New class of compounds for treating malaria
18 July 2013
Researchers at the Instituto de Medicina Molecular (IMM), in
Lisbon, Portugal, have discovered that a class of compound called
Torins that were developed for treating cancer is a highly potent
Torins were originally developed by researchers in the US to
inhibit a key human protein involved in cell growth, mTOR, and have
been shown to be effective anticancer agents in rodent models.
The team at IMM team and their collaborators have discovered that
Torins appear to have a novel activity against the Plasmodium
parasites themselves, distinct from both currently used malaria
therapeutics and from their ability to target human mTOR. The study
has been published online in the journal PNAS.
Torins are capable of killing the cultured blood stages of the human
parasite, Plasmodium falciparum, the species which causes most
malaria deaths and severe disease, and are equally potent against the
liver stages of a model rodent parasite.
A single dose of the compound Torin2 delivered at the beginning
of the P. berghei liver stage is sufficient to eliminate
infection in mice before any Plasmodium parasites reach the blood.
"Given the alarming trend of resistance to our current antimalarial
therapies, this is really an exciting finding," says Dr. Mota, the
senior author of the study, "and we are already working to develop
Torin molecules suitable for clinical trials of antimalarial
activity in humans."
Plasmodium parasites progress through two different stages of
life in humans and other mammals, the first of which occurs in the
liver, and causes no symptoms of disease. The second stage of
Plasmodium life occurs in the red blood cells, and it is here that
the parasites can cause severe illness and death. Most current
antimalarial compounds target only the malaria parasites growing in
the blood, but a great need exists for compounds which could
successfully eliminate the parasites in the liver as well, before
they begin causing illness.
An estimated 220 million people are infected each year by
malaria-causing Plasmodium parasites, which are transmitted by the
bite of an infected mosquito. This enormous infection burden leads
to some 660,000 lives lost to malaria each year, the majority of
these young children in sub-Saharan Africa. While a vaccine to
prevent malaria remains elusive, we depend on antimalarial compounds
both to treat infections and prevent disease.