Over the holidays my family participated in an Escape Room, a live puzzle adventure game. We worked as a team to solve riddles, find clues and, over the course of 60-minutes, complete an old town bank heist. Many of the successful clues came from unexpected places – coordinates on maps, numbers inscribed in hidden places, and physical features of the room itself. Other clues seemed promising, but ultimately led to dead ends. In the end, everything came together and we escaped with only seconds to spare.
And so it goes with the invention of new medicines. The approval of a new medicine is an Escape Room of sorts, but over the course of decades not minutes. And like an Escape Room, clues can come from unexpected places, with some leading to new insights and others leading to dead ends.
I was in an Escape Room state-of-mind as I read a Science Translational Medicine article that developed a system to differentiate blood cells into microglia-like cells to study gene variants implicated in neurodegenerative disorders (here). In this blog, I provide a brief summary of the study, and then describe the potentially interesting phenomenon of genetically driven tissue-specific pathogenicity.…
In my previous blog series I talked about why genetics is important in drug discovery: human genetics takes you to a target, informs on mechanism of action (MOA) for therapeutic perturbation, provides guidance for pre-clinical assays of target engagement, and facilitates indication selection for clinical trials.
Here, I provide an overview of a new blog series on how genetics influences decision-making during drug discovery. The key principle: human genetics establishes a disciplined mindset and a firm foundation – anchoring points – for advancing targets through the complicated process of drug discovery. [For those less familiar with drug discovery, the end of this blog provides a brief primer on the stages of drug discovery.]
I highlight three areas: establishing a balanced portfolio, identifying targets with novel MOA, and creating a framework for objective decision-making. In subsequent posts, I will focus primarily on how human genetics informs on the latter (decision-making), with blogs pertaining to designing assays for screens and target engagement, utilizing pre-clinical animal models, predicting on-target adverse drug events, and selecting indications for clinical trials.
1. Establish a balanced portfolio
Whether in academic research, a small biotech company (see here) or a large pharmaceutical company (such as Merck, where I work), a balanced portfolio of projects is very important.…