Personalized medicine and genetic drug interactions – another long way to go

One hope for personalized medicine is that individuals would have their major gene variations profiled and that drug interactions with critical genes would also be profiled.  Thus, a person with a particular disease could determine whether a particular drug is efficacious given their gene variations, or whether that drug would be likely to produce an adverse reaction.  Fulfilling this hope requires both profiling of gene variations present in individuals and pharmacogenetic studies of drugs, that is, analyses and  clinical testing of how drugs behave in the presence of genetic variations.   I have discussed individual profiling in the blog entry Individual DNA testing. It is starting to get off the ground but has a very long way to go.  This blog posting is about progress/lack of progress in pharmacogenetic drug profiling. 

My comments are mainly based on a review article  that appeared in PloS ONE four days ago Fulfilling the Promise of Personalized Medicine? Systematic Review and Field Synopsis of Pharmacogenetic Studies.  The authors looked systematically at the published literature in an attempt to determine the current state of pharmacogenetic knowledge.  From 102,264 Medline hits and 1,641 articles from other sources, we identified 1,668 primary research articles (1987 to 2007, inclusive). A high proportion of remaining articles were reviews/commentaries (ratio of reviews to primary research approximately 25:1). The majority of studies (81.8%) were set in Europe and North America focussing on cancer, cardiovascular disease and neurology/psychiatry. There was predominantly a candidate gene approach using common alleles, which despite small sample sizes (median 93 [IQR 40–222]) with no trend to an increase over time, generated a high proportion (74.5%) of nominally significant (p<0.05) reported associations suggesting the possibility of significance-chasing bias. Despite 136 examples of gene/drug interventions being the subject of ≥4 studies, only 31 meta-analyses were identified. The majority (69.4%) of end-points were continuous and likely surrogate rather than hard (binary) clinical end-points.” 

The state of progress appears to be underwhelming.  The authors conclude “The high expectation but limited translation of the pharmacogenetic research thus far may be explained by the preponderance of reviews over primary research, small sample sizes, a mainly candidate gene approach, surrogate markers, an excess of nominally positive to truly positive associations and paucity of meta-analyses. Recommendations based on these findings should inform future study design to help realise the goal of personalised medicines.” 

So, more or less the same thing can be said about the pharmacogenetic profiling aspect of the personalized medicine hope:  It is starting to get off the ground but has a very long way to go. It is a long long way to Tipperary, to stem cell treatment and to drug-response related personalized medicine.  At least, we are on our way.

About Vince Giuliano

Being a follower, connoisseur, and interpreter of longevity research is my latest career, since 2007. I believe I am unique among the researchers and writers in the aging sciences community in one critical respect. That is, I personally practice the anti-aging interventions that I preach and that has kept me healthy, young, active and highly involved at my age, now 93. I am as productive as I was at age 45. I don’t know of anybody else active in that community in my age bracket. In particular, I have focused on the importance of controlling chronic inflammation for healthy aging, and have written a number of articles on that subject in this blog. In 2014, I created a dietary supplement to further this objective. In 2019, two family colleagues and I started up Synergy Bioherbals, a dietary supplement company that is now selling this product. In earlier reincarnations of my career. I was Founding Dean of a graduate school and a full University Professor at the State University of New York, a senior consultant working in a variety of fields at Arthur D. Little, Inc., Chief Scientist and C00 of Mirror Systems, a software company, and an international Internet consultant. I got off the ground with one of the earliest PhD's from Harvard in a field later to become known as computer science. Because there was no academic field of computer science at the time, to get through I had to qualify myself in hard sciences, so my studies focused heavily on quantum physics. In various ways I contributed to the Computer Revolution starting in the 1950s and the Internet Revolution starting in the late 1980s. I am now engaged in doing the same for The Longevity Revolution. I have published something like 200 books and papers as well as over 430 substantive.entries in this blog, and have enjoyed various periods of notoriety. If you do a Google search on Vincent E. Giuliano, most if not all of the entries on the first few pages that come up will be ones relating to me. I have a general writings site at www.vincegiuliano.com and an extensive site of my art at www.giulianoart.com. Please note that I have recently changed my mailbox to vegiuliano@agingsciences.com.
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