Huntington's disease is a devastating neurobiological illness that happens at the molecular level in the brain. The protein huntingtin can mutate, and when that happens, it doesn't fold correctly. While it might not seem like a big deal, it sets off a cascade of events and results in brain dysfunction that leads to a loss of cognition, a loss of motor function in large muscles, and eventually death.
It's not clear what causes these proteins to fold incorrectly, however when they do? A cluster begins in the brain. Picture a big wad of bubble gum tangled in long hair. Neurons get clumped together, and the toxic results are a disease for which there is no known cure. The Huntington's is progressive so while finding a cause is crucial, researchers also look for ways to slow the progression of the disease and allow patients to have a better quality of life for longer.
Researchers at University College London (UCL) have spent more than ten years working on a drug that targets the folded proteins and lowers the level of huntingtin is the bloodstream, slowing the progression of the disease. The first human clinical trial of the drug was not only safe and well-tolerated by the first group of study participants, but it also lowered huntingtin levels significantly.
Professor Sarah Tabrizi from the UCL Institute of Neurology led the trials which were and sponsored by Ionis Pharmaceuticals. There were a total of 46 participants in the study group, all with early onset of Huntington's disease. They were treated at nine study centers, with locations in the UK, Canada, and Germany. The drug is called IONIS-HTTRx but will likely be marketed under a more specific name if trials continue to go well. The drug is administered into the spinal fluid via injection, as it would not get through the blood-brain barrier any other way. Patients received the experimental drug or a placebo, in four doses initially. The trial was designed to track effectiveness as the dosage went up, so patients in the study had their dosages increased over the course of the research.
Professor Tabrizi stated, "The results of this trial are of ground-breaking importance for Huntington's disease patients and families. For the first time a drug has lowered the level of the toxic disease-causing protein in the nervous system, and the drug was safe and well-tolerated. The key now is to move quickly to a larger trial to test whether the drug slows disease progression."
In the study, levels of the mutant protein huntingtin were measured in the spinal fluid of the patients before they began treatment and after as well. The assay to detect the proteins was designed to be highly sensitive, for researchers to have confidence in the results. Depending on the dosage given, the study showed that the patients who received IONIS-HTTRx had significantly lower levels of the protein.
The research has not been published yet; however, Tabrizi and her team will be presenting their results at upcoming scientific meetings and submitting the work for peer review. Ionis partners with Roche Pharmaceuticals and recently announced that the participants who took part in the recent trials would be offered an opportunity to continue to use the medication. With Huntington's disease being so severe and affecting thousands of patients and their families, a drug that could slow the progression of it is almost a new lease on life for some. Check out the video to learn more about this breakthrough.