Drug development

Three patients Tito, Vice and Fidel present symptoms of rheumatoid arthritis. Doctors can prescribe drugs such as dexamethasone to alleviate the inflammation at a standard dosage. However, while Tito gets better from the treatment, Vic and Fidel return to the specialist for different reasons. Vic does not seem to benefit from the treatment and still present symptoms of arthritis whereas Fidel presents signs of adverse drug reactions. Should a drug in such cases be taken off the market or does it simply tell us that one dose does not fit all?

How these three patients respond to the same treatment can be attributed in part to how their bodies metabolize or break down the medicine. Recently, scientists have been looking into minor variations in genes that may determine how individuals process certain drugs to pave the way for personalized drug dosage based on whether a person is a fast, slow or normal metabolizer. For fast metabolizers, giving an insufficient dose may mean therapeutic failure. For slow metabolizers, giving a normal dose may mean accumulation of the drug in the system leading to an overdose.

The benefits of personalized medicine extend to drug development itself, which takes an average of 12 years and billions of dollars to bring to market, from an original pool of some ten thousand compounds screened. By identifying likely responders to a drug based on a person’s genetic variation, the efficacy of a candidate drug for a subset of patients can be gauged more easily, thus shortening drug development times and reducing costs. We do not wan potentially harmful compounds to be released to the public. An increased understanding of inter-individual variability in drug metabolism and a push towards personalized drug dosage and patient stratification will help ensure that investments in drug development will translate to profitable business as well as guarantee that safer compounds are made available to patients.

Genes Don’t Lie

At the Disease Molecular Biology and Epigenetics Laboratory, based at the National Institute of Molecular Biology and Biotechnology in the University of the Philippines Diliman, we work on research projects that will contribute to the advancement of personalized medicine. We try and find explanations as to why you and I process drugs differently and therefore require different dosages of any one drug. In particular, we study the effects of genetic variations called “microRNA binding site single nucleotide polymorphisms”, or MiRSNPs, in the regulation of drug metabolizing enzymes such as cytochrome 3A4(CYP3A4) and the pregnane X receptor.

Our laboratory attracts some of the best students in the institute and has won many awards locally and internationally since it was founded only 4.5 years ago. It is an excellent training ground for aspiring molecular and cellular biologists, which include both graduate and undergraduate thesis students as well as more junior apprentices. While we are not necessarily working on the same project, our troubleshooting skills, insights and perseverance all come into play. It is overwhelmingly satisfying to witness students actually enjoy the science of discovery, especially when it involves fundamentally important research such as personalizing drug dosage.

Through our research, we hope to contribute to the burgeoning field of personalized medicine. In the long-term, we want to focus on the Filipino population and add to the existing database of SNPs (single nucleotide polymorphism) to ensure that gene variations observed among Filipinos are taken into consideration when prescribing drugs and/or determining dosage. We envision a future wherein patients are stratified into likely responders or non-responders to a particular medication, drugs are prescribed according to one’s genetic variations and drug development made more efficient and cheaper because of advantages afforded by molecular biology.

Written by:
Reynaldo L. Garcia, Ph.D.
National Institute of Molecular Biology and Biotechnology
University of the Philippines Diliman

Published by:
Department of Science and Technology-Science and Technology Information Institute (DOST-STII)