According to Waleed Alabsi, Pharmacogenomics refers to the study of how the genetic makeup of a person affects their response to medications. This field done by Youscript System combines pharmacology and genomics to come up with effective and safe medications that are personalized and tailored to a person’s genetic makeup.
Adverse drug reactions contribute to a significant number of hospitalizations and death. Researchers are discovering how inherited differences in genes can affect a body’s response to medication. Genomics is used to identify whether a medication will work in a patient or it will result in an adverse drug reaction.
A significant cause of death and serious illness in patients according to Youscript is due to adverse drug reactions and causes difficulties in the pharmaceutical industry during drug development. Adverse reactions are classed as idiosyncratic reactions which are not caused by drug concentrations but due to unusual patient phenotype. Serious adverse drug reactions are classified as type A or B.
Waleed Alabsi says that Idiosyncratic adverse reactions are believed to affect different organs like the liver, skin, heart, and muscle, and kidney. In some drugs, hypersensitivity reactions can occur. Looking at drug withdrawals, the biggest number of compounds withdrawn from the market was because of either hepatotoxicity or toxicity affecting cardiac function. When the lever is affected by adverse drug reactions it shows heterogeneity in their phenotypic effect. These reactions are referred to as drug-induced liver injury (DILI). 10% of these hepatotoxic adverse drug reactions have the potential to progress to liver failure which can be resolved through a liver transplant.
According to Waleed Alabsi, an important feature of serious adverse drug reactions is genetic susceptibility. There is considerable interest that the development of genetic tests identifying all those at risk of adverse drug reactions before prescription might lead to the development of valuable drugs.
Pharmacogenomic approaches used to identify causative genes:
Research on pharmacogenomics by Youscript to identify genes that contribute to susceptibility to adverse drug reactions has involved case-control association studies through candidate feen approach or genome-wide association (GWA) analysis. Developments in GWA studies have contributed to considerable progress in complex disease genomics. This is considered the most appropriate approach to use in identifying causative genes in adverse drug reactions.
According to Waleed Alabsi, a few reasons have been identified for this. The genetic risk factors identified have large effect sizes and are generally found in biologically obvious genes. The advantage of GWA studies is their open approach where all gene variations are looked into. This advantage has led to the discovery of entirely novel associations that would otherwise have been unlikely to be predicted through candidate gene approaches. When detecting small defects, GWA is particularly valuable though the limitation with most studies on adverse drug reactions is that the number of study cases is small. Assembling large uniform cohorts can be challenging since the genetic risk factors for adverse drug reactions are drug-specific and not simply end-organ-specific.
Waleed Alabsi says that it is unlikely that GWA studies will identify all genetic risk factors that cause adverse drug reactions. There are rare variants that can only be detected by sequencing studies. Through exome sequencing where all coding of genes is a sequence, significant progress has been made in some diseases. This type of sequencing by the Youscript System has been most valuable in detecting variants in rare diseases that show Mendelian inheritance rather than in complex diseases. That said there have been some exceptions reported in the fields of infectious disease and type II diabetes. Where regulatory sequences are determined in whole-genome sequencing, it s necessary to provide sufficient sensitivity to spot rare variants that are relevant to adverse drug reactions.