New Genetic Priority Score Unveiled to Improve Target Prioritization in Drug Development

Driven by the need for a better way to prioritize targets for drug development, the Icahn School of Medicine at Mount Sinai has led the development of a new “genetic priority score” (GPS) that will integrate various types of human genetic data in a single easy-to-interpret partition.

The article, titled “Development of a priority score guided by human genetics for 19,365 genes and 399 drug indications,” is published in the January 3 online issue of Natural genetics.

Studies have shown that drugs have an increased likelihood of success in clinical trials when the genes they target have been shown to have genetic support. The new tool integrates multiple sources of genetic evidence to prioritize these drug targets.

The score measures the general ability of a gene to be targeted by drugs; Genes with a high score in the new tool are more likely to succeed as a drug target. The score identifies both known genetic targets of the drug as well as potential new therapeutic targets.

“We constructed a genetic priority score inspired by the realization that diverse human genetic data provide information about drug targets, but there was an absence of a coherent strategy for integrating these different types of data into an easily interpretable score “So we developed a computational scorecard to prioritize drug targets for enhanced drug discovery,” says Ron Do, Ph.D., senior author of the study and the Charles Bronfman Professor of Personalized Medicine at Icahn Mount Sinai. Remarkably, several genes with high GPS were already known to be targeted by approved drugs, validating the new tool.”

GPS, through its potential to streamline target prioritization, is able to have a significant impact on drug development. According to the researchers, it provides a valuable resource for researchers seeking to optimize the selection of drug target genes to improve the efficiency of the drug development process.

“The rising cost of drug development, running into billions, is mainly due to numerous clinical trial failures, highlighting the inefficiency of drug development pipelines. It is essential to improve target prioritization at an early stage “Studies consistently show that drug indications with human genetic support are more likely to pass trials and gain approval,” says study first author Áine Duffy, a Ph.D. candidate in Dr. Do’s laboratory.

The researchers are encouraged by these developments, but emphasize that this represents only a first step toward prioritization and the need for careful monitoring and further investigation of high-scoring target genes. Next, the investigators plan to refine the model by incorporating additional genetic features and evaluating more sophisticated algorithms to construct GPS.