Damage to D1 Neurons too Could Lead to Huntington’s Disease

by Gopalan on  March 20, 2008 at 2:23 PM Research News
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Damage to D1 Neurons too Could Lead to Huntington’s Disease
Australian researchers have found that damage to D1 neurons too could lead to the Huntington's disease. Thus far the focus had been on D2 neurons only.

In Huntington's disease, the first evidence of damage in the brain occurs in the part of the brain called the striatum; D1 and D2 neurons constitute 90% of neurons in the striatum.

It was previously thought that dopamine neurons, called D2 neurons, were responsible for the devastating symptoms seen in Huntington's disease but researchers at Melbourne's Howard Florey Institute have proven that loss of D1 neurons causes many of the disabling symptoms of the diseases.

Their discovery could be said to have opened up new treatment possibilities for the Huntington's.

Research leader John Drago, said now that the importance of D1 neurons in HD had been established, they could work towards therapies that focused on both D1 and D2 neurons.

"Currently there is no effective treatment for Huntington's disease and patients suffer from debilitating movement, memory, and psychiatric problems," he said.

Drago's discovery was made after he genetically engineered a mouse with damaged D1 neurons alone but which still developed the Huntington's.

While a mouse model that carries the human Huntington's disease gene already exists, Drago's mouse model is the first in the world to accurately mimic the death of the D1 neurons in the striatum.

"Despite the widespread death of D1 neurons, the mouse was healthy, apart from having HD symptoms," he said.

"This indicates that there is potential for a tremendous amount of natural repair occurring in the Huntington's diseased brain."

"Now the challenge is to thoroughly understand how this natural repair occurs so we can develop a therapy that encourages and enhances repair in human patients."

"Using the brain's own adult stem cells to naturally repair and prevent further damage is one treatment possibility that we eventually hope to explore," he said.

In addition to his research career, Drago is a neurologist at the St Vincent's Hospital Movement Disorder Clinic, where he treats patients with HD.

"It was the lack of effective treatments for patients that inspired me to undertake this research, so it is extremely satisfying to solve another piece of the Huntington's disease puzzle and work towards a cure for this progressive genetic disease," he said.

His research was published in the 26 February 2007 edition of the highly prestigious Proceedings of the National Academy of Sciences journal.

He was assisted by Dr Ilse Gantois, a postdoctoral researcher from Belgium, and the Florey's Neuroimaging group led by A/Prof Gary Egan, who undertook MRI scans of the mouse model to show its shrinking striatum as D1 neurons were dying and the response of the brain by making glial cells.

The Florey is taking two different approaches to its Huntington's disease research with this investigation and also Dr Anthony Hannan's environmental enrichment research, which has shown that physical and mental stimulation, can delay the onset of the disease and slow the progression of symptoms.

By tackling HD from two different angles, the Florey researchers hope to accelerate their discoveries into clinical outcomes to benefit HD patients.

The Howard Florey Institute is Australia's leading brain research centre. Its scientists undertake clinical and applied research that can be developed into treatments to combat brain disorders, and new medical practices. Their discoveries will improve the lives of those directly, and indirectly, affected by brain and mind disorders in Australia, and around the world. The Florey's research areas cover a variety of brain and mind disorders including Parkinson's disease, stroke, motor neuron disease, addiction, epilepsy, multiple sclerosis, autism and dementia.

Source: Medindia

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