06/18/2012

Farmabrasilis in the journal Infectious Agents and Cancer

 

P-MAPA against TB and cancer (Infectious Agents and Cancer 2012)

 

Brazilian and American scientists announce the effects of P-MAPA on tuberculosis and cancer.

 

Scientists from the Brazil-based research network Farmabrasilis, in collaboration with Colorado State University and funded by National Institute of Allergy and Infectious Diseases (NIAID/NIH), have demonstrated that the immunomodulator P-MAPA is effective to treat bladder cancer and tuberculosis in animal models.

 

This result is due P-Mapa´s ability of activating specific cell receptors, called Toll-Like Receptors (TLRs), which trigger the organism immune response against microbes and tumors. The work is detailed in a paper published on  18^th June in the journal Infectious Agents and Cancer.

 

The results qualify P-MAPA as adjuvant to BCG, the classic treatment for bladder cancer. “P-MAPA can be used as a complement, when BCG does not work adequately”, Brazilian and American scientists state in the paper.

 

The results strengthen the arguments to carry out the clinical trials of P-MAPA to treat cancer and infectious diseases. In a clinical trial phase I with voluntary humans, P-Mapa was shown to be safe, and no relevant side effect was observed.

 

Previous studies had shown that P-Mapa was effective against other kinds of tumors, bacteria, virus and protozoans. 

 

This latest research was coordinated by Farmabrasilis and mobilized universities and research centers in Brazil and US, with funding from Farmabrasilis and governmental agencies in both countries.

 

The Brazilian team led the experiments on cancer and American scientists from Colorado State University did the tests on tuberculosis, using the most adequate animal models to evaluated the ability of P-MAPA to deter the development of infection. 

To access to the paper published in the Infectious Agents and Cancer in HTML or PDF format, go to:

http://www.infectagentscancer.com/content/7/1/14

 

 

or

 

 

PubMed: http://www.ncbi.nlm.nih.gov/pubmed/22709446

 

 

The abstract follows : 

 

Effects of P-MAPA Immunomodulator on Toll-Like Receptors and p53: Potential Therapeutic Strategies for Infectious Diseases and Cancer

 

 

Infectious Agents and Cancer 2012, 7:14 doi:10.1186/1750-9378-7-14

Published: 18 June 2012

 

Background

 

Compounds that can act as agonists for toll-like receptors (TLRs) may be promising candidates for the development of drugs against infectious diseases and cancer. The present study aimed to characterize the immunomodulatory effects of P-MAPA on TLRs in vitro and in vivo, as well as to investigate its potential as adjuvant therapy in infectious diseases and cancer.

 

Methods

 

For these purposes, the activity of P-MAPA on TLRs was assayed in vitro through NF-kappaB activation in HEK293 cells expressing a given TLR, and using an in vivo animal model for bladder cancer (BC). The antimicrobial activity of P-MAPA was tested against Mycobacterium tuberculosis (TB) in vitro in an MIC assay, and in vivo using an aerosol infection model of murine tuberculosis. Antitumor effects of P-MAPA were tested in an animal model with experimentally induced BC. Moxifloxacin (MXF) and Bacillus Calmette-Guerin (BCG) were used as positive controls in the animal models.

 

Results

 

The results showed that P-MAPA, administered alone or in combination with MXF, induced significant responses in vivo against TB. In contrast, the compound did not show antimicrobial activity in vitro. P-MAPA showed a significant stimulatory effect on human TLR2 and TLR4 in vitro. In BC, TLR2, TLR4 and p53 protein levels were significantly higher in the P-MAPA group than in the BCG group. The most common histopathological changes in each group were papillary carcinoma in BC group, low-grade intraepithelial neoplasia in BCG group and simple hyperplasia in P-MAPA group. Concerning the toxicological analysis performed during BC treatment, P-MAPA did not show evidence for hepatotoxicity and nephrotoxicity.

 

Conclusions

 

In conclusion, P-MAPA acted as TLR ligand in vitro and improved the immunological status in BC, increasing TLR2 and TLR4 protein levels. P-MAPA immunotherapy was more effective in restoring p53 and TLRs reactivities and showed significantly greater antitumor activity than BCG. The activation of TLRs and p53 may provide a hypothetical mechanism for the therapeutic effects in both cancer and infectious diseases. Taken together data obtained will encourage the further investigation of P-MAPA as a potential candidate for the treatment of cancer and infectious diseases.