Recipient organisationNovartis Institute for Tropical DiseasesSource-published name: Novartis Institute for Tropical Diseases
Funding£8.7M
PeriodJul 2011 — Mar 2016
In plain English
AI plain-English summary
Two experimental malaria drugs are moving toward human trials, while a new lab-grown parasite stage could unlock a cure for a relapsing form of the disease that has no safe treatment. The first drug candidate, KAE609, entered first-in-human trials in late 2010; the second, KAF156, is ready for formal preclinical safety testing. Both target *Plasmodium falciparum*, the deadliest malaria parasite. The bigger challenge is *Plasmodium vivax*, which causes repeated relapses because dormant liver stages—hypnozoites—reactivate months or years after the initial infection. The only drug that kills these hidden parasites, primaquine, requires a long course and is dangerous for people with a common enzyme deficiency, ruling out many patients in endemic countries. Researchers at the Biomedical Primate Research Centre have now cultivated liver-stage parasites from a simian relative of *P. vivax* in the lab for the first time, and shown that these stages respond to primaquine. If this system works for human *P. vivax*, it could allow researchers to screen for new drugs that safely eliminate hypnozoites, potentially ending the cycle of relapse that keeps *vivax* malaria a chronic burden across Asia, the Americas, and the Pacific.
View original technical description
Supported by a grant from the Wellcome Trust (078285), the Novartis Institute for Tropical Diseases in partnership with the Genomics Institute of the Novartis Research Foundation (GNF), the Swiss Tropical and Public Health Institute (SwissTPH) and the Biomedical Primate Research Centre (BPRC) identified two novel antimalarial drug candidates for the treamtment of falciparum malaria. The first one, KAE609, entered first in human trials at the end of 2010 abd the second one, KAF156, is ready to enter GLP-compliant preclinical development. P.vivax malaria is increasingly viewed as a serious disease that carries a high socio-economic burden globally but has been largely neglected. Primaquine , the only radical cure treatment, is long and contraindicated for many patients in endemic countries. P.vivax malaria drug discovery has been historically hampered by the lack of in vitro culture systems for the liver stages of the parasite and more specifically the hypnozoites - the cause of chronic relapse. Our collaborators at the BPRC used a simian parasite closely related to P.vivax to cultivate for the first time in vitro liver stages of the parasite that are specifically sensitive to primaquine. The pharmacological validation of this in vitro culture system suggests that this model could be sued to identify and/or optimize new vivax malaria drugs. This proposal is to capitalize on the above accomplishments and can be divided in two main modules; a first one dedicated to the preclinical and clnical development of the antimalarial drug candidates (KAE609 and KAF156) and a secoond consisting of a drug discovery portfolio focused on the discovery of novel radical cure therapies for P.vivax malaria and the target identification of P.falciparum active scaffolds.
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