Originally posted on sciy.org by Rich Carlson on Tue 07 Aug 2007 08:28 AM PDT
I believe that in India there is a whole hearted embrace of targeting ethnic drugs, however the Marketing name for the pharmaceutical industry is "personalized" medicine. This appears to be a press release for the pharmacos in India rc...
A promising segment of pharmacogenomics, personalised medicine has a lot to offer India which has world's most ethnically and environmentally diverse population. Sushmi Dey finds out
Imagine
next time when you visit your doctor for treatment, he asks you questions like—where
do you live and what do you do in addition to symptoms; before prescribing you
a medicine. And yes, there is everything official about it! Maybe because he
wants to find the medicine that 'fits' you the best. While researchers all over
the world are making efforts to bring a change to the conventional approach
to drug development which produces one drug for all, but benefits only a few.
Indian pharmacos and scientists are not very far behind. They are in fact collecting
the information necessary for the same.
A consortium of Indian scientists recently completed a genetic database and TCG Life Sciences is likely to become the first private player to use the database. "We have created a genetic database of 2,014 healthy individuals drawn from 55 populations of India covering over 800 million people. It will be helpful in deciding population based characterisation of good and poor effect of drugs," says Prof Samir K Brahmachari, Director, Institute of Genomics and Integrative Biology (IGIB). The use of this database is expected to have large implications on both affordable public healthcare system as well as successful launch of a drug in specific region of India by pharmacos in India.
TCG Life Sciences is also undertaking a research project under The Centre For Genomic Application, a collaboration between Institute of Genomics and Integrative Biology (IGIB) and TCG. "The project is not aimed at discovering drugs but data which can tell which drugs will suit which sect of population," says a company source. The company also has plans to undertake projects in close collaboration with Indian Statistical Institute (ISI).
New vs conventional
The new knowledge of genomics has unleashed the possibility of more effective diagnosis, therapeutics and patient care and consequently a patient friendly healthcare.
Human beings are unique individuals and have small yet crucial differences, when it comes to genetics. These differences are often due to environment, diet, age and lifestyle. All these factors influence a person's health, disease and hence the response to medicines. The response of a drug depends on individuals' genetic factors, age, metabolism, lifestyle and nature of work. Researchers assert that a drug working well in population may not show the same affects in another population.
However, pharmacos adopt a generalised approach to drug development. Pharmacos develop drugs under a particular system with a particular size to fit all kinds of patients. This system is commonly known as "one size fits all" system. The idea behind this conventional system of medicines is to develop drugs to which an average patient will respond. This is done because currently there is no simple way to determine various individuals' response to a certain drug and also there is a lot of time and cost involved in the process of drug development.
Researchers believe that there can be a more focused, personalised and customised way of treatment wherein variations can be used to understand the genetic predisposition of ethnic groups to diseases and predict how a particular patient responds to a specific drug and prescribed accordingly. "Physicians realised that Primaquine, a drug used to prevent relapses of Vivax malaria, produced hemolysis in a few patients. They realised that patients were deficient in an enzyme G6PD which led to the hemolysis. This was however not seen in all patients. Thus the concept 'individualising drug therapy' was born in the 1950 and today is called pharmacogenetics. This primarily focuses on understanding inter-individual variation in response to drugs. The field hopes to achieve the goal of giving the right drug to the right patient in the right dose to maximise efficacy and minimise toxicity," says Dr Neelima Khirsagar, Dean, KEM Hospital.
The idea
The march towards personalised or customised medicines will narrow down the research to a personalised level. The concept of personalised medicine talks in detail about an individual's genetic make-up and need. This stream of pharmacogenomics promises to examine individuals' genetic inheritance and their variations that have an impact on drug response. Variations of genes are responsible for the disease phenotype and response of drug. "There is a 0.1 percent variation observed in the human genome sequence. As a consequence of the genetic variability among individuals, the response to drugs varies extensively among populations," says Brahmachari.
With the use of this science, researchers are keen on exploring ways to predict how a patient will respond to a drug. With the concept of personalised medicine, the patient's medication or treatment can be selected on the basis of detailed information about the patient's genotype and clinical data.
The working
Since the concept of personalised medicines is primarily based on the genetically determined variations, rapid identification of human genes and gene variations that might influence disease is the most important step. The first step in this process is to associate the occurrence of a particular gene variant with the incidence of a particular disease or disease predisposition. According to Personalized Medicine Coalition (PMC), a Washington based NGO, personalised medicine uses new methods of molecular analysis to better manage a patient's disease or predisposition toward a disease which varies from one individual to another depending on environmental and circumstantial factors. The results are in the form of biomarkers. Biomarkers are biological molecules that are stable and predictive and indicate a particular disease state. The development of biomarkers help in more focused and targeted drug development. "Biomarker analysis can also help classify sub-groups of patients who have the same molecular variation of the disease, enabling one to monitor its progression, select appropriate treatments and measure the patient's response to medication," explains PMC. "The natural variations (DNA polymorphisms) found in our genes play a role in our risk of getting or not getting into certain diseases. The combination of these variations across several genes, along with numerous external factors such as environment, diet and exercise affect each individual's risk," states PMC. These genetic variations are also responsible for the working of a same drug in different manners in different individuals. Reason being, variations in DNA can lead to differences in how drugs are absorbed, metabolised and used by the body. "When a medicine/drug is ingested by an individual, it undergoes the processes of absorption, distribution, interacting with the target site to produce an effect, metabolism and excretion," says Khirsagar.
Therapeutic usage
While identification of genetic variation can be helpful in all therapeutic areas, some significant areas are likely to be extremely benefited by personalised medicines. For instance, cancer genetics is a sub-specialised field of genetics. Recent reports suggest that cancer pre-disposition genes and families are being identified by genetic testing. Researchers also assert that personalised medicines can be instrumental in identifying families at risk for cancer, heart diseases and diabetes. Indian pharmacos like TCG Life Sciences and many scientists are also involved in several projects related to diabetes, cardiovascular problems, neurodegenerative disorders, cancer and epilepsy where personalised medicines can make a big difference.
Switching to personalised medicines also means powerful medicines with less side-effects, improvements in the process of drug discovery and approval process and consequently a reduction in the overall cost of healthcare. Genes play a very important role in the response of an individual's usage of therapeutic drugs. Understanding these genetics variations and their interactions with environmental factors will help pharmacos produce better predictive and diagnostic molecular tests and drugs. According to Brahmachari, many drugs show adverse reactions to specific individuals. Agrees Dr I C Verma, Head-Department of Genetics, Sir Ganga Ram Hospital and adds, "The ability of metabolism differs from individual to individual. A patient with faster metabolism is given a higher dose of drug and one with slower metabolism is administered with a relatively slower dose medication. If a patient with slower metabolism is given a higher dose, the medicine will work faster and can get accumulated and may lead to negative reactions."
No effects on pharmacos either
Personalised medicine also has benefits for pharmacos in terms of business. There are several blockbuster drugs that are intended to suit population in general. However, since there is no simple way to identify who actually benefits from the drug, many physicians generally prescribe expensive drugs to all patients. However, pharmacos often face severe difficulties when such drugs have adverse side-effects on many patients. Calling off a blockbuster drug from the market also means a heavy loss to the industry.
"Our effort is to use pharmacogenomic tools to identify cheap drugs or drugs that are withdrawn due to side-effects, in order to retain them in the market by discovering individuals for whom the drug will have good efficacy and no ADR. This diagnostic then can allow usage of drugs that would have been out of the market but will be available to sub-set of large patient pool as low cost healthcare," informs Brahmachari.
Challenges to face
Although personalised medicine is a promising segment for pharmacos and its consumers, there are some challenges in its way to success. Introducing a drug in market would involve a lot of capital. Whether pharmacos will be ready to develop and introduce drugs that serve only a small portion of the population remains a question to be answered in future. Personalised medicines would mean executing an extra diagnostic step to find out which drug will benefit which patient. This will require a comprehensive knowledge about the genes involved in drug response. Hence, educating healthcare providers and physicians to interpret the diagnosis correctly and recommend the best course of treatment is a major challenge.
Genetic testing is poised to challenge privacy, confidentiality and patients' rights. Patient protection is clearly a critical issue without which it will be impossible to collect the molecular and clinical data that is the foundation of personalised medicines. According to PMC, the pathway to the development of personalised medicine is marked by the need to identify and address a range of public policy issues. The implications for current systems, such as healthcare payer and physician incentives, medical records privacy and clinical trials ethics must be explored by all stakeholders, who will need to reach an agreement on what modifications should be made. "Identification of genetic or proteomic markers specific to non-responders or associated with the ADR is the challenge of tomorrow towards the development of personalised customised medicine," avers Brahmachari.
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