Featured Research

from universities, journals, and other organizations

Toxic protein build-up in blood shines light on fatal brain disease

Date:
September 17, 2012
Source:
University College London
Summary:
A new light-based technique for measuring levels of the toxic protein that causes Huntington's disease (HD) has been used to demonstrate that the protein builds up gradually in blood cells. The findings shed light on how the protein causes damage in the brain, and could be useful for monitoring the progression of HD, or testing new drugs aimed at suppressing production of the harmful protein.

This image shows TR-FRET and Huntington protein.
Credit: UCL Press Office

A new light-based technique for measuring levels of the toxic protein that causes Huntington's disease (HD) has been used to demonstrate that the protein builds up gradually in blood cells. Published September 17 in the Journal of Clinical Investigation, the findings shed light on how the protein causes damage in the brain, and could be useful for monitoring the progression of HD, or testing new drugs aimed at suppressing production of the harmful protein.

HD is a fatal, incurable, genetic neurological disease that usually develops in adulthood and causes abnormal involuntary movements, psychiatric symptoms and dementia. It is caused by a genetic mutation that results in the production of a harmful protein, called mutant huntingtin.

The research team, led by Professor Sarah Tabrizi of the UCL Institute of Neurology, was made up of scientists from UCL, the Novartis Institutes for Biomedical Research and King's College London. They used a new, ultra-sensitive test to measure how much of the harmful protein and its normal counterpart are found in blood cells from HD patients at different stages of the disease. The test, called TR-FRET, uses pairs of antibodies that stick to huntingtin molecules to absorb and emit light of different colours. This enables very tiny amounts of huntingtin to be detected with great accuracy.

The researchers found that levels of the harmful mutant huntingtin protein built up gradually over the course of the disease, from before the patients show any symptoms onwards. HD causes the brain to shrink more rapidly than normal, as measured using MRI scans. Surprisingly, the amount of mutant protein in white blood cells corresponded to the rate of brain shrinkage. This is the first time a blood test has been able to predict brain shrinkage in a neurodegenerative disease. Levels of the normal huntingtin protein, on the other hand, stayed constant throughout the disease.

The team went on to demonstrate that small fragments of the most toxic part of the protein were slowly building-up in the white blood cells -- the first time this has been demonstrated in cells from human HD patients. If a similar process occurs in brain cells such as neurons, this finding may help explain how the damage gradually accumulates, eventually causing symptoms of HD.

This build-up of the mutant protein in the white blood cells of the immune system may also explain previous findings by Professor Tabrizi's team which showed that the immune system is hyperactive in HD.

"Measuring levels of the mutant protein using TR-FRET is a useful new tool in the fight against HD," said Professor Tabrizi. "We can now accurately study the most toxic form of the huntingtin protein in easily obtained blood samples from real patients. The fact that mutant huntingtin levels correlate with brain atrophy tells us we're dealing with something that's relevant to the process of brain degeneration in HD."

The new technique could also be an asset for forthcoming clinical trials of 'gene silencing' drugs that aim to suppress production of the toxic protein in the brain.

"Gene silencing drugs are very promising, but have significant potential for causing side effects, so we really need to know they're doing their job of lowering huntingtin levels," continued Professor Tabrizi. "This TR-FRET technique offers a way of showing that in real human samples, and we hope that it will help speed up the process of developing drugs that work to slow down this terrible disease."


Story Source:

The above story is based on materials provided by University College London. Note: Materials may be edited for content and length.


Journal Reference:

  1. Andreas Weiss, Ulrike Trδger, Edward J. Wild, Stephan Grueninger, Ruth Farmer, Christian Landles, Rachael I. Scahill, Nayana Lahiri, Salman Haider, Douglas Macdonald, Chris Frost, Gillian P. Bates, Graeme Bilbe, Rainer Kuhn, Ralph Andre and Sarah J. Tabrizi. Mutant huntingtin fragmentation in immune cells tracks Huntington’s disease progression. Journal of Clinical Investigation, 2012 DOI: 10.1172/JCI64565

Cite This Page:

University College London. "Toxic protein build-up in blood shines light on fatal brain disease." ScienceDaily. ScienceDaily, 17 September 2012. <www.sciencedaily.com/releases/2012/09/120917123933.htm>.
University College London. (2012, September 17). Toxic protein build-up in blood shines light on fatal brain disease. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2012/09/120917123933.htm
University College London. "Toxic protein build-up in blood shines light on fatal brain disease." ScienceDaily. www.sciencedaily.com/releases/2012/09/120917123933.htm (accessed July 25, 2014).

Share This




More Mind & Brain News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

University Quiz Implies Atheists Are Smarter Than Christians

University Quiz Implies Atheists Are Smarter Than Christians

Newsy (July 25, 2014) — An online quiz from a required course at Ohio State is making waves for suggesting atheists are inherently smarter than Christians. Video provided by Newsy
Powered by NewsLook.com
Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

AFP (July 24, 2014) — A so-called drugs rehab 'clinic' is closed down in Pakistan after police find scores of ‘patients’ chained up alleging serial abuse. Duration 03:05 Video provided by AFP
Powered by NewsLook.com
New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) — The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Can Watching TV Make You Feel Like A Failure?

Can Watching TV Make You Feel Like A Failure?

Newsy (July 24, 2014) — A study by German researchers claims watching TV while you're stressed out can make you feel guilty and like a failure. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins