BSc (Hons) MBChB (Hons) FRCP PhD
Professor of Clinical Neurology
This site aims to bring together information about our research projects in Huntington’s disease (HD) for patients, family members and health professionals.
Through the Huntington’s Disease Multidisciplinary Clinic of the National Hospital for Neurology and Neurosurgery, we offer expert care and involvement in cutting-edge research, including clinical trials and work to understand HD and develop new treatments.
Our group is the largest and most productive clinically-focused HD research group in the UK.
A new article by the UCL HD research team, in collaboration with colleagues at the University of Massachusetts Medical School, has just been published in Brain. The team, led by Professor Sarah Tabrizi have shown for the first time that switching off the mutant protein that causes Huntington’s disease can reverse abnormalities in living cells taken from patients with the disease.
The research team compared specific immune cells, called monocytes, from blood samples donated by Huntington’s disease patients and healthy volunteers. The cells from Huntington’s disease patients respond excessively when exposed to a chemical from bacteria that causes an immune response. This results in the cells producing increased levels of inflammatory molecules. Inflammation is usually beneficial in helping clear infection, but in excess it can be damaging to the brain and other tissues.
To reduce levels of the mutant protein, the team went on to take advantage of the cells’ natural ability to engulf and digest foreign agents, such as bacteria and fungi. The cells were fed sugar-coated glucan particles containing a drug molecule (siRNA) that partially silenced the mutant huntingtin gene, leading to a reduction in levels of the harmful protein. This dampened the excessive response of the cells to immune stimulation.
“This is the first time that disease-associated alterations in cell function have been reversed in cells taken directly from Huntington’s disease patients,” said Professor Tabrizi. “That lowering of the toxic form of the huntingtin protein reverses the effects of the disease in easily obtained blood samples from patients, offers encouragement that such treatments may have similar effects in the brains of patients to slow the process of degeneration in Huntington’s disease.”
Drugs that aim to ‘silence’ the mutant protein are likely to enter clinical trials in the next few years, and this research is the first time that a drug that partially reduces the levels of the mutant protein has some beneficial effect in cells from Huntington’s disease patients, suggesting that the protein does not need to be completely depleted to delay or reverse harmful effects of Huntington’s disease.
Green glucan-encapsulated siRNA particles (GeRPs) are taken up by human immune cells to effectively silence huntingtin in these cells. This reverses the hyper-reactivity of Huntington’s disease white blood cells.
HD researcher Dr Ed Wild underwent a lumbar puncture last week, to experience first hand what the procedure feels like – and to donate valuable cerebrospinal fluid for Huntington’s disease research.
Ed volunteered for the procedure as part of our HD Biomarkers study. CSF surrounds the brain and shares some of its chemical makeup, so studying CSF is a really important tool for understanding brain changes in HD. Measuring levels of the huntingtin protein in CSF is also important for the global effort to develop gene silencing drugs for HD and begin clinical trials.
“It went very smoothly,” says Ed. “The anticipation was worse than the actual procedure. The local anaesthetic stings a bit, but that stops after about ten seconds. Then all I felt was a bit of pushing. Some people get a headache afterwards but I was fine. I had some mild back discomfort the next day, but was able to exercise normally.”
Ed’s CSF will be sent, along with that of our other patient and control volunteers, to Italy where our partners at IRBM Promidis are developing new tests to measure levels of the huntingtin protein, in a study supported by the CHDI Foundation.
Ed holds the sample of his CSF after the lumbar puncture procedure
Dr Ed Wild, Clinical Lecturer in Neurology in the UCL Huntington’s Disease Research Group, is planning a new study called HD-CSF, and would like to hear your thoughts on the proposal.
HD-CSF will focus on collecting cerebrospinal fluid (CSF) from people with Huntington’s disease. The CSF will be analysed to see whether we can measure levels of the mutant huntingtin protein that causes HD, and also measure the balance of protective and harmful chemicals produced by the brain’s immune cells.
These measurements are important for testing drugs currently being developed for HD and will hopefully speed up the start of clinical trials of new treatments including ‘gene silencing‘ and KMO inhibition.
CSF is collected by lumbar puncture, also known as a ‘spinal tap’, a minor procedure where a needle is used to withdraw about 4 teaspoonfuls of fluid from the base of the spine. It takes about 15 minutes and is done under local anaesthetic.
If you’d like to hear more about the proposal, and offer your thoughts on the design of the study, please get in touch.
On Thursday 20th June at 6:45pm there will be another chance to see the award-winning Huntington’s disease documentary Do You Really Want to Know, from Academy Award winning director John Zaritsky.
The film will be screened on the opening night of UCL’s Open City Documentary Festival, followed by a panel discussion featuring experts including UCL’s Prof Sarah Tabrizi – head of the UCL HD research group – and Dr Jeff Carroll, the HD researcher and mutation carrier featured in the film.
The film follows three families who have been confronted with the decision of whether or not to be tested for Huntington’s Disease (HD) – an inherited degenerative neurological illness that strikes in adult life.
Through three emotional, inspiring and surprising stories, viewers will learn how different people have faced the decision, and how they responded to their results – either hearing the worst news imaginable, or the best news of their life.
‘Do You Really Want to Know?’ won two Golden Sheaf Awards: Best Documentary (Science/Medicine/Technology) and Best Director (Non-Fiction) at the 2012 Yorkton Film Festival; a Chris Award for Best Science & Technology Documentary at the 2012 Columbus International Film & Video Festival; and Best Documentary the 2012 Okanagan International Film Festival.
The screening is endorsed by the UCL / UCLH Biomedical Research Centre.