Researchers at the University of British Columbia's Centre for Molecular Medicine and Therapeutics ( CMMT ) have provided ground-breaking evidence for a cure for Huntington disease in a mouse offering hope that this disease can be relieved in humans.

Published in Cell journal, Michael Hayden and colleagues discovered that by preventing the cleavage of the mutant huntingtin protein responsible for Huntington disease ( HD ) in a mouse model, the degenerative symptoms underlying the illness do not appear and the mouse displays normal brain function. This is the first time that a cure for Huntington disease in mice has been successfully achieved.

" Ten years ago, we discovered that huntingtin is cleaved by 'molecular scissors' which led to the hypothesis that cleavage of huntingtin may play a key role in causing Huntington disease", said Michael Hayden, at the Child and Family Research Institute's Centre for Molecular Medicine and Therapeutics.

Now a decade later, this hypothesis has resulted in a landmark discovery.

DiFiglia, at Massachusetts General Hospital, Harvard Medical School and one of the world's leading experts on Huntington disease. " Hayden and his team have shown in convincing fashion that many of the changes seen in HD patients can be erased in HD mice simply by engineering a mutation into the disease gene that prevents the protein from getting cleaved at a specific site."

To explore the role of cleavage, Hayden's team established an animal model of Huntington disease that replicated the key disease features seen in patients. A unique aspect of this particular animal model is that it embodied the human HD gene in exactly the same way seen in patients. This replication allowed researchers to examine the progression of HD symptoms including the inevitable cleavage of the mutant huntingtin protein.
In the study, researchers confirmed that the deadly cleavage is caused by a key enzyme called caspase-6. By blocking the action of this target, they showed that the mouse did not develop any symptoms of Huntington disease.

Hayden's team is now trying to test this model of prevention in a mouse using drug inhibitors and then ultimately in humans.

Huntington disease is a degenerative brain disease that affects one in every 10,000 Canadians.
The disease results from degeneration of neurons in certain areas of the brain causing uncontrolled movements, loss of intellectual faculties, and emotional disturbances. Currently, there is no treatment to delay or prevent Huntington disease in patients.

Source: University of British Columbia, 2006


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