NATURE:  STILL THE BEST PROVIDER OF CURES

MANILA, December 24, 2005
 (STAR) STAR SCIENCE By Gisela Padilla-Concepcion, Ph.D. - We know that there is a high incidence of infectious diseases such as tuberculosis, malaria and AIDS in our country, and drug resistance to currently used drugs is a major concern. I think that the long-term control of TB, malaria and AIDS should involve the use of local natural resources, local human samples, and local health scientists and health workers. The Philippines can provide two major sources of novel molecules that can be explored for developing new anti-infective therapies. These are the rich biodiversity of lower life forms and the large number of human disease samples. The Philippines could benefit directly from therapeutic products developed from these sources. Filipino patients would gain direct access to the treatment, which would be affordable and suited to their particular form of the disease.

The Philippines’ terrestrial and marine biodiversity could yield novel compounds with potent anti-TB, anti-malarial, and anti-viral activity. Over the last 50 years, more than 80 percent of all antibiotics and anti-infective drugs were developed from compounds isolated from terrestrial plants and land-based microorganisms. Up to the present, marine organisms have been explored largely or only for cancer and other diseases that are important in developed countries. Because marine bioprospecting is a costly and difficult undertaking, it is pursued principally to yield high-value therapeutic products such as anti-cancer drugs.

Philippine marine biodiversity is the third highest in the world. It should now be explored as a source of new anti-infective compounds to help treat TB, malaria and AIDS, aside from cancer. The Philippine government has passed a law to regulate scientific studies and commercial bioprospecting of biological and genetic materials, and this law is now being enforced with simpler implementing rules and regulations.

There are already thousands of marine natural products reported in the literature over the last 30 years, including some compounds isolated from Philippine marine organisms. These are compiled in several databases abroad. These compounds should be reviewed, requested from laboratories abroad and screened for anti-infective properties. Their chemical structures could be evaluated, modeled and modified to fit and bind the known molecular targets associated with the TB, malaria and HIV pathogens.

The Philippines has another rich resource useful for TB, malaria and AIDS research – human disease samples. Clinical isolates could be a source of new strains or forms of the pathogens, and thus a source of new antigens and molecular targets. The new antigens could be the basis for designing new vaccines. The new molecular targets would be used to find new small molecule drugs. Samples from patients who have the disease in various forms and stages, and samples from patients who have recovered or are asymptomatic, with or without drug treatment, are potential sources of new therapeutic molecules. Survivors must have produced some antibodies and other proteins, and probably some small molecules, in their bodies to combat the disease. These molecules would be associated with the particular form of the disease, the strain of the pathogen, the genetic make-up of the patients, and would thus be most useful for the community or population from which they were obtained.

In order to collect human samples, the patient’s informed consent should be obtained. The patients should also be provided monetary compensation. It is important that the research conducted should follow strict bioethical principles and should be performed under utmost caution, using the highest-level containment facilities (P3 level). The health and safety of the researchers must be ensured. However, while diagnostic and therapeutic products can be developed using novel biomolecules obtained from the disease samples, the Philippines is not yet very competitive in this area due to limited capabilities in molecular biology and biotechnology. A thorough characterization of the new antigens and molecular targets would also require capabilities in the field of proteomics.

The small molecule or metabolite profile (metabolomics) of human samples obtained from various stages, forms and treatment of the disease could indicate the particular physiological state of the individual and his response to the pathogen. A human survivor would have metabolites which could act as important signals (inhibitors or activators) of mechanisms which may be critical in overcoming the disease or keeping it at a residual level. Sensitive analytical methods such as mass spectrometry are now available for detecting such small molecules in biological samples over a period of time. Metabolomics could contribute to modeling metabolic pathways which are affected in disease progression and regression. This then could form the basis of finding new natural small molecule drugs. (It is interesting to note that many of the classical anti-cancer drugs used today are DNA topoisomerase 2 or topo 2 inhibitors isolated or developed from plants and microorganisms, and yet small molecule topo 2 inhibitors from humans, which probably exist in normal cells in order to regulate the structure and function of human topo 2, have not been found and explored as models of anti-cancer drugs.)

It is not surprising that Nature provides us the best source of bioactive small molecules. These molecules, which have specialized functions in the source organisms, are products of a natural selection process that has been occurring throughout evolution. These compounds could be used in their natural form or can be chemically modified to produce new effective drugs for human health.

Since small molecule drugs are still the cheaper and more affordable drugs for TB, malaria and AIDS, I believe that research in this field should be pursued in our country. If necessary, we should collaborate with foreign laboratories that can transfer to us more advanced technologies. In the past, I had proposed that the Philippine government should set up a National TB (Natural Products) Drug Discovery and Development Program that it would support in a substantial way. To assist in the funding, foreign foundations would be invited to support the program. Foreign experts would be invited to help advance technology here. With the government’s bioprospecting regulations in place, this program would be feasible and could bring in a lot of funding and training for research on natural products, drug discovery and development. Further, the products developed could undergo pre-clinical and clinical trials in the Philippines.

The proposed initiative focuses on scientific and technological innovations. But the success of health prevention, diagnostic and therapeutic programs in a country depends not only on the potential to find and develop new drugs but also on the participation of key individuals and agencies in effective scientific research and education programs, health care and community service programs. The cooperation of various sectors of the health and science community in our country will translate into greater national self-reliance in dealing with public health problems, such as infectious diseases, in the long term.

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Gisela Padilla-Concepcion, Ph.D. in Chemistry, is an associate professor at the UP Marine Science Institute, Diliman, Quezon City, where she teaches graduate courses and heads the Marine Natural Products Research Group. E-mail her at gpconcepcion@yahoo.com.


 


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