“Over the last 15 years, the annual number of approved new drugs has been declining dramatically. Meanwhile, the pharmaceutical industry, as well as academic and government researchers, have dramatically increased the amount of money spent on drug discovery and development. Why is the large increase in funding not translating into new medicines?”—Brent Stockwell

In an essay for Rorotoko, Brent Stockwell, author of The Quest for the Cure: The Science and Stories Behind the Next Generation of Medicines, examines the challenges confronting scientists and pharmaceutical companies. Stockwell explains, “Drugs function by interacting with, i.e. attaching to, specific proteins within the body, which are called ‘drug targets.’ However, only 2% of the proteins found in humans have been targeted with drugs.” He continues, “The majority of proteins are considered undruggable. These proteins control nearly every disease process, from many types of cancer to neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Lou Gehrig’s, to many other diseases.”

In an effort to spur the development of new medicines the Obama administration has created a new center within the National Institutes of Health. While this is encouraging and will help bridge the gap between expensive research and commercial use, Stockwell warns that there are challenges:

But there is a more significant challenge to discovering new medicines than simply bringing basic discoveries to market. So if the new NIH center were to focus on a simple catalyst role, it would represent a lost opportunity.

The more fundamental challenge to discovering new drugs involves the basic science issue of protein druggability. It is this that could have a far more significant impact on the number and type of future medicines.

It is possible that new technologies and approaches could solve the challenging problem of protein druggability. However, if we abandon the undruggable proteins, we abandon the hope for truly transformative medicines. We must be able to translate the vastly detailed molecular networks emerging from basic science studies into therapeutics.

Currently, many of the root causes of diseases are considered undruggable and cannot be addressed directly with medicines. If we could solve the mystery of protein druggability, we could open up a vast number of possibilities for new medicines, and ultimately end the drug discovery crisis.