Plenge Lab
Date posted: October 5, 2016 | Author: | No Comments »

Categories: Drug Discovery Human Genetics

I have many fears, both professional and personal. When I decided to leave academics for a job in industry in 2013, my biggest fear about making the transition was scientific. In my mind, I had a model of how human genetics might transform drug discovery and development. There were anecdotes (e.g., PCSK9 inhibitors) and a few systematic studies in specific diseases (e.g., genetics of rheumatoid arthritis), but there were many holes to the model. Over the last couple of years, additional anecdotes and systematic analyses have emerged (e.g., Matt Nelson, et al. Nature Genetics), which helps to soothe my fears…but I still have concerns.

[Disclaimer: I am a Merck/MSD employee. The opinions I am expressing are my own and do not necessarily represent the position of my employer.]

As I have blogged about previously, I see two primary routes to go from human genetics to new drug discovery programs (see here, here). The first requires that there are genes with a series of disease-associated alleles with a range of biological effects, ideally from gain- to loss-of-function (allelic series model). The second requires disease-associated genes to aggregate within specific biological pathways, which can then be turned into assays for disease-relevant pathway-based screens such as phenotypic screens.…

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