PGNX in RUM: Summary

[Guest guest]

I am thankful to the very less number of respondents for their participation. I believe that the future lays in our GENES and off course the use of drugs as per our Genetic Make up. The era of amplichip is today. Tomorrow it will be the time for “GENECHIP” or we can call it the “GENECARD”. Very personal, very unique to each one. And hence the most rational tool for therapy…leading to the most rational way of therapy.. I would like to thank the contributors of discussion who had done valuable inputs to our discussion “The Role of PGNX in RUM”. Dr Swapnil for providing us the definition of RUM that is given by WHO as, "Patients receive medications appropriate to their clinical needs, in doses that meet their OWN INDIVIDUAL REQUIREMENTS, for adequate period of time, and at the lowest cost to them and their community." Dr Mangesh for giving us very comprehensive view on Pharmacogenomics as follows, “According to a famous ancient quote “what is medicine to some may be the fierce poison to others.” The same drug and in the same dosage may produce beneficial effects in many patients but can produce adverse effects in few. We already have data regarding the number of hospital admissions and deaths due to adverse drug reactions. We also know that the most important factor for such variable response to medicines is the genetic differences between the individuals. Pharmacogenomics is the new field that is bridging the gap between pharmacology, drug treatment and the patients. Pharmacogenomics

associates individual’s genetic make up with drug metabolism and treatment response. It takes into consideration all the causes of differences in the drug response which includes genes controlling the drug metabolizing enzymes, transporter proteins, signaling and cellular response pathways and cellular targets. Pharmacogenomcis holds the promise to use the current drugs more rationally, finding of the new drug targets, and development of new drugs. Now, how the knowledge of the molecular action of drug and genetic determinants of the drug response is to going to achieve the goal of giving the right drug at the right dose to the right patient and at the right time (RUM)? By looking at the genetic profile of the patients, the genes responding to a given drug by over-expression,

down-regulation or no response at all can be easily identified. So by this we can tell which are the genes involved in the drug response and expected side effects of the drug. Treatment strategies based on the population’s genetic profiles can be developed so that we can predict which are responders, non-responders and poor responders, also the patients who are prone to side effects. In conclusion, pharmacogenomics will be very helpful for the RUM: By looking at the genetic profile, best drug for the patient can be selected. Dosage adjustment can be made according to person’s genetics so avoiding the risk of adverse effects. Early selection of the optimal therapy will definitely increase the patient’s compliance to therapy.” And also about the ethical aspects in PGNX as follows, Though the development of personalized medicine is scientifically and clinically seems very useful to mankind, there are few ethical concerns: The pharmacogenomic data of the population may be utilized for the exclusion of the patients which are either adverse drug reaction prone

or not responding to research medicine, thus neglecting these patients from the clinical trial. As vast amount of the pharmacogenomic data will be available, maintenance of the confidentiality of it will be the most challenging task. Genetic profile of the patient will disclose the disease predisposition of that person, family members or entire ethnic group and abuse of such data can harm patient as well as entire population. Also, if the patient’s profile discloses any rare genetic disorder for which no treatment is available, then that may be the worst scenario for the

patient. Further I would like to mention the contribution of Dr. S. Ziaur Rahman regarding 1. Pharmacogenetics is generally

regarded as the study of genetic variation that gives rise to differing response to drugs, while pharmacogenomics is the broader application of genomic technologies to new drug discovery and further characterization of older drugs. 2. History as In the early 1950s, two interesting findings – prolonged muscle relaxation after curarization with suxamethonium in patients with congenital cholinesterase deficiency and acute hemolysis induced by antimalarial drugs (like primaquine) in patients with low G-6 PD activity set the stage for new developments. By the end of 1980s and 1990s, the causal genes coding for debrisoquine hydroxylase, or CYP2D6 had been cloned and

characterized, inaugurating a new field of Pharmacogenetics and Pharmacogenomic 3. the role of PGNX in RUM would greatly enhance our approach to unanticipated drug toxicity and would narrow the risk/benefit margin of drug therapy. Such an integrative strategy is a key element directed towards the promotion of optimal drug therapy. The concept of PGNX is not only a rational (RUM) but also profitable during drug discovery process (can earn 5 billion USD/year). The risk like 1 out of 10 pass clinical trials to market and 1 out of 20 recover development costs may maximally be minimized. Researches in this direction are being done in many places of clinical pharmacology. I know few scientists who are involved directly in this field such as Dr. Gaidgek (of USA who first time worked in gene deletion that explains slow metabolism), Professor Leif Bertilsson (of Clinical Pharmacology Dept, Karolinska Inst, Huddinge University Hospital, Sweden), Dr. Collen Masimirembwa (He has now started his own lab in Nairobi, Kenya. Earlier he was in AstraZeneca) , Professor Olavi Pelkonen (of Dept of

Pharmacology and Toxicology, University of Oulu). With the passage of time, we may take the advantage of this novel drug targeted PGNX; if not now, then our successors will definitely devour its fruits. PGNX as a part of RUM will improve human health. It will be helpful in both infectious diseases and noninfectious diseases, microbial drug resistance, where there is treatment failure, and in non-responders (30-60% of patients do not respond to treatment by available drugs). It will also help in drug intellectual property. Dr. Shilpa Jadav For providing an important article on The concept of personal drugs in the undergraduate pharmacology practical curriculum. Indian J Pharmacol 2007;39:165- 7 Dr Surendiran for enlightening us regarding funding agencies as There are enough agencies to fund research projects on genomics, which are remaining unutilized. These depot of resources like DBT, DST, ICMR, CEFIPRA etc are to be utilized by various institutions all over the country and set up

pharmacogenetic labs with personnel. This has a long way to go, with the current rate of progress in research. Dr. Buch For adding the link of following article from NEJM As

http://content. nejm.org/ cgi/content/ full/358/ 2/105?query= TOC Volume 358:105-107 January 10,

2008 Number 2 Letting the Genome out of the Bottle — Will We Get Our Wish? And lastly, the group owner Dr Vijay Thawani for giving me the apportunity to moderate on this forum. Thanks to all readers too. Regards, Dr Kiran

Chaudhari Lecturer, Pharmacology, GMC, Nagpur.

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