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

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).

2nd March, 2017 - The UCL Huntington’s Disease Centre opens

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We are delighted to announce that the UCL Huntington’s Disease Centre, UCL Institute of Neurology, was officially opened on 1 March by UCL President and Provost Professor Michael Arthur.

Directed by Professor Sarah Tabrizi FMedSci and co-directed by Professor Gill Bates FRS, and bringing together expertise from many disciplines, the Centre is uniquely placed worldwide to translate mechanistic insights into first-in-human studies in HD.

The Centre will answer important questions of early diagnosis and mechanistic understanding which will help refine and redefine disease, preparing for precision medicine and driving therapeutic innovation.

Professors Tabrizi and Bates, who together are world leaders in bench-to-bedside Huntington’s disease (HD) research, will be working alongside Dr Ed Wild, a new Principal Investigator in the Centre.

Tabrizi and Bates have already made considerable contributions to every aspect of HD research, from gene identification, underlying molecular mechanisms, animal modelling, therapeutic target validation and experimental medicine. Their basic science research programmes are focussing on the identification and validation of therapeutic targets that are proximal to the HD mutation and one of the first screening assays to be established by the ARUK DDI at UCL will be based on their work.

“I am delighted to have been recruited to UCL to establish the HD Centre with Prof Tabrizi. Our combined research programmes underpin all aspects of the translational pipeline, and will enable the HD Centre to make a significant contribution to the development of treatments for HD”.  Professor Gill Bates, Co-Director of UCL Huntington’s Disease Centre

It is this translational research approach that will underpin the Centre’s overarching aim to develop and test effective therapies for HD, and to set the ground work to eventually prevent the clinical disease occurring completely

Linking with the Leonard Wolfson Experimental Neurology Centre (LWENC), the Centre is able to conduct first in man and proof-of-concept studies in patients prior to initiating larger phase 2 and 3 clinical trials, including their novel huntingtin-lowering trials.

“The creation of the UCL HD centre comes at a key time in HD research with potential disease modifying gene silencing trials in phase 1 with more in the pipeline. This bench-to-bedside research approach will underpin our aim to develop and test effective therapies for HD that prevent the clinical disease occurring. We believe we are pivotally placed to be able to translate effective therapies to patients affected by this terrible disease”. Professor Sarah Tabrizi, Director of UCL Huntington’s Disease Centre

“The lessons taken from the Centre’s impressive work will also help our wider understanding of neurological diseases and dementia, and link with the aims of the Institute of Neurology and the UCL led UK Dementia Research Institute: to transform the pace and power of research to find treatments for neurological diseases”. Professor Mike Hanna, Director of the UCL Institute of Neurology

Further information:

Image: Provost Michael Arthur and HD family member Amanda Staveley

 

28th February, 2017 - Professor Flaviano Giorgini appointed as Honorary Professor of University College London in the Institute of Neurology and UCL Huntington’s Disease Centre

Professor Flaviano Giorgini has been named an Honorary Professor of University College London in the Institute of Neurology and UCL Huntington’s Disease Centre. The appointment – which will be in effect for 5 years – builds upon joint MRC-funded studies with Professor Gillian Bates and collaborative work with Professor Sarah Tabrizi and Dr Edward Wild.

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Professor Flaviano Giorgini

Giorgini is Professor of Neurogenetics at the Department of Genetics, University of Leicester, and his research is focused upon understanding the molecular mechanisms underlying neurodegenerative disorders such as HD, with the goal of using this information to inform novel therapeutic strategies. His current HD-related work explores the contributions of the kynurenine pathway, mitochondrial dysfunction, and vesicle trafficking alterations to disease pathogenesis. He is also interested in the role of the Parkinsonian protein DJ-1 in neurodegeneration and alpha-synuclein mediated vesicle trafficking defects in Parkinson’s disease. He is chair of the Science and Bioethics Advisory Committee of the European HD Network and a member of Parkinson’s UK Grant Assessment Panel.

18th November, 2016 - The UCL Huntington’s Disease Centre

The UCL Huntington’s Disease Centre

A Huntington’s Disease Centre has been established at University College London and will officially open in March 2017. It is directed by Professor Sarah Tabrizi and co-directed by Professor Gillian Bates, who has recently been recruited to UCL. Professor Tabrizi and Professor Bates will be working alongside Dr Ed Wild, a Principal Investigator in the Centre with a research group supported by an MRC Clinician Scientist Fellowship and CHDI Foundation.

The new UCL Huntington’s Disease Centre is uniquely placed world-wide to translate mechanistic insights to ‘first in human’ studies, led by Professors Tabrizi and Bates who together are world leaders in bench-to-bedside HD research. Within a single purpose-built facility, the Centre will bring together expertise from many disciplines, combining sophisticated cell-based systems, animal work, translational research and clinical trials. The Centre will answer important questions of early diagnosis and mechanistic understanding which will help refine and redefine disease, preparing for precision medicine and driving therapeutic innovation. Linking with the Leonard Wolfson Experimental Neurology Centre (LWENC), the HD Centre is able to conduct small proof-of-concept studies in patients prior to initiating larger phase 2 and 3 clinical trials, including novel huntingtin-lowering trials. In this way we anticipate that our unparalleled team of experts will spearhead a new era of disease-modifying therapeutics for HD.

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The Huntington’s Disease Research Centre logo depicts a human figure composed from two intertwining strands, evoking the DNA we inherit from each parent. The figure is leaping forwards – a reference to the dance-like involuntary movements seen in people with Huntington’s disease – into a hope-filled future free from the disease.