An emerging medicine to treat infectious diseases

Carlos Fioravanti

Brazilian and American scientists have demonstrated that a compound known as P-Mapa is active against Mycobacterium tuberculosis in vivo. These results they say may pave the way for the use of this compound in the treatment of tuberculosis and other infectious diseases on humans.

P-Mapa is the acronym for a compound chemically classified as the proteinaceous aggregate of ammonium and magnesium phospholinoleate-palmitoleate anhydride. It has been developed since the 1990s by a group of Brazilian, Chilean and American scientists led by the non-profit research network Farmabrasilis. Tests on TB and other pathogens were carried out in the US by the National Institute of Allergy and Infectious Diseases (NIAID) teams.

According to the Farmabrasilis website,  mice are exposed to an aerosol of M. tuberculosis and later treated with P-Mapa and the antimicrobial Moxiflaxin, both used alone and combined. According to the researchers P-Mapa has acted alone to deter the bacterial proliferation in the lung and spleen on levels above the minimum standards required.

Apparently, the P-Mapa has synergized with Moxiflaxin, as the combination of the two drugs has provided a wider protection than each one used alone. Consequently, the P-Mapa compound it is believed may continue to be evaluated in higher doses, alone and in combination with other antimicrobials drugs.

P-MAPA is classified as an immunomodulator, meaning it helps to control the immune system activity improving the proliferation or the activity of white blood cells, as well as modulating the production of key substances in the body’s defenses called cytokines, as demonstrated in various studies on animal models and pilot studies on humans. This data indicates that P-MAPA may be broadly active, helping to deter intracellular microbes causing infectious diseases such as tuberculosis and malaria.

“Recently we identified some of the cell’s surface proteins, or toll-like receptors, triggered by P-Mapa in human cells, such as macrophages and dendritic cells, explaining one of the possible mechanisms of action and the versatility of this molecule”, Iseu Nunes, Farmabrasilis CEO, says.

In 2009, Farmabrasilis and NIAID teams showed that P-Mapa can protect against Punta Toro Virus (PTV), which produces a fatal hepatic disease in animals and is closely related to the Rift Valley fever virus, endemic in sub-Saharan Africa. In these experiments P-MAPA was able to protect 100% of infected animals, as detailed in a study published in the Antiviral Research journal. According to Nunes, this result could be the basis for testing this compound to treat viral hepatitis.

A plan to fight infectious diseases

Based on the data from preclinical and clinical studies the Farmabrasilis team has proposed the use of P-Mapa to fight infectious diseases. According to the proposal, the focus is the re-establishment of the patients’ immunocompetence by adjuvant immunotherapy with P-MAPA, so treating or preventing diseases such as tuberculosis and malaria in patients, including those co-infected with HIV.

“We are discussing with Brazilian and international institutions how to move this approach forward”, Nunes says. “We have already proven that P-Mapa is safe and can be very useful. Also, we can share all data and methods of production, free of charge, to governments, institutions or groups interested in using the P-Mapa to treat infectious diseases, also free of charge.”

Collective effort

The development of P-Mapa is a rare case of collaboration between non-academic and academic groups in Brazil, where most medicine candidates discovered in research institutes hardly go beyond the publication of papers, and Brazilian pharmaceutical companies only produce drugs derived from plants as well as generic medicines.

Created by the Brazilian physician Odilon da Silva Nunes, who passed away in 2001, the compound has attracted other non academic or academic physicians and scientists, NGOs, governmental institutions and entrepreneurs who have been working voluntarily to conclude its development and to explore other uses. “We hope to offer this medicine to [those] who most need it as soon as possible”, Iseu Nunes says.

A low cost medicine

P-Mapa was originally intended for cancer treatment and has been shown to have markable anti-tumor activity. Later, experiments carried out in Brazil and in the US on animal models and on humans have shown that the compound could help to prevent the advance of viruses, bacteria and protozoans, “with no relevant adverse effects observed”, Iseu Nunes adds.

P-Mapa is obtained from Aspergillus orizae by a low cost, fungal classical fermentation. In late 1990, Farmabrasilis teams, led by Iseu Nunes and Prof. Nelson Duran, Farmabrasilis scientific director, scaled up the production of P-Mapa. Currently the compound is produced in 100-liter fermentors in a pilot-plant under GMP conditions. “The production could be widened quickly if necessary”, Iseu Nunes affirms.

November 2010

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• Carlos Fioravanti is a science writer based in Brazil and former Reuters Institute for the Study of Journalist at Oxford University, UK. He has just completed his PhD at UNICAMP, the University of Campinas, about the course of the Brazilian compound P-Mapa. He has studied the development of new medicines in Brazil, the UK and the US.