Completed Brain & Nervous System Infection & Immunity

Discovery of New Leads for the Treatment of Human African Trypanosomiasis (HAT)

Funder Wellcome Charity-funded
Recipient organisation Novartis Institute for Tropical Diseases Source-published name: Novartis Institute for Tropical Diseases
Funding £2.0M
Period Jan 2014 — Dec 2015

In plain English

AI plain-English summary

Sleeping sickness kills thousands of people each year, and the drugs that treat it are toxic, difficult to administer, and often fail against the later neurological stage of the disease. The parasite that causes the disease, *T. brucei*, invades the brain, and no current oral medication can safely reach it there. Researchers at the Novartis Institute for Tropical Diseases have already identified 28,000 chemical compounds that kill the parasite in lab tests. Now they plan to systematically test all of these hits, using molecular and pharmacological tools they have developed in-house, to determine which ones can cross the blood-brain barrier, remain stable in the body, and are safe enough for human use. Through medicinal chemistry, they will refine the most promising structures, aiming to produce 2–3 lead scaffolds that could become cheap, orally available treatments for both stages of the disease. If successful, this would replace current injectable therapies with a simple pill, making treatment accessible in remote rural clinics across sub-Saharan Africa.

View original technical description
Novel treatments effective against both the acute (stage 1) and the neurological form (stage 2) of the Human African Trypanosomiasis (HAT) diseaseare urgently needed. Following up on an initial chemical screen of the Novartis libraries at the Genomics Institute of the Novartis Research Foundation (GNF), the Novartis Institute for Tropical Diseases (NITD) has carried out additional screens that collectively identified 28,000 hits with sub-micromolar potency against the HAT pathogen (T. brucei). NITD has either, developed in-house or enabled access to all the molecular and pharmacological tools required for the characterization of those hits and assess their efficacy, Distribution Metabolism Pharmaco-Kinetics (DMPK), safety, and developability (e.g. physico-chemical properties, formulation) properties. Using those tools, NITD propose here to carry out a systematic analysis of allhits and through exploratory medicinal chemistry activities expand our understanding of their structure activity relationship with the goal to identify those hits with the most favourable overall pharmacological profile. We anticipate this effort to produce 2-3 lead scaffolds likely to yield preclinical candidates with properties consistent with our target product profile of novel, cheap safe, orally available HAT therapies effective againstthe neurological stage of the disease.

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Researchers

Thierry Diagana (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Optimisation of a series of hits against trypanosome phosphofructokinase to give a lead for treatment of the neglected disease Human African Trypanosomiasis
NANOHAT: Development of a safer and more effective sleeping sickness drug.
Combination chemotherapy of Human African trypanosomiasis: the potential of drug synergism and the blood-brain barrier
Development and Commercialisation of a Second Generation Rapid Diagnostic Test (RDT) for Human African Trypanosomiasis (HAT) and other Kinetoplastida
MICA: Modes of action and resistance mechanisms towards anti-trypanosomal benzoxaboroles

Original classification

Seeding Drug Discovery Award

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.