In the past decade, increasing amounts of dollars have been spent on drug development yet the amount of new drugs entering the market per year remains the same. Furthermore with 200 billion dollars of patents expiring in the past four years (Witty, 2010), innovative pharmaceutical companies will need to look at new approaches to discover drugs. With the human genome being sequenced in 2003, a new field of science was created and an optimistic future for drug discovery. The implications of personal genomes for drug discovery can be significant.
Now since we know the DNA sequence of our species, we can develop drugs specifically for different patient genotypes. This would mean drugs could be specifically tailored towards individuals to ensure they are getting the best treatment possible (Chadwick, 2011). Also drugs that do not work on normal patients could be, repurposed to be tailored to patients with rare genotypes. Furthermore we could use Genome-wide association studies to locate sequences that could cause variation in drug response or susceptibility to toxicity significantly improving dosage and designs of drugs (Daly, 2010).
Lastly understanding polymorphisms in humans specifically in CYPs could reduce adverse drug reactions in low therapeutic index drug such as warfarin, as we could tailor the right dose to the individual possibly reducing the amount of drugs that fail due to toxicity (Huang, 2006). With the personal genome, there is a possibility for drugs to be modified to the individual however although the concept seems simple unfortunately the process is extremely complex. With having the personal genome, doesn’t mean we can entirely focus on it to develop drugs . Environment and diet are significant factors in drug response and variability.
For example, comparing micro biomes of Caucasians and Japanese it was shown that one had significantly more expression of a specific bacterium to better digest sea-weed (Li-Wan-P, 2011). Just because individuals have the same genomic sequence, differences in micro flora, carcinogens, diet, stress, and environment can have significant impact on drug response making drugs specifically based on genomes complex. Furthermore there is a difference from sequencing the genome and understanding the function and biology of the genome which significantly effects drug development (Moore, 2000).
Tailoring a drug to act on a specific gene could cure a disease but it could also affect many other pathways causing negative overall outcome in the patient. It is important to note that we need a large data bank of information to find variations within genomes and whether they have a biological impact, this will likely occur in the future however currently methods of obtaining large scale data are limited (Torkamani, 2011). Another problem with the genome is that to determine function of a gene one must create a knockout of it.
Creating knockouts in mice could cause adaptations to occur to continue its survival hence it would be able to survive without the gene. In humans drugs would be created to reduce expression of a gene not to knockout, reducing expression may cause other pathways may develop to counteract it (Sams-Dodd, 2005). Hence we would have to create a drug that would act on the specific gene as well as the genes that create pathways to counteract the change but even then it doesn’t guarantee that other pathways will arise.
This makes the simple idea of a drug that acts on a specific gene in a human an extremely complex one. This complexity makes development of these drugs expensive, failure prone and high risk as these discoveries of counteracting pathways may be found a few years after initial success or even in clinical trials (Sams-Dodd, 2005). A possible solution could be to change the clinical trial process so that these drugs fail quickly rather than over years so that companies pursue this field rather than take traditional approaches.
The current FDA clinical trial policy “one size fits all” for clinical trials, to encourage development in drugging the personal genome the FDA might need to revise its policy to accommodate these complications and risks. Currently there have been small successes and without a doubt in the future, personal genomes could play a significant role in discovering new therapies, targets, and drugs. However currently with lack of tools, information and understanding as well as high costs associated with genome research this field is still in its infancy.
To use personal genomes for drug development we must first must understand the biology and function behind the genome rather than to immediately create drugs to target genes as we have now entered not only a new field of drug discovery but also a new field of biology. References (in order) Witty A. (2010) Research and develop.
The Economist: The World in 2011. Retrieved from http://www. economist. com/node/17493432. Chadwick, R. (2011). PERSONAL GENOMES: NO BAD NEWS? Bioethics Volume 25 Number 2, 62–65. Daly, A. K. (2010). Genome-wide association studies in pharmacogenomics. Nature Reviews Genetics 11, 241-246.
Huang, S., Goodsaid, F. , Rahman, A. , Frueh, F. , & Lesko, L. J. (2006). Application of pharmacogenomics in clinical pharmacology. Toxicology Mechanisms and Methods, 16(2-3), 89-99. Li-Wan-P, F. P. (2011). Barking up the wrong genome – we are not alone. Journal of Clinical Pharmacy and Therapeutics 36, , 125–127. Moore. (2000). Understanding the Human Genome. IEEE SPECTRUM, 33-35.
Torkamani, A. , Scott-Van Zeeland, A. A. , Topol, E. J. , & Schork, N. J. (2011). Annotating individual human genomes. Genomics, 98(4), 233-241. Sams-Dodd, F. (2005). Target-based drug discovery: Is something wrong? Drug Discovery Today, 10(2), 139-147.