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.
We are delighted to accept donations to support our research, to help us understand and treat Huntington’s disease. Please donate via our UCL fundraising page.
A new measure has been developed which can explicitly characterise compensation in Huntington’s disease (HD) gene-carriers prior to clinical diagnosis. Publishing in EBioMedicine, the research team working on the study hope that identifying patterns of compensation in preclinical HD will not only improve understanding of neural mechanisms underlying HD pathology, but also provide potential targets that can be used in the testing of HD therapeutics.
HD is a neurodegenerative disease and despite considerable neuronal loss, preclinical HD gene-carriers are able to maintain normal behavior during many motor and cognitive tasks. This suggests that some form of compensation is taking place which enables those in the early stages of the disease to function normally. However, until now, there has been no experimentally-testable model of compensation to investigate this.
The international team of scientists from the Department of Neurodegenerative Disease and the Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, UCL Institute of Cognitive Neuroscience, Albert Ludwigs University of Freiburg, University Hospital Salpêtrière Paris, University of Leiden, University of British Columbia, University of Ulm, University of Iowa, and Monash University Melbourne and the CHDI Foundation have developed a new model which uses functional and structural Magnetic Resonance Imaging (MRI) to investigate potential compensatory associations between behaviour and brain activity in preclinical HD patients. Using variability in levels of brain atrophy to mark disease severity, the research team have shown that in those HD gene-carriers with the most significant neuronal loss there is localised compensation in the right hemisphere during cognitive processing, while comparable function in the left hemisphere appears to deteriorate.
“In demonstrating hemisphere-specific compensation in preclinical HD gene-carriers, we have provided potential targets for the future planned testing of disease modifying agents in the preclinical phases of HD where it may be important to monitor for preservation of compensatory activity.” said Prof Sarah Tabrizi of UCL Institute of Neurology.
Furthermore, as HD is caused by a single gene mutation and fully heritable, it is an ideal model for studying not only the earliest stages of HD, but neurodegeneration generally, as it possible to predict who will develop the disease many years before symptom onset.
“By using this model we can gain insight into the more common protein-misfolding neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, which are largely sporadic and are therefore much more challenging to study in the preclinical phases.”
A new paper by Dr Ed Wild in collaboration with scientists from University College London, IRBM Proidis, University of British Columbia, University of Iowa , The University of Gothenburg and CHDI foundation has just been published in The Journal of Clinical Investigation.
The paper describes a new ultra sensitive test that has been able to measure for the first time the build-up of a harmful mutant protein in the nervous system of patients during the progression of Huntington’s disease. The test is able to detect single molecules of mutant huntingtin in the cerebrospinal fluid of HD patients, including people who carry the gene but have not yet developed symptoms.
“We think the mutant huntingtin is being released into the CSF from the very brain cells it is killing,” said Dr Edward Wild of UCL Institute of Neurology. “It may be a smoking gun that reflects the harm the protein is doing in the living human nervous system.”
As well as detecting the protein for the first time, the researchers found that the level of mutant huntingtin was higher in volunteers with more advanced disease and the concentration of mutant huntingtin predicted the severity of movement and cognitive problems in patients.
2015 will see the start of the first human clinical trial of a gene silencing or huntingtin-lowering drug, which specifically aims to reduce production of mutant huntingtin in the brains of HD patients. Being able to detect and measure the amount of mutant huntingtin present in the nervous system will be a valuable way of seeing whether the gene-silencing drug is hitting its target and has the intended effect, lowering the amount of disease causing mHTT protein. Meanwhile, this new technique will be an invaluable tool to help researchers study the effects of this devastating disease in the living nervous system.
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: