5-ALA amino acid and iron combo point to revolutionary new anti-malaria drug

01 December 2013

Structural diagram of 5-ALA (5-aminolevulinic acid)

Image: Structural diagram of 5-ALA (5-aminolevulinic acid)

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.

  • Alongside colleagues in Japan, researchers at the Medical Research Council's National Institute for Medical Research have shown how the amino acid 5-aminolevulinic acid (5-ALA) and bivalent iron (Fe2+)can prevent malaria. The combination has already been shown to be safe and effective, and development of new antimalarials based on the research is expected. 
  • Malaria remains one of the most devastating diseases in the developing world - one report showed it caused 1.2 million deaths in 2010 alone. In Africa, a child dies every minute from malaria. The most commonly used drugs are failing rapidly due to resistance, alternatives are expensive and there is no vaccine.