An amino acid given together with iron can prevent malaria,
according to new research.
The study, by a scientist from the Medical Research Council's
National Institute for Medical Research (NIMR; now part of
the Francis Crick Institute) working with colleagues in
Japan, shows how 5-aminolevulinic acid (5-ALA) works in combination
with iron (in its bivalent form, or Fe2+) to inhibit the
growth of Plasmodium, the parasite that causes malaria.
The research follows previous investigations into photodynamic
therapy using 5-ALA by the Japanese researchers, from the
University of Tokyo, the Tokyo Institute of Technology and SBI
Pharmaceuticals. 5-ALA is the first compound in what's known as the
porphyrin pathway - the biochemical pathway for the synthesis of
haem, a component of haemoglobin in blood that carries oxygen
around the body.
Concentrated 5-ALA can be used to accumulate porphyrins -
intermediate molecules in the haem synthesis pathway - in cells
that are infected with Plasmodium. These accumulated porphyrins
then kill the parasite following irradiation with light. However,
direct irradiation of blood is unrealistic - which is a major
deterrent to the commercialisation of 5-ALA.
The Japanese team has previously shown that giving 5-ALA and
bivalent iron together can inhibit the growth of P. falciparum
without the need for irradiation. For the current study, Shigeharu
Sato of NIMR collaborated with the Japanese scientists to uncover a
critical step in how this works.
They showed that the combined use of 5-ALA and bivalent iron
causes porphyrins to accumulate in certain organelles in the
parasite. This generates active oxygen which, in turn, inhibits the
parasite's growth.
Dr Sato said: "These findings are expected to lead to the
development of new products to treat malaria. The safety of 5-ALA
and bivalent iron has already been established and clinical
development is expected to take place shortly.
"With fewer side effects expected compared to many of the
existing antimalarial drugs, 5-ALA and bivalent iron are expected
to be revolutionary antimalarial drugs that can be administered for
prophylactic purposes."
The paper, Synergy
of ferrous ion on 5-aminolevulinic acid-mediated growth inhibition
of Plasmodium falciparum, is published in the Journal
of Biochemistry.