Understanding protein interaction to optimize drug discovery

Blog 01

Bret S. Stetka, MD

The human genome contains over 20,000 genes. And every single one of these encodes for a protein that has some function in our body. But just as crucial to both health and disease is how these proteins interact with each other: how they collaborate to drive specific biological processes, how they interfere with each other’s function, how they respond to invading pathogens or administered drugs.

The body contains a flurry of molecular mingling that scientists call the “interactome,” a term primarily used to refer to protein interactions. It’s a dance that researchers are starting to decode to understand our biology better and, hopefully, treat mental and medical disorders better.

At the forefront of this research is Scipher Medicine, based in Waltham, Massachusetts. Scipher’s unique technology resulted from a collaboration between researchers from Harvard University, Brigham and Women’s Hospital, the Dana-Farber Cancer Institute, and Northeastern University. It began in 2003 when Drs. Joseph Loscalzo and László Barabási started building a map of how specific protein interactions influence health. They were then able to correlate the genomic signatures associated with those protein profiles to particular disease states and expected responses to treatment.

Scipher intends to use their approach to understand the molecular underpinnings of disease and personalize therapy in a wide array of conditions. Say a patient has particular molecular characteristics that render them less likely to respond to a specific drug. Their physician can then use that information to select another treatment – one more likely to be effective and provide symptomatic relief. This would go a long way to improving patient care, all the while helping assuage the billions of dollars in wasted healthcare costs associated with patients not responding to their prescribed medications.

Initially, Scipher is focusing on rheumatoid arthritis (RA), a condition that affects up to 1% of the population. Their PrismRA® blood test helps identify patients who aren’t likely to respond to TNF inhibitor therapy, one of the most common treatments for RA. Presumed non-responders can then talk to their doctor about trying alternative medications.  

“Scipher’s technology is set up for massively parallel research in multiple disease areas. We can analyze molecular dysregulation across conditions or a spectrum of human diseases to identify patients with identical molecular phenotypes,” says Dr. Slava Akmaev, Chief Technology Officer and Head of Therapeutics at Scipher. “Strategically, we think about precision therapeutics where response rates are above 90%.”

While Scipher’s immediate goal is to improve and personalize RA treatment, along with reducing unnecessary prescriptions and healthcare costs, their team’s ultimate mission is to use interactome biotechnology to identify potential drug targets in any number of conditions. As Akmaev puts it, “We have a full commitment to take novel targets, get them into drug development, and launch clinical trials. That is our ambition in therapeutics.”