New Treatment Possibilities For Fatal Genetic Disease

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

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.

Research leader, A/Prof 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.

A/Prof Drago’s discovery was made after he genetically engineered a mouse that displayed Huntington’s disease features by damaging only D1 neurons.

While a mouse model that carries the human Huntington's disease gene already exists, A/Prof 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,” A/Prof Drago 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, A/Prof 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.

A/Prof Drago’s research was published in the 26 February 2007 edition of the 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.