New strategies to combat malaria: heparin and nanomedicine

The Institute for Bioengineering of Catalonia (IBEC), the Barcelona Institute for Global Health (ISGlobal) and the biotech firm Bioiberica have signed a partnership agreement to study the development of new compounds derived from heparin to combat malaria.

The partnership, which was officially announced this morning at the BioSpain meeting in Bilbao, is based on the research undertaken by Dr Xavier Fernández-Busquets, head of IBEC and ISGlobal’s joint Nanomalaria unit, engaged in developing specific antimalaria therapies, and the R&D project of Bioiberica, world leader in heparin production, to seek new applications of this molecule.

Every year malaria infects 200 million people worldwide and causes half a million deaths. For several decades it has been known that when the malaria parasite enters the bloodstream, it invades the liver cells to produce thousands of merozoites – a stage in the life cycle of the parasite – that enter into the circulation and infect red blood cells, managing to evade the immune system.

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“Our first step was to demonstrate that heparin may block the entry of merozoites into red blood cells,” said Dr. Fernández-Busquets at a press conference at BioSpain this morning. “As such, inhibiting the growth of the parasite could promote the immune response against it.”

Not only that, but Dr. Fernández-Busquets’ group found that heparin shows specific binding affinity for infected red blood cells over uninfected cells. “This could allow the development of targeted therapies for malaria infected cells only, also based on heparin,” he adds.

So far, heparin has not progressed towards clinical applications due to its powerful anticoagulating activity; the amounts needed for malaria treatment could cause internal bleeding. The researchers are trying to solve this problem in three different ways.

Firstly, they’ve seen that the binding of nanoparticles to heparin minimizes its anticoagulant activity, so they’re explored the ability of heparin attached to nanoparticles to carry out two roles: as a carrier of other antimalarial agents, which would be encased in the nanoparticles, and as a drug itself.

Secondly, they’re studying the use of heparin as a drug against the life cycle stages of the malaria parasite that are found in mosquitoes. Direct administration to the insects eliminates the problems associated with anticoagulation and allows rapid development of the compound.

Finally, they’re testing in vitro 19 compounds of heparin derivatives that have been chemically modified to show low anticoagulant activity, which could open up new strategies against malaria based on stimulating the immune system to eliminate the pathogen more efficiently. Of these, eight showed significant antimalarial activity.

“We’ve finished a very interesting first phase,” concludes Dr. Fernández-Busquets. “These three strategies open new avenues towards designing new therapeutic approaches against malaria, and our results so far are very encouraging.”