This Monograph describes the state of art of the immunomodulator P-MAPA, that has been scientifically studied since the 80s by Brazilian, Chilean, European and American scientists.
Its chemical and physical characteristics, biological properties, pre-clinical results and clinical trials results will be detailed and discussed, in order to explore its potential uses as a therapeutic.
As the experiments confirmed, P-MAPA is a immunomodulator, on of a large group of therapeutics chemicals that helps to control the immune system activity improving cytokines production.
Cytokines are small proteins secreted primarily by immune system cells that promote the proliferation and/or differentiation of others cells and play a significant role in the regulation of the extend the immune response.
They are also the first-line of defense against viral agents and are critical for induction of subsequent specific immune responses.
Examples of cytokines include interleukins (IL-2, IL-7, IL-12), the interferons (IFN), hematopoietic colony stimulating factors (GM-CSF) and proinflamatory factors such as tumor necroses factor (TNF).
Such cytokines operate on lymphocytes by stimulating them to proliferate and by this means, boosting a hosts immune response.
The immunotherapy was consolidated as a valuable therapeutic option as a result of accumulated scientific knowledge and the development of new pharmaceutical products that can act effectively on the immunological system. However, some serious limitations prevents the unrestricted use of these compounds. This kind of therapy is still costly, prolonged and associated with significant side effects.
For these reasons, it is not suitable specially for certain groups of patients, e.g. in the hepatitis C patients.
In face of the strategic role of immunotherapics, it is highly desirable that new compounds capable of acting on the inmunological system are developed and made available rapidly in order to contribute to own the actual therapeutic arsenal.
P-MAPA has exhibited important biological properties when used in cellular systems, in experimental animals and in preliminary assays in humans. These include the capacity to combat infectious diseases and cancer.
Preclinical and clinical studies have demonstrated substantial amplification of immune responses by P-MAPA.
In summary, P-MAPA induces stimulatory effect on human toll-like receptors, proliferation of lymphocyte T, increases cytokine production (mainly interferon-gamma and Interleucin -2), and increases NK cell activity and stimulate NO release by macrophages , resulting in therapeutic effects in a remarkably wide range of pathologies -- as expected for an immunomodulator -- including infectious diseases and cancer, both in animal models and in humans.
Among other properties, this pharmaceutical displayed in animal models the ability to reestablish a healthy immune system when this is challenged by infectious or neoplasic processes.
The immunosuppression reversion associated to P-MAPA has also been observed in experimental models for infectious diseases, and resulted in the protection of the host and in high survival rates of animals, even for those experimentally infected with lethal doses of infectious agents.
In view of these properties the P-MAPA development is focused on intracellular pathogens in animal models of bacterial, viral and protozoan infections.
The product is a strong candidate for use as adjuvant drug in the treatment of infectious diseases, caused by intracellular pathogens,such as Tuberculosis and Malaria, since an ineffective immunity in these infections is often associated with a depressed Th1 cytokine response and reduced production of interferon-gamma.
In several animal models for cancer study, P-MAPA has been clearly demonstrated an ability to revert tumor-induced immunosuppression. This has been associated to a significant therapeutic impact on the primary disease and its metastatic process.
P-MAPA given either prior or after tumor inoculation or bacterial infection, increased the number of bone marrow granulocyte-macrophage progenitor cells (CFU-GM). Its encouraging in this context consider P-MAPA for combination chemotherapy to protect the host from hematotoxicity as well as to supplement the tumoricidal efficacy.
The experimental data obtained so far in many biological and pathological systems led us to postulate P-MAPA as a immunotherapic with has a large spectrum of clinical use.
In contrast with most if not all other immunomodulators, it has an ample safety margin for clinical use, since no significant side effects have been observed in any of the experimental models tested.
In accordance with these data, P-MAPA is being proposed as a medicine for using in cancer and immunodeficiences, e.g. in AIDS, as monotherapy or adjuvant therapy with the current therapies.
The increase of CD4 and CD8 lymphocytic population due the use of P-MAPA, even in the presence of pathologies, is the basis of another promising field of application : As adjuvant of antiviral treatment in Hepatitis B and Hepatitis C, mainly when the medication of immunomodulation of the first choice for instance, Interferon -alfa, exerted some limitation in its use, due to side effects or failure in the therapeutic response, among other factors.
In the case of Hepatitis C, the stimulation of CD4 and CD8 population, under the HCV infection on hosted, is being considered as an important factor to improve the patient recovering ( Pawlotsky et al).
Also the ability of P-MAPA to increased the NK cell activity may be important for terapeutic use, as hepatitis C infection has been shown to decrease NK activity (Kawarabayashi N, et al).
FONTE: Farmabrasilis 16/10/2008