BSc (Hons) MBChB (Hons) FRCP PhD FMedSci
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.
At last month’s European Huntington’s Disease Network meeting, Prof Sarah Tabrizi proudly announced that, in partnership with Isis Pharmaceuticals, Inc, she will be the lead investigator of the world’s first clinical trial of a huntingtin lowering (sometimes called ‘gene silencing’) drug for Huntington’s disease.
Called Isis HTT-Rx, the drug is an antisense oligonucleotide or ASO that has shown success in reducing production of the harmful mutant huntingtin protein and improving symptoms in animal models of HD. The multi-centre, multi-national trial will investigate the safety of increasing dose levels of Isis HTT-Rx and will be led by Prof Tabrizi and her team at UCL Institute of Neurology.
Watch Prof Tabrizi’s presentation on Isis HTT-Rx and the clinical trial:
Later, Dr Ed Wild and Dr Jeff Carroll interviewed Prof Tabrizi to find out more about how the trial will work and what it means for patients and families:
We are pleased to announce that Professor Sarah Tabrizi has been elected to the Fellowship of the Academy of Medical Sciences – Academy Fellows are elected for excellence in medical research, and her work in Huntington’s disease has been instrumental in her being elected. The hard work and support of her HD research team and the HD clinic team over the years, as well as all the many hours that patients and families have given for our research, have been pivotal.
44 researchers from across the UK have been recognised for their contribution to the advancement of medical science by election to the Fellowship of the Academy of Medical Sciences.
Quoting from the Academy’s New Fellows 2014 press release they stated that:
‘‘Professor Sarah Tabrizi FMedSci, elected this year, studies the neural and cellular mechanisms behind Huntington’s disease. She has worked on the disease throughout her career to wide acclaim, and is said to have set the standard for studying other neurodegenerative diseases. In 2009, she helped set up the UK All Party Parliamentary Group on Huntington’s Disease to raise the profile of patients with the disease.
Professor Tabrizi is one of three former Academy mentees who have later been elected Fellows. Professor Tabrizi has worked closely with the Academy for many years, joining the mentoring scheme in 2002, and being an active member of our Academic Careers Committee. She said:
“My mentor and the Academy’s Careers team have had an influential role in several career decisions, and this support has been invaluable over the last ten years. It is very exciting to be joining the Fellowship, and I look forward to maintaining a close relationship with the Academy in my new role.”
The new Fellows will be formally admitted to the Academy at a ceremony on Wednesday 2 July 2014.
Further information is available via the following links:
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