A new genetic progression measure for Huntington's disease offers hope

August 10, 2017
A new genetic progression measure for Huntington’s disease offers hope
Credit: Shutterstock

Partly supported through the EU NEUROMICS project, researchers have identified a novel measure of disease progression for Huntington's disease that could help slow down the disease and better target future therapies.

Huntington's disease (HD), a rare degenerative inherited gene, affects up to approximately one in 10 000 people in Europe. Whilst HD remains a fatal neurological disease which develops at a gradual and relentless rate with an average duration of 15-20 years, a team of researchers led by Cardiff University and University College London (UCL) have identified a novel measure of the disease's progression to help better understand the disease and its development.

'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,' describes Professor Lesley Jones (Cardiff University), who co-led the study published in The Lancet.

Whilst larger mutations are linked to the rapidly progressing disease, not all factors behind the disease's progression are known. As a result, using high quality phenotypic data on people with the HD gene mutation, the team established that different symptoms of disease progress in parallel which meant they could combine and compare data from cognitive, motor and MRI brain imaging variables to deliver a progression score for genetic analysis.

They also 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 1 773 people from a separate cohort, the European Huntington's Disease Network (EHDN) REGISTRY study.

'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 of UCL's Huntington's Disease Centre, a lead author of the study.

The genetic signal in question 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.

HD's exact pathway remains unclear but we know that the striatum, a structure of the basal ganglia located in the central region of the brain - responsible for planning and controlling movements but also other cognitive (thinking) processes - is the part of the brain most affected by HD. Loss of cortex (grey matter in the outermost layers of the brain) occurs during disease progression which contributes to the worsening of the cognitive function. Moreover, HD usually develops in adulthood and causes abnormal involuntary movements, psychiatric symptoms and dementia. Each child of a carrier of the mutation has a 50 % chance of inheriting the disease.

Nevertheless these findings will undoubtedly help better target future HD studies and treatments against the , '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 ,' explains Professor Sarah Tabrizi, another co-author of the study.

The EU-funded NEUROMICS project, which supported the research leading to the article in 'The Lancet', uses the most sophisticated -Omics technologies to revolutionise diagnostics and to develop pathomechanism-based treatment for ten major Neurodegenerative (ND) and neuromuscular (NM) diseases, which includes Huntington's.

Explore further: Genetic modifier for Huntington's disease progression identified

More information: Project website: rd-neuromics.eu/

Related Stories

Genetic modifier for Huntington's disease progression identified

June 20, 2017
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 ...

Researchers track Huntington's disease progression using PET scans

August 29, 2013
Investigators at The Feinstein Institute for Medical Research have discovered a new way to measure the progression of Huntington's disease, using positron emission tomography (PET) to scan the brains of carriers of the gene. ...

Blood test can predict onset and track progression of Huntington's disease

June 7, 2017
The first blood test that can predict the onset and progression of Huntington's disease has been identified by a UCL-led study.

Huntington's disease linked to dysfunction of brain structure

December 21, 2016
Northwestern Medicine scientists identified a link between Huntington's disease and dysfunction of the subthalamic nucleus, a component of the basal ganglia, a group of brain structures critical for movement and impulse control.

New discovery toward developing Huntington's disease treatments before symptoms appear

February 22, 2017
Early warning signs of Huntington's disease have been uncovered in a sheep carrying the human HD mutation, leading the way for new insight into this devastating illness, a new study in Scientific Reports has found.

Drug reduces brain changes, motor deficits associated with Huntington's disease

November 26, 2013
A drug that acts like a growth-promoting protein in the brain reduces degeneration and motor deficits associated with Huntington's disease in two mouse models of the disorder, according to a study appearing November 27 in ...

Recommended for you

Investigating patterns of degeneration in Alzheimer's disease

November 17, 2017
Alzheimer's disease (AD) is known to cause memory loss and cognitive decline, but other functions of the brain can remain intact. The reasons cells in some brain regions degenerate while others are protected is largely unknown. ...

Brain activity buffers against worsening anxiety

November 17, 2017
Boosting activity in brain areas related to thinking and problem-solving may also buffer against worsening anxiety, suggests a new study by Duke University researchers.

Study may point to new treatment approach for ASD

November 17, 2017
Using sophisticated genome mining and gene manipulation techniques, researchers at Vanderbilt University Medical Center (VUMC) have solved a mystery that could lead to a new treatment approach for autism spectrum disorder ...

Neuroscience research provides evidence the brain is strobing, not constant

November 17, 2017
It's not just our eyes that play tricks on us, but our ears. That's the finding of a landmark Australian-Italian collaboration that provides new evidence that oscillations, or 'strobes', are a general feature of human perception.

Paraplegic rats walk and regain feeling after stem cell treatment

November 16, 2017
Engineered tissue containing human stem cells has allowed paraplegic rats to walk independently and regain sensory perception. The implanted rats also show some degree of healing in their spinal cords. The research, published ...

Neuroscientists find chronic stress skews decisions toward higher-risk options

November 16, 2017
Making decisions is not always easy, especially when choosing between two options that have both positive and negative elements, such as deciding between a job with a high salary but long hours, and a lower-paying job that ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.