AMAZING, ORIGINAL AND PATHBREAKING RESEARCH OPENS DOORS PREVIOUSLY SHUT!!

By Nancy S. Wexler, Ph.D.

We owe a wonderful thank you and congratulations to the late Paul H. Patterson of Caltech. Paul trained in the golden age of Neuroscience at Harvard University. In 1991 he joined the faculty at Caltech and the Scientific Advisory Board (SAB) of the Hereditary Disease Foundation. He was a wonderful, creative and thoughtful member of our SAB for 23 years. Tragically, Paul died in 2014 of a glioblastoma at the age of 70.

Paul was an expert of making and understanding antibodies, including monoclonal antibodies. He understood the delicate interplay between the immune system and our neurobiology. The HD protein is one of the most gigantic in our bodies.

Paul ingeniously made a number of antibodies recognizing different parts of this huge protein.

Paul and my Dad, Milton Wexler, were very good friends. They appreciated each other’s independent, iconoclastic approach to life. The antibodies Paul created are named for my DAD, MW1-MW 8. Paul shared these antibodies with scientists throughout the world to make progress.

The Hereditary Disease Foundation remains proud to have funded Paul’s seminal path-breaking work.

Huntington’s disease (HD) poses unique challenges for cure hunters. The abnormal protein clumps up inside the cell and causes problems. Any therapy must actually get inside the cell to work. Alzheimer’s and Parkinson’s clump outside the cell so they are easier to target.

Paul developed an “intrabody,” an antibody fragment that works against a target within the cell. In the September 3, 2008 issue of the Journal of Neuroscience, Paul and his group published the discovery of a very successful intrabody called “Happ1” which targets only the abnormal form of the HD and leaves the normal one intact and functioning – a small miracle!

And this intrabody was used to treat Huntington's disease in a variety of HD mouse models. It actually treated the symptoms of HD, and even reversed the mouse’s symptoms. This was the miracle we were waiting for!!!!

Paul understood the gravity of the next phase of being a cure hunter! DELIVERY, DELIVERY, DELIVERY!!!!!!!!!!!!!!!!!!!!!!!

Especially of a brain disease, how do you target delivery of your therapy to the brain? 

All gene therapy trials face this obstacle. The current Ionis trial of HTTRx delivers their therapy through the spinal cord into the cerebrospinal fluid (CSF) CSF. This is a fine and appropriate way of delivering it.

But Paul Patterson always thinks big and out of the box. Our brain has a protective “coating” around it called “the blood- brain barrier.” It prevents lots of trash from getting in. But also prevents lots of therapies from getting in, including gene therapies which could actually cure HD. If gene therapies cured the disease, the earlier the treatment was given the better.

Paul and his postdoctoral student Benjamin E. Deverman began developing a virus that will cross the blood brain barrier. This is an extremely clever virus. The Hereditary Disease Foundation began supporting Ben as a postdoctoral fellow beginning in 2014.

Paul and Ben developed a whole series of viruses that are color coded with different fluorescent protein tags. They can light up different neurons in the central nervous system and the periphery.

Tragically, Paul died in 2014, shortly after Ben joined his lab. Ben understood that Paul named his antibodies “MW” after my Dad. He decided to honor and recognizes Paul’s amazing and important mentorship by naming each antibody after him: “AAV-PHPs.”

These incredible antibodies can be loaded with a gene therapy for HD. They can be delivered as a shot in the arm. They travel through the bloodstream and across the blood brain barrier into all parts of the brain. This medicine will treat all the neurons in the brain!!!!!!!!

Ben just published his phenomenal work in the June 26, 2017 issue of Nature Neuroscience. Bravo Ben, bravo posthumously to Paul H. Patterson!!!!!!!!!!!!!

The world is a safer and healthier place thanks to all your efforts!!!!!!!! We all can’t wait until the next gene therapy trial is launched with this amazing safe and direct to all parts of the brain cure for HD takes it next step!

Thanks to Paul and Ben for preserving against all odds and succeeding!