UCL HUNTINGTON’S DISEASE RESEARCH

INFORMATION FOR SCIENTISTS, CLINICIANS, PATIENTS, RELATIVES AND CARERS

UCL HUNTINGTON’S DISEASE RESEARCH

Sarah J Tabrizi

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.

Latest Huntington’s disease research news, provided by HDbuzz

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UCL Huntington’s Disease Research Fund

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.

 

Latest news

11th December, 2017 - Drug lowers deadly Huntington’s disease protein

The first drug targeting the cause of Huntington’s disease was safe and well-tolerated in its first human trial, led by UCL Huntington’s Disease Centre, and successfully lowered the level of the harmful huntingtin protein in the nervous system.

 

https://www.ucl.ac.uk/news/news-articles/1217/111217-huntingtons-disease-protein

All press queries should be directed to j.behagg@ucl.ac.uk.

9th November, 2017 - Professor Sarah Tabrizi wins the 2017 International Leslie Gehry Brenner prize for Innovation in Science

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Professor Sarah Tabrizi

Professor Sarah Tabrizi  has received the 2017 International Leslie Gehry Brenner prize for Innovation in Science.

Awarded by the Hereditary Disease Foundation on November 6 in New York, the $100,000 prize is in recognition of “her outstanding contributions to innovative clinical trials and to clinical care for people with Huntington’s disease and their families.”

The award committee commended Professor Tabrizi for her work advancing the mechanistic understanding of Huntington’s disease pathobiology and developing novel therapies for Huntington’s disease (HD).

The prize was donated by architect Frank Gehry and his family, in memory of his daughter Leslie who died of cancer in 2008.

Professor Tabrizi co-founded the UCL Huntington’s Disease Centre in 2016 with Professor Gillian Bates, who won the Leslie Gehry Brenner Award in 2012 for developing the first mouse model of HD.

Professor Tabrizi’s research programme seeks to discover effective disease-modifying treatments that prevent or reverse the neurodegenerative process in HD. She leads a research group that follows two distinct but complementary approaches: basic science focusing on cellular mechanisms of neurodegeneration, and a programme to translate those findings into treatments and cures. She and her collaborators have developed means of identifying and measuring the HD gene and its protein in human blood and cerebrospinal fluid (CSF).

She leads a team at the UCL Huntington’s Disease Centre that is currently conducting a trial of a novel ‘gene silencing’ treatment for HD, sponsored by Ionis Pharmaceuticals. It’s the world’s first trial in patients to slow, stop, prevent or reverse HD, using a method that targets the root cause of the disease, a gene producing a protein called huntingtin.

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Professor Sarah Tabrizi with Dr Nancy Wexler (President of the Hereditary Disease Foundation) and Dr Alice Wexler (a member of the Board of the Hereditary Disease Foundation)

She has published over 250 peer-reviewed publications to date, she was elected a fellow of the UK Academy of Medical Sciences in 2014, and in 2010 helped set up the UK All-Party Parliamentary Group for HD.

Professor Tabrizi said: “I am honoured to receive this award and I am deeply grateful to the Hereditary Disease Foundation and to the Gehry family for their support of research that seeks to improve the lives of people with hereditary diseases such as Huntington’s disease. The award is a testament to the tireless efforts of the UCL HD Centre team and our collaborators as we seek to lead world-class research from bench to bedside. Every year we are getting closer to identifying treatments that could slow down the disease process, and ways to prevent or delay disease onset in HD gene carriers,”

Professor Michael Hanna, Director of the UCL Institute of Neurology, said: “Congratulations to Sarah on this major achievement. We are proud to host the UCL HD Centre at the UCL Institute of Neurology, Queen Square. It is the largest and most productive clinically-focused HD research group in the UK, and is at the forefront of neurodegenerative disease research and has real potential to transform people’s lives.”

Professor Nancy Wexler, President of the Hereditary Disease Foundation, said, “We are thrilled to present the Leslie Gehry Brenner Prize to Sarah Tabrizi. Professor Tabrizi has channelled her passion for scientific research into discovering ways to prevent or reverse Huntington’s Disease.  We thank her and her superb global team for their extraordinary work.”

12th September, 2017 - UCL HD Centre wins two prestigious ‘Insight of the Year’ awards

 

Professor Sarah Tabrizi

Huge congratulations to the Huntington Disease Centre, UCL Institute of Neurology, which has won two ‘Insight of the Year’ awards from the Huntington Study Group.

The HD Centre was recognised for two groundbreaking studies that were published separately by Lancet Neurology in June 2017.

The first study identified a blood test that can predict the onset and progression of Huntington’s disease (HD). Two of the authors, Lauren Byrne and Dr Ed Wild, commented that the blood test, which measures a neurofilament light protein released from damaged brain cells, could help them design and run clinical trials of new HD treatments.

Lauren Byrne, Nancy Wexler (who discovered the HD gene) and Dr Ed Wild

The second ‘Insight’ award was for a study which identified a genetic modifier associated with HD progression. The research team, which included Dr Davina Hensman-Moss and Professor Sarah Tabrizi, said that targeting this gene could lead to the development of life-extending treatments for HD patients.

Dr Davina Hensman-Moss

Upon publication, both studies received praise from international HD experts and significant media coverage.

The Huntington Study Group (HSG) is a US-based research organisation for clinical researchers, medical professionals, advocacy groups and others affected by HD. Its ‘Insight of the Year’ awards are judged by its journal editorial board and other researchers, who select the most influential paper in four categories.

Professor Ray Dorsey, Chair of HSG, stated: “HDInsights is pleased to recognize both these papers from UCL researchers and their colleagues. Together they bring us closer to developing treatments that make a difference for families affected by Huntington disease.”

Dr Wild commented that, as the HSG gives only four ‘Insight’ awards annually, it is a remarkable achievement for the HD Centre to win two in one year.

Commenting on the double win, Prof Tabrizi said: “This international recognition of our research is a testament to UCL’s vision in supporting the establishment of UCL HD Centre, and our mission of leading world-class research from bench to bedside that we hope will change the future for families affected by Huntington’s disease and other neurodegenerative disorders.”

The UCL HD Centre opened in March 2017 as a UCL IoN Research Centre. It is directed by Professor Tabrizi and co-directed by Professor Gill Bates. The Centre brings together expertise from many disciplines, making it uniquely placed to translate mechanistic insights into first-in-human studies in HD.

Huntington’s disease is a fatal genetic neurological disease; it is currently incurable and there are no existing effective treatments to slow its progression. Around 10,000 people in the UK have HD, and a further 25,000 are at risk of the disease.

Related

19th June, 2017 - Genetic modifier of Huntington’s disease progression identified

A team led by UCL and Cardiff University researchers has developed a novel measure of disease progression for Huntington’s disease, which enabled them to identify a genetic modifier associated with how rapidly the disease progresses.

“We’ve identified a gene that could be a target for treating Huntington’s disease. While there’s currently no cure for the disease, we’re hopeful that our finding could be a step towards life-extending treatments,” said Dr Davina Hensman Moss (UCL Huntington’s Disease Centre, UCL Institute of Neurology), one of the lead authors of the Lancet Neurology study.

Huntington’s disease (HD) is a fatal neurological disease caused by a genetic mutation. Larger mutations are linked to rapidly progressing disease, but that does not account for all aspects of disease progression. Understanding factors which change the rate of disease progression can help direct drug development and therapies.

The research team used the high quality phenotypic data from the intensively studied TRACK-HD cohort of people with the HD gene mutation.  They established that different symptoms of disease progress in parallel, so they were able to combine the data from 24 cognitive, motor and MRI brain imaging variables to generate their progression score for genetic analysis.

They then looked for areas of the genome associated with their progression measure, and found a significant result in their sample of 216 people, which they then validated in a larger sample of 1773 people from a separate cohort, the European Huntington’s Disease Network (EHDN) REGISTRY study.

 

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Figure: The genome wide significant hit on chromosome 5 in the region of MSH3 is seen in this Manhattan plot of the meta-analysis of the TRACK-HD and REGISTRY progression analyses. Green line: 5×10-8.

 

The genetic signal is likely to be driven by the gene MSH3, a DNA repair gene which has been linked to changes in size of the HD mutation. The researchers identified that a variation in MSH3 encodes an amino acid change in the gene. MSH3 has been previously been extensively implicated in the pathogenesis of HD in both mouse and cell studies. The group’s findings may also be relevant to other diseases caused by repeats in the DNA, including some spinocerebellar ataxias.

Dr Hensman Moss said: “The gene variant we pinpointed is a common variant that doesn’t cause problems in people without HD, so hopefully it could be targeted for HD treatments without causing other problems.”

Professor Lesley Jones (Cardiff University), who co-led the study, said: “The strength of our finding implies that the variant we identified has a very large effect on HD, or that the new progression measure we developed is a much better measure of the relevant aspects of the disease, or most likely, both.” 

The researchers say their study demonstrates the value of getting high quality data about the people with a disease when doing genetic studies.

Professor Sarah Tabrizi (UCL Huntington’s Disease Centre), who co-led the study said: “This is an example of reverse translation: these novel findings we observed in people with HD support many years of basic laboratory work in cells and mice.  Now we know that MSH3 is critical in the progression of HD in patients, we can focus our attention on it and how this finding may be harnessed to develop new therapies that slow disease progression.”

The study was funded by the European Commission FP7 NeurOmics project, CHDI Foundation, the Medical Research Council, the Brain Research Trust, and the Guarantors of Brain.

7th June, 2017 - Blood test can predict onset and track progression of Huntington’s disease

A team led by Dr Ed Wild of UCL Huntington’s Disease Centre has identified the first blood test that can predict the onset and progression of Huntington’s disease.
 

The findings, published today in Lancet Neurology, should help test new treatments for the genetic brain disorder.
 

“This is the first time a potential blood biomarker has been identified to track Huntington’s disease so strongly,” said Dr Wild.
 

The test measures the neurofilament light chain (neurofilament), a protein released from damaged brain cells, which hasn’t been studied in the blood of Huntington’s disease (HD) patients before.
 

The team measured neurofilament levels in blood samples from the TRACK-HD study, an international project that followed 366 volunteers for three years. They found that levels of the brain protein were increased throughout the course of HD – even in carriers of the HD genetic mutation who were many years from showing symptoms of the disease.
 

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In the group who had no symptoms at the start of the study, the level of neurofilament predicted subsequent disease onset, as volunteers with high neurofilament levels in the blood at the start were more likely to develop symptoms in the following three years.
 

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“We have been trying to identify blood biomarkers to help track the progression of HD for well over a decade, and this is the best candidate that we have seen so far,” said Dr Wild. “Neurofilament has the potential to serve as a speedometer in Huntington’s disease, since a single blood test reflects how quickly the brain is changing. That could be very helpful right now as we are testing a new generation of so-called ‘gene silencing’ drugs that we hope will put the brakes on the condition. Measuring neurofilament levels could help us figure out whether those brakes are working.”
 

The researchers caution that the test is not expected to be immediately helpful for individual patients. “This is the first time neurofilament has been measured in blood, so much more work is needed to understand the potential and limitations of this test,” said Lauren Byrne, the study’s first author. “In the future, if drugs to slow HD become available, it may well be used to guide treatment decisions. For now, this test is most promising as a much-needed tool to help us design and run clinical trials of new drugs.
 

Dr Robert Pacifici, chief scientific officer of CHDI Foundation, a US non-profit Huntington’s disease research foundation, welcomed the development. “I can see neurofilament becoming a valuable tool to assess neuroprotection in clinical trials so that we can more quickly figure out whether new drugs are doing what we need them to. As a drug hunter, this is great news.”
 

Link to the full article and a commentary written by eminent HD researcher Prof Chris Ross (Johns Hopkins University).