Exciting news! There is a new drug trial beginning for a treatment of Huntington’s Disease (HD). HD is a truly nasty disease. It tends to onset in your forties and slowly robs you of your personality, your bodily function and your cognitive abilities. Worse, it is a genetic disease that is inherited in an autosomal dominant manner; this means that it’s a fifty fifty toss up for each of your children as to whether or not they will also go on to develop the disease. Over the course of a decade or more you will lose everything that made you you and there is absolutely nothing you can do about. There are no treatments, nothing that will slow it down and nothing that might save your children suffering the same fate. Until now.
That’s the hope, in any case. The trial is led by Professor Sarah Tabrizi, a vibrant doctor who has dedicated her career to the study of HD with a view to finding a cure for this most brutal of illnesses. I know this because I have worked with her and her group on a number of occasions over the last decade at the National Hospital for Neurology and Neurosurgery (the press all seem to be saying she’s from University College Hospital, that’s the Trust we work for but we’re all based at the NHNN).
The treatment works by harnessing one of nature’s own mechanisms for protecting itself from harm, gene silencing. The genes in our DNA are the blueprints for making our proteins but there are a couple of intermediate steps along the way, one of these is called messenger RNA or mRNA for short. Sometimes the mRNA molecules are not made correctly and cells use short molecules that pair up with the defective mRNA to target it for destruction. The new drug works by targeting the mutated form of the HD causing gene, huntingtin, thereby stopping it from ever forming the mutant protein in the first place. In affected patients the mutant protein will go on to destroy brain cells particularly in the region known as the striatum.
The new trial is designed mainly as a test of safety. 32 patients will have ever increasing doses of the drug injected into their spinal cord over the course of 4 months. Samples will be taken throughout the trial, however, to measure levels of mutant huntington protein and the hope will be that this will go down whilst any side effects remain tolerably low. Hopes are high, trials of the drug in mice saw the desired decrease in mutant and a commensurate improvement in motor function.
HD was one of the first diseases I worked on and I have made lasting friendships both with the people working to find a cure and those desperately waiting for one to save their family. We currently have nothing. This new treatment may not prove to be a cure but it isn’t unreasonable to hope that it might be effective at slowing the progression of the disease. At this stage even that would be a fillip to those who labour under the Damoclesian shadow of HD.