Sarah Tabrizi is involved in HD at almost every level. She’s professor of clinical neurology at the National Hospital for Neurology and Neurosurgery and director of the Huntington’s Disease Center at University
College London and the National Hospital for Neurology and Neurosurgery, Queen Square, which serves more than 800 families.
She leads a large and busy clinical research lab. And she’s also the global head investigator for the new huntingtin-lowering trial from Ionis Pharmaceuticals and Roche, as well as an investigator on two other ongoing drug trials: Pfizer’s PDE-10 inhibitor and Teva Pharmaceutical’s LEGATO-HD.
How did you get involved in HD?
I started my PhD in 1996, working with [Anthony] Schapira at UCL. Tony took me to a nursing home just outside London where I got to know HD patients. I realized that this was a terrible disease, and also a disease I wanted to get involved in doing something for.
Tell us about the Ionis trial, which enrolled its first patient in October 2015.
The Ionis-HTT-Rx study is something I’m thrilled to be leading. I think it’s hugely important.
The drug is a chemically modified piece of DNA that sticks to the huntingtin messenger molecules, and reduces the amount of the toxic huntingtin protein made. People sometimes call it gene silencing, and that drug is known as an anti-sense oligonucleotide (ASO).
Work in animal models showed that reducing mutant huntingtin slows the disease and in some cases allows brain recovery. This trial aims to test the safety of huntingtin-lowering in patients.
What can we expect?
In this study, the numbers will be too small to figure out whether the drug has a beneficial effect on the disease. Because it’s a first-into-man ascending-dose study, the trial will last until late 2017. If it is safe and tolerated, then it will move forward into larger trial in which we will then test whether it’s modifying the disease and having beneficial effects in patients.
What other projects are underway?
I’m still involved in trying to understand how the brain breaks down in HD. I have a big project looking at how the brain compensates for the effects of the mutant HD protein.
On the lab side, we’re looking at the innate immune system, testing potential therapies in mouse models, and also working with cell models and human iPS stem cells to model aspects of the disease and test possible therapies in the cell dish. I’m also involved in looking at genetic modifiers of HD.
Much of your research has focused on biomarkers—why?
We want to be able to develop and test new therapies for HD. If we can’t measure the disease really accurately in early-stage participants, it’s going to be difficult to test new drugs. We need to have biomarkers of disease progression to know if the drug is hitting its target correctly, and whether the drug is modifying disease progression or pathogenesis.
How optimistic are you?
I think we still have a long way to go. But to me this is one of the most exciting times in HD. The Ionis trial is a milestone that families have been waiting for for decades. Many other things are coming through the pipeline. Eventually, over the next 10 to 15 years, I want us to be able to do trials toward preventing the disease completely in people who have inherited the HD mutation. These things will all take time—but it’s an important time we’re in.
This story was originally published in the Spring 2016 issue of Enroll!