Hyperactive immune system offers window to the brain in degenerative disease

July 14, 2008

Recent findings that a mutant gene can cause abnormal overactivity in the immune system could be significant in the search for treatments of Huntington's disease (HD) and other degenerative diseases such as Alzheimer's and Parkinson's, according to new research led by scientists at UCL (University College London) and published today in the Journal of Experimental Medicine.

HD is a fatal, incurable genetic neurological disease that usually develops in adulthood and causes abnormal involuntary movements, psychiatric symptoms and dementia. The new research by UCL scientists, working in close partnership with scientists from King's College London and institutions in Sweden, the USA and Canada, showed that abnormally high levels of molecules called cytokines - key to the body's immune response - were present in the blood of people carrying the HD gene many years before the onset of symptoms.

Finding these cytokine levels in the blood of HD gene carriers so long before they exhibit symptoms could be an important clue to some of the earliest changes caused by the HD gene. The combinations and levels of cytokines, easily measured from a blood test, could be useful markers to help measure the severity of HD, making it easier and quicker to test new drugs.

In addition, the team showed that white blood cells from HD patients were hyperactive, due to the presence of the abnormal HD gene inside the cell. This hyperactivity was also seen in microglia (the brain's immune cells) suggesting that abnormal immune activation could be one of the earliest abnormalities in HD, and that its signature in the blood could offer a glimpse into the effects of the disease in the brain. Abnormal immune activation could be a target for future treatments aimed at slowing down HD.

Dr Sarah Tabrizi, UCL Institute of Neurology, led the research. She said: "Finding increased cytokines in the blood was interesting, but the idea that the HD gene could be causing immune overactivity directly from within the white blood cells is important, because if the same thing is happening in the brain, cells that are there to protect neurons could be damaging them instead."

"It looks like we've unearthed a new early pathway by which the HD gene could cause damage, through abnormal overactivity of the immune system. What's more, this new pathway is quite easy to detect in the blood of patients, so we may have found a unique window from the blood into what the disease may be doing in the brain."

HD is currently incurable and no effective treatments exist to slow it down. It affects an estimated 4 to 10 per 100,000 people of European ancestry, and patients usually die within 20 years of the start of symptoms. The disease is caused by a single known genetic mutation, and each child of a carrier of the mutation has a 50 per cent chance of inheriting the disease.
-end-
Notes for Editors

1. Journalists seeking more information, or an interview with Dr Sarah Tabrizi, can contact Ruth Metcalfe in the UCL Media Relations Office on tel: +44 (0)20 7679 9739, mobile: +44 (0)7990 675 947, out of hours: +44 (0)7917 271 364, e-mail: r.metcalfe@ucl.ac.uk

2. The paper 'A novel pathogenetic pathway of immune activation detectable before clinical onset in Huntington's disease' is published online ahead of print today in the Journal of Experimental Medicine. For copies of the paper, please contact Media Relations using the details above.

3. The paper's authors are from Lund University, Sweden; UCL Institute of Neurology and UCL Department of Haemotology; University of British Columbia, Canada; University of Washington, US and King's College London.

4. Funding for this study was provided by CHDI (previously the High Q Foundation), Department of Health, the Medical Research Council (MRC), the Wellcome Trust, the Canadian Institutes for Health Research and the Huntington Society of Canada.

About UCL

Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. In the government's most recent Research Assessment Exercise, 59 UCL departments achieved top ratings of 5* and 5, indicating research quality of international excellence.

UCL is in the top ten world universities in the 2007 THES-QS World University Rankings, and the fourth-ranked UK university in the 2007 league table of the top 500 world universities produced by the Shanghai Jiao Tong University. UCL alumni include Marie Stopes, Jonathan Dimbleby, Lord Woolf, Alexander Graham Bell, and members of the band Coldplay. www.ucl.ac.uk

University College London

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.