Children's Mercy team looks at genetic information to help predict response to medications
Researchers at CMH have developed a method for predicting a patient’s response to medications using whole genome sequencing. Their work was reported Wednesday in the journal Nature Genomic Medicine.
Pharmacogenetics combines pharmacology and genomics to study how differences in a patient’s genome can affect an individual’s responses to a medication. Genetic information can help to predict whether a patient will benefit or may be at risk of an adverse reaction to certain drugs. This knowledge aids physicians to individualize treatment by choosing the best medication and dose, i.e. tailor the treatment towards a patient’s DNA. Until recently, the process of determining a patient’s DNA profile (‘diplotype’) for pharmacogenes from whole genome sequence data has been a slow process.
Members of CMH’s Center for Pediatric Genomic Medicine and the Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation including Greyson Twist and Dr. Andrea Gaedigk, worked together to develop software called Constellation to automate this process to allow the identification of a patient’s diplotype from whole genome sequencing. The software works by comparing a patient’s DNA with a catalog of previously defined diplotypes that are known to have a specific drug response. Constellation was developed and evaluated primarily for the CYP2D6 gene, which is involved in the metabolism of a wide variety of commonly prescribed drugs including pain medications such as codeine and drugs used to treat behavioral disorders such as ADHD. Many antipsychotics and antidepressants are also metabolized by the CYP2D6 enzyme.
The team at CMH plans to expand the work on Constellation to include other important pharmacogenes and to begin using the program to support clinical research aiming at improving the physician’s ability to tailor drug prescriptions to individual patients.