Resistance Fighters

Earlier this year, Michael Gale, Jr., Ph.D., was just getting over an upper-respiratory bug that swept through his lab. “It’s another example of the power of infectious diseases,” quips Gale, who leads UW Medicine’s Center on Innate Immunity and Immune Disease (CIIID).

In a conversation that began with a discussion of Ebola research at the CIIID, Gale — a basic scientist by training — talks about a pathway to immunity, RIG-I, that may benefit Ebola research and many other areas. He also touches on the significant challenges posed by drug development.

What is RIG-I?
RIG-I is a protein in our cells that recognizes viruses as foreign invaders to the body. Our lab and other labs identified it a number of years ago, and then we helped determine its 3-D structure. We learned that you can turn it on and turn it off using specific molecules. When it’s on, it triggers a cell’s immune response, and the cell will fight viruses.

Why is this research significant?
The problem with a lot of antiviral medications is that they target a specific viral gene. Then, when the virus mutates or develops resistance, the medication stops working. When RIG-I is working, the cell is activated in an antiviral state, and the virus can’t replicate. And not only that, the virus can’t easily develop resistance against this response because it is so complex. If we can figure out how to harness this pathway, we may have a solution for a lot of virus infections and the illnesses they cause: Ebola, flu, Dengue virus, West Nile virus and more.

What’s challenging about this work?
Conceiving a discovery in your lab as a drug target: that’s easy. You can just use your imagination. Actually getting to the point of developing a drug — I have a whole new appreciation for pharmaceutical development. You could have the best molecule ever. You could have something that cures cancer, but if you can’t formulate it for delivery as a medicine, for something that the body can actually use, it’s dead in the water. Formulation is extremely difficult.

Where are you now with RIG-I?
We’ve had really good success with a molecule that helps RIG-I take on Ebola, and we now have a whole spectrum of different compounds that work against a broad spectrum of viruses as potential therapies that we’re testing with Kineta Pharmaceuticals, one of our partners.

Final words?
Seven years ago, when I was writing all this stuff about RIG-I on a whiteboard, trying to convince everybody to join in the research, they were all going, “ahh, I don’t know about this.” What blows my mind is that it actually works!

Read our story on Ebola research at UW Medicine.

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