New hope in fight against Huntington's disease

University of Leicester-led research uncovers potential new approaches for tackling devastating disorder

2011-01-11

(Press-News.org) Hope for new ways of treating devastating neurodegenerative disorders such as Huntington's disease has been raised by a trans-Atlantic team of researchers thanks to the use of cutting-edge genetic techniques.

Led by the University of Leicester, scientists from the University of Lisbon (led by Dr Tiago Outeiro) and University of California at San Francisco (led by Dr Paul Muchowski) collaborated to generate novel approaches for tackling the diseases. Their work, funded by the Medical Research Council, is published in The Journal of Biological Chemistry.

At Leicester, working simply with baker's yeast, a team of biological scientists examined aspects of Huntington's disease. These yeast are extremely well-characterised and have powerful and facile genetics which allow researchers to rapidly interrogate this system at a genome-wide level. Research in recent years has found that baker's yeast can be used to study mechanisms underlying disease pathology, and this simple organism has been used to identify several promising candidate drug targets for neurodegenerative disorders, including Huntington's disease.

Flaviano Giorgini, lead author of the research paper at the University of Leicester, said: "My research group is interested in using genetics and genomics approaches to better understand the fatal neurodegenerative disorders of Huntington's disease and Parkinson's disease.

"By clarifying the genes and cellular pathways involved in these diseases we hope to identify novel strategies for treatment and therapy of these disorders. In our work we use simple, yet powerful genetic organisms such as baker's yeast and fruit flies to model aspects of these devastating diseases.

"In the current study we have used a novel functional genomics profiling approach to identify genes which can protect these simple organisms from disease symptoms. We then used computational approaches to uncover a network of interactions amongst these genes, which has shed light on the mechanisms underlying this disorder."

Using the approach above, the scientists found that many of the protective genes are involved in translation – a cellular process in which messenger RNA (mRNA) is decoded by the ribosome to produce specific proteins. This is particularly intriguing as this process has not been implicated in Huntington's disease in the past.

This is important because recent work indicates that pharmacological modulation of translation may represent a promising avenue for treatment of Parkinson's disease. Therefore, this new research strongly dovetails with these observations and suggests that similar drug treatment may be beneficial in Huntington's disease.

Dr Giorgini, of the Department of Genetics, said: "Our research has taken advantage of cutting edge genomics approaches using a simple model organism to identify a novel area for potential therapeutic intervention for Huntington's disease.

"If our findings are validated by further studies, it might suggest a novel therapeutic approach for this devastating disorder - which is critical as currently there are no treatments for onset or progression of symptoms."

INFORMATION:

NOTES TO EDITORS

For more information, please contact:

Flaviano Giorgini, PhD
Lecturer in Mammalian Genetics
Department of Genetics
University of Leicester
Leicester LE1 7RH, UK
Phone: 44 (0)116 252 3485
E-mail: fg36@le.ac.uk
Web: http://www.le.ac.uk/ge/fg36/

Citation:

Functional Gene Expression Profiling in Yeast Implicates Translational Dysfunction in Mutant Huntington Toxicity

The Journal of Biological Chemistry, Vol. 286, Issue 1, 410-419, JANUARY 7, 2011

Eran Tauber; Leonor Miller-Fleming; Robert P. Mason; Jannine Clapp; Nicola J. Butler; Flaviano Giorgini University of Leicester

Leonor Miller-Fleming; Tiago F. Outeiro
Universidade de Lisboa

Wanda Kwan; Paul J. Muchowski
University of California at San Francisco

ARTICLE #10.1074/jbc.M110.101527

ABOUT THE MRC

For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk

ABOUT HUNTINGTON'S DISEASE

Huntington's disease is an inherited disease of the brain

The disease damages the nerve cells in the brain, causing deterioration and gradual loss of function of areas of the brain. This affects movement, cognition (perception, awareness, thinking, judgement) and behaviour.

Early symptoms such as personality changes, mood swings and bizarre behaviour are often overlooked at first and attributed to something else.

Huntington's disease was originally called Huntington's chorea, after the Greek word for dancing, as the associated involuntary movements can look like jerky dancing.

Both men and women with a family history of Huntington's can inherit the disease and symptoms usually start to show in adulthood.

Juvenile (children's) Huntington's disease develops before the age of 20 years. Only 5-10% of people with Huntington's develop the condition at a very young age, and the pattern of features may be different.

UK studies have found that approximately 6-7 people per 100,000 of the population are affected by Huntington's disease. However, it is likely that the true figure is much higher.

There is no cure for Huntington's disease and its progress cannot be reversed or slowed down.

Medication can be used to manage some of the symptoms, and therapies (such as speech and language therapy and occupational therapy) can help with communication and day-to-day living

Surce: NHS Choices (http://www.nhs.uk/conditions/Huntingtons-disease/Pages/Introduction.aspx)

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New hope in fight against Huntington's disease

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