis: zoonotic cutaneous leishmaniasis (ZCL), induce by Leishmania (L.) major, transmitted by Phlebotomus (P.) papatasi, with rodent species of Psammomys obesus, Meriones libycus, Nesokia indica, and Rhombomys opimus are considered as host reservoirs. Zoonotic visceral leishmaniasis (ZVL) is inducing by L. infantum, transmitted by several Phlebotomus spp. of the sub-genus Larroussius and mainly P. perniciosus in more than one-half of the MENA countries and the dog species of Canis familiaris are considered as the main reservoirs. Anthroponotic cutaneous leishmaniasis (ACL), induce by L. tropica and transmitted by P. sergenti, without any non-human reservoir in most cases. Anthroponotic visceral leish- maniasis (AVL) induces by L. donovani spreads through P. alexandri, circulates exclusively in humans.Conclusion: There are many challenges facing the successful control of leishmaniasis. However, there is continuing research into the treatment of leishmaniasis and potentially vaccinations for the disease.Keywords: Cutaneous and visceral leishmaniasis, global distribution, Middle East and North Africa.
Transactions of the Royal Society of Tropical Medicine and Hygiene · 2009 · 45 citations · open access
Immunological stimulation for the treatment of leishmaniasis: a modality worthy of serious consideration
AbstractInstead of relying on drugs to reduce the parasite burden of leishmaniasis, and waiting for the effector immune response to develop in time to control the parasites, immunotherapy in conjunction with chemotherapy can rapidly induce the effector immune response. With a safe and potent drug plus an affordable therapeutic vaccine (immunostimulant), which remains to be developed, a single visit by patients with visceral or cutaneous leishmaniasis might be sufficient to induce a quick and lasting recovery. Drug toxicity and the emergence of resistance could also be dramatically reduced compared with present long-term monotherapy. Immunotherapy could be an effective addition to chemotherapy for leishmaniasis.
Potential therapeutic targets shared between leishmaniasis and cancer
AbstractThe association of leishmaniasis and malignancies in human and animal models has been highlighted in recent years. The misdiagnosis of coexistence of leishmaniasis and cancer and the use of common drugs in the treatment of such diseases prompt us to further survey the molecular biology of Leishmania parasites and cancer cells. The information regarding common expressed proteins, as possible therapeutic targets, in Leishmania parasites and cancer cells is scarce. Therefore, the current study reviews proteins, and investigates the regulation and functions of several key proteins in Leishmania parasites and cancer cells. The up- and down-regulations of such proteins were mostly related to survival, development, pathogenicity, metabolic pathways and vital signalling in Leishmania parasites and cancer cells. The presence of common expressed proteins in Leishmania parasites and cancer cells reveals valuable information regarding the possible shared mechanisms of pathogenicity and opportunities for therapeutic targeting in leishmaniasis and cancers in the future.
A Genomic-Based Approach Combining In Vivo Selection in Mice to Identify a Novel Virulence Gene in Leishmania
AbstractBACKGROUND: Infection with Leishmania results in a broad spectrum of pathologies where L. infantum and L. donovani cause fatal visceral leishmaniasis and L. major causes destructive cutaneous lesions. The identification and characterization of Leishmania virulence genes may define the genetic basis for these different pathologies. METHODS AND FINDINGS: Comparison of the recently completed L. major and L. infantum genomes revealed a relatively small number of genes that are absent or present as pseudogenes in L. major and potentially encode proteins in L. infantum. To investigate the potential role of genetic differences between species in visceral infection, seven genes initially classified as absent in L. major but present in L. infantum were cloned from the closely related L. donovani genome and introduced into L. major. The transgenic L. major expressing the L. donovani genes were then introduced into BALB/c mice to select for parasites with increased virulence in the spleen to determine whether any of the L. donovani genes increased visceral infection levels. During the course of these experiments, one of the selected genes (LinJ32_V3.1040 (Li1040)) was reclassified as also present in the L. major genome. Interestingly, only the Li1040 gene significantly increased visceral infection in the L. major transfectants. The Li1040 gene encodes a protein containing a putative component of an endosomal protein sorting complex involved with protein transport. CONCLUSIONS: These observations demonstrate that the levels of expression and sequence variations in genes ubiquitously shared between Leishmania species have the potential to significantly influence virulence and tissue tropism.
Enhancing the efficacy of fluconazole against Leishmania major: Formulation and evaluation of FLZ-nanoemulsions for topical delivery
AbstractBACKGROUND: Cutaneous Leishmaniasis (CL) remains a significant public health concern, particularly in the tropical and subtropical regions. Present treatment options for CL such as Fluconazole (FLZ) face limitations, including low solubility and bioavailability. This study aimed to address these challenges by investigating the use of nano-emulsions (NEs) to enhance the efficacy of FLZ against Leishmania major(L.major). MATERIALS AND METHODS: FLZ-NEs were formulated with oleic acid, Tween-20, and ethanol using low-energy emulsification at various surfactant/co-surfactant ratios. Subsequently, a comprehensive analysis was conducted to assess the physicochemical characteristics of the samples. This analysis encompassed stability, zeta potential, pH, viscosity, refractive index, and droplet size. We then studied the anti-parasitic properties of these optimized FLZ-NEs both in vitro and in vivo. RESULTS: The selected nano-emulsion (NE) formulation (2 % oleic acid, 20 % Tween 20, 10 % ethyl alcohol) showcased desirable properties like small droplet size (10.51 ± 0.24 nm), low dispersity (0.19 ± 0.03), and zeta potential value (- 0.41 ± 0.17 mV), key for stability and targeted drug delivery. This optimal formulation translated into remarkable efficacy. In vitro, FLZ-NEs demonstrated a threefold increase in their ability to combat promastigotes and a remarkable thirtyfold increase in their ability to combat amastigotes. Additionally, they demonstrated a ninefold advantage in their ability to specifically target parasites within infected macrophages, thereby attacking the infection site. These promising in vitro results translated into improved outcomes in vivo. Compared to other chemicals studied, FLZ-NE-treated mice showed decreased disease severity, weight growth, and quicker ulcer healing. It was further supported by histopathological research, which showed reduced tissue damage linked to Leishmania infection. CONCLUSION: These findings show the potential of nanotechnology-based drug delivery in improving anti-leishmanial treatment.
Revista da Sociedade Brasileira de Medicina Tropical · 2014 · 9 citations · open access
Effectiveness of miltefosine-pentoxifylline compared to miltefosine in the treatment of cutaneous leishmaniasis in C57Bl/6 mice
AbstractINTRODUCTION: The treatment of leishmaniasis ischallenging, given the difficulties in drug administration and resistance. Therefore, we chose to test the efficacy of miltefosine combined with pentoxifylline. METHODS: Twenty-seven isogenic C57Bl/6 mice were infected with Leishmania (Leishmania) amazonensis, and equally divided into three groups: miltefosine (200mg/kg/day), miltefosine (200mg/kg/day) with pentoxifylline (8mg/kg/day), and untreated. Response to treatment was evaluated using paw diameter and parasitological criteria. RESULTS: The number of viable Leishmania reduced significantly within the miltefosine-pentoxifylline group (p < 0.05). CONCLUSIONS: There is hope that a viable treatment exists for Leishmania infection.
Zenodo (CERN European Organization for Nuclear Research) · 2019 · 0 citations · open access
Leishmaniasis: A neglected tropical disease
AbstractLeishmaniasis refers to a diverse spectrum of clinical syndromes caused by infection with protozoan parasites of the genus <em>Leishmania</em>. They are widely distributed across the tropical, subtropical, and temperate regions in 88 countries, 72 of which are in developing areas of the world. The diagnosis and treatment of the different syndromes produced by these parasites are particularly difficult in developed and non-endemic countries because of poor knowledge of clinical symptoms, diagnostic possibilities, and available treatment options. This article highlights the biology, life cycle, diagnostic, chemotherapeutic, and strategies to control Leishmaniasis.
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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