Pharmacogenomics in Pediatric Rheumatology
Pharmacogenomics in Pediatric Rheumatology
Investigating the role that genes play in drug response seems an attainable goal, now more than ever, with the rapid technological advances made available over the last decade. However, to date, the inconsistent findings and lack of reproducibility of results have highlighted the challenges we face in pharmacogenomic research, complicated further when applied to children with rheumatic disease.
Challenges in executing these types of studies are not insurmountable, but require adequately powered studies that utilize well defined phenotypes and validated and agreed-upon outcome measures. Although pharmacogenomic studies have traditionally taken a candidate gene approach to study the genetic contribution to drug outcomes, we have learned that these single genes do not operate in isolation, but rather as components of a more complex network. Just as disease pathogenesis involves multiple genes and regulatory loops, drug response likely does not involve a single drug target, but rather a multigene complex with its own regulatory features and salvage pathways. One must also consider that nominally similar conditions (such as JIA and RA) have very different phenotypes and causes, and importantly, drug pathways/systems are not necessarily the same in children at different stages of maturation as in adults.
Although not commonplace yet, this knowledge and approach may allow the identification of 'outlier' patients who represent the extremes of response and ultimately offer them safer and more effective therapeutic options.
Conclusion
Investigating the role that genes play in drug response seems an attainable goal, now more than ever, with the rapid technological advances made available over the last decade. However, to date, the inconsistent findings and lack of reproducibility of results have highlighted the challenges we face in pharmacogenomic research, complicated further when applied to children with rheumatic disease.
Challenges in executing these types of studies are not insurmountable, but require adequately powered studies that utilize well defined phenotypes and validated and agreed-upon outcome measures. Although pharmacogenomic studies have traditionally taken a candidate gene approach to study the genetic contribution to drug outcomes, we have learned that these single genes do not operate in isolation, but rather as components of a more complex network. Just as disease pathogenesis involves multiple genes and regulatory loops, drug response likely does not involve a single drug target, but rather a multigene complex with its own regulatory features and salvage pathways. One must also consider that nominally similar conditions (such as JIA and RA) have very different phenotypes and causes, and importantly, drug pathways/systems are not necessarily the same in children at different stages of maturation as in adults.
Although not commonplace yet, this knowledge and approach may allow the identification of 'outlier' patients who represent the extremes of response and ultimately offer them safer and more effective therapeutic options.
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