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 international Biospain meeting held in Bilbao.

This partnership is based on the research undertaken by Dr Xavier Fernández Busquets, head of IBEC and ISGlobal 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. 

Malaria infects 200 million people each year and leads to half a million deaths worldwide. Several decades ago it was scientifically established that when the malaria parasite enters the bloodstream, it invades the liver cells to produce thousands of merozoites (a phase in the life of the parasite) which re-enter the bloodstream, where they infect red blood cells and succeed in going undetected by the immunity system. “Our first step was to show thatheparin can block the binding and entry of merozoites to the red blood cells. By inhibiting the growth of the parasite it could promote the immune response against itself”, explained Dr Fernández Busquets this morning at the press conference, which forms part of the international Biospain meeting held in Bilbao.

In addition, by way of fluorescent microscopy, cell selection assisted by fluorescence and force spectroscopy of individual molecules, the group of Dr Fernández Busquets discovered that heparin shows specific binding affinity for infected red blood cells compared to uninfected blood cells. “This could enable the development of specific antimalarial therapies for the infected cells also based on heparin” he adds. However, heparin has not progressed towards clinical applications due to its anticoagulant activity (the amounts needed for treatment could provoke internal bleeding). 

“We want heparin to return to being the first line of treatment to combat malaria; this is thereason for this joint project between industry and two research institutes. Bioiberica can bring to the table all of its expertise and scientific know-how of heparin and the IBEC and ISGlobal its know-how of nanomedicine and malaria”, declares Joan Bassa, heparin Director of Bioiberica. 

To this end, three lines of research are involved.

Firstly, we are exploring the capacity of heparin bound to nanoparticles (this binding minimises its anticoagulant activity) to play a dual role: as a targeting element of other antimalarials and as a drug in itself.

Secondly, the use is being studied of heparin as a drug against the phases of the malaria parasite that are found in its other host: mosquitoes. Direct administration to insects would eliminate the problems related to anticoagulation and would enable fast development of the compound.

Finally, in vitro testing of 19 compounds derived from heparin, that are chemically modified and with a low anticoagulant capacity, is being conducted. This could open up new strategies against malaria based on stimulation of the immunity system to be able to eliminate the pathogen more efficiently. Of these, 8 have shown significant antimalarial activity. 

“This first phase has concluded very successfully. All three are strategies that pave the way to the design of new therapeutic approaches against malaria and this has encouraged us to keep investigating”, concludes Mr. Fernández. Busquets.