The Drugs for Neglected Diseases initiative (DNDi) welcomes renewed commitment from Japan’s Global Health Innovative Technology Fund (GHIT Fund) for its drug discovery programmes pursuing new drug candidates for the treatment of Chagas disease.
Safer, simpler, more effective treatments for Chagas are urgently needed. There are only two drugs available to treat the disease, both discovered half a century ago. While effective for some patients, existing treatments last eight weeks and sometimes have serious side effects.
The first new project follows previous GHIT-supported research on over 500 genes of Trypanosoma cruzi (T. cruzi) – the protozoan parasite that causes Chagas disease – which led to the identification of 25 molecular targets essential to the T. cruzi lifecycle. Each of these 25 entities were carefully examined for their potential as drug targets for the disease, leading to the selection of the T. cruzi autophagy-regulating* factor as a potential target for future Chagas treatments.
Together with the Japanese National Institute of Advanced Industrial Science and Technology (AIST), DNDi teams will now work to obtain hit compounds amenable to further development as novel anti-T. cruzi drugs acting against the selected target. Two different but complementary screening methods will be used: a fragment-based drug discovery (FBDD) approach, as well as an assessment of a library of T. cruzi active compounds identified from DNDi whole cell-based screens. The novelty of the selected target has the potential to offer breakthroughs in both the field of target validation and in lead generation for Chagas disease.
Two other GHIT-funded projects will focus on screening new compound libraries made available by two key DNDi pharmaceutical partners, including 37,000 compounds from Daiichi Sankyo Company, Limited and 25,000 compounds from Takeda Pharmaceutical Company Limited. These compounds will be processed in T. cruzi intracellular assays by DNDi partner Institut Pasteur Korea to identify hit series that meet GHIT/DNDi hit criteria and that could be advanced further in the drug discovery process. Both pharmaceutical partners will provide in-kind contributions to the projects, in addition to access to their compound libraries.
GHIT has supported DNDi R&D projects for neglected tropical diseases (NTDs) since 2013, including for Chagas disease, visceral leishmaniasis, cutaneous leishmaniasis, and mycetoma. GHIT support has also been critical to the success of the NTD Drug Discovery Booster, a global consortium of pharmaceutical companies collaborating to identify new potential treatments for NTDs.
About Chagas disease
Caused by the protozoan parasite Trypanosoma cruzi and transmitted by biting insects known as ‘kissing bugs’, Chagas disease is endemic in 21 countries in the Americas and is also present in Europe, Japan, and Australia. Chagas affects approximately 6-7 million people, with 30,000 new cases and 14,000 deaths per year. As people typically show no symptoms for many years, most are unaware they have the disease. Up to a third of people with Chagas will eventually suffer heart damage that can lead to progressive heart failure or sudden death. Chagas kills more people in Latin America each year than any other parasitic disease, including malaria.
About the Drugs for Neglected Diseases initiative (DNDi)
A not-for-profit research and development organization, DNDi works to deliver new treatments for neglected patients, those living with Chagas disease, sleeping sickness (human African trypanosomiasis), leishmaniasis, filarial infections, mycetoma, paediatric HIV, and hepatitis C. DNDi is also coordinating a clinical trial in 13 African countries to identify treatments for mild-to-moderate COVID-19. DNDi has delivered nine new treatments since its inception in 2003, including new drug combinations for visceral leishmaniasis (kala-azar), two fixed-dose antimalarials, and DNDi’s first successfully developed new chemical entity, fexinidazole, approved in 2018 for the treatment of both stages of sleeping sickness. dndi.org
Phone: +41 79 431 6216
* Autophagy is a self-digesting mechanism responsible for removal of damaged organelles, or malformed proteins.
Photo credit: Vinicius Berger-DNDi