Brazilian drug improves the immunity of dogs with leishmaniasis

An immunomodulating drug known as P-MAPA has shown promising results against some types of cancer and infectious disease, including tuberculosis and malaria.

By Karina Toledo

Agência FAPESP – A study published recently in the journal Acta Tropica has shown that a drug developed in Brazil and known as P-MAPA (an abbreviation for protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride) has shown effectiveness in improving the clinical state and immunity of dogs with symptoms of leishmaniasis. According to researchers, the drug can aid the traditional treatment.

The study was conducted at the Universidade Estadual Paulista’s Araçatuba Veterinary School of Medicine (FMVA – Unesp) in Brazil and was funded by FAPESP.

Researchers chose 20 animals that presented at least three characteristics of leishmaniasis, including accentuated weight loss, alopecia, abnormal growth of nails, and lesions, particularly on the ear tips.

After confirmation of the diagnosis, the dogs were split into two groups. Half were treated with intramuscular injections of P-MAPA for 45 days. The other half received only placebo during the same period.

“The treated group presented signs of clinical improvement, particularly related to weight gain and muscle mass, recovery from cutaneous lesions and the growth of fur in areas affected by alopecia. We also analyzed a series of parameters to see if cellular immunity had increased,” explained Valéria Marçal Felix de Lima, professor at FMVA and coordinator of the study.

In infected animals, explained the researcher, cellular immunity tends to decrease as the disease progresses, which favors an increase in the parasite load.

To verify whether the drug could prevent this advance, the researchers biopsied skin from the animals’ ears and analyzed the parasite load in the samples using PCR (polymerase chain reaction).

At the end of treatment, the dogs treated with P-MAPA showed a 100-fold reduction in the parasite load observed at the beginning of treatment. Additionally, compared to the control group, P-MAPA treatment stimulated five times more production of a cytokine named interferon gamma (IFNγ), which is responsible for activating immune cells and inducing resistance to the protozoan that causes the disease.

However, treatment also reduced the quantity of another cytokine, known as interleukin 10 (IL-10), which is capable of deactivating defense cells and allowing proliferation of the pathogen.

For Lima, the results suggest that P-MAPA could be used aid in the treatment of leishmaniasis in dogs.

“The drugs available today do not completely eliminate the parasite. The dogs are subject to relapses. Furthermore, they are very toxic to the animals,” explained the researcher.

Until recently, Brazilian legislation prohibited the treatment of dogs infected by the Leishmania chagasi protozoan because it was thought that sacrificing such animals was the best way to prevent transmission to humans, which occurs through the bite of an infected Phlebotomus papatasi sandfly. “But the legislation is becoming more flexible and permits the treatment of animals,” explained Lima.

Although the researchers did not explore the mechanisms of action of the medication in the article published in Acta Tropica, previous studies have shown that P-MAPA is capable of stimulating certain cellular receptors related to intact immunity.

Considered an immunomodulator, P-MAPA has shown promising results in fighting some types of cancer and other infectious diseases, such as tuberculosis and malaria. Read more at http://agencia.fapesp.br/en/16026.

The Farmabrasilis research network – a nonprofit created in 2001 and formed by Brazilian, Chilean, European and U.S. scientists – developed the molecule based on existing substances in the Aspergillus oryzae fungus.

The article Improvement in clinical signs and cellular immunity of dogs with visceral leishmaniasis using the immunomodulator P-MAPA (doi: 10.1016/j.actatropica.2013.04.005) can be read at www.sciencedirect.com/science/article/pii/S0001706X13001034.