The drug isradipine, commonly used to treat blood pressure and stroke, could one day help to slow down or even stop the progression of Parkinson's disease, according to new research by US scientists.

The study is published in the early online edition of the journal Nature.

Scientists at Northwestern University in Chicago, Illinois, US, managed to show that isradipine slowed the progression of Parkinson's in mice, and are now planning clinical trials on humans.

Parkinson's occurs when dopamine cells in the brain die off. Dopamine is a chemical messenger or neurotransmitter that helps the brain to control movement. When the cells that release it die off, movement becomes harder to control, and eventually the affected person loses the ability to walk, talk and pick things up. There is no cure as yet for the disease.

About 1 million Americans live with Parkinson's; it is the second most common degenerative brain disease in the US (the first being Alzheimer's). People over 60 years old are at most risk, and risk increases with age.

The researchers at Northwestern University discovered that isradipine rejuvenates worn out dopamine cells.

Dr D. James Surmeier, who is Nathan Smith Davis Professor and chair of physiology at Northwestern University's Feinberg School of Medicine, and also head of the Morris K. Udall Center of Excellence for Parkinson's Disease Research at Northwestern, led the study. Sumrmeier has been researching Parkinson's for 20 years. He said their hope for this discovery was that:

"This drug will protect dopamine neurons, so that if you began taking it early enough, you won't get Parkinson's disease, even if you were at risk."

"There has not been a major advance in the pharmacological management of Parkinson's disease for 30 years," he said, explaining why this study is exciting.

"It would be like taking a baby aspirin everyday to protect your heart," he added.

As well as delaying or avoiding onset, it is possible that isradipine may significantly benefit people who already have Parkinson's. Surmeier and colleagues found that by rejuvenating the dopamine cells, isradipine also stops them from being killed off by toxins, because younger cells are less vulnerable. At the moment people with Parkinson's are treated with a chemical, L-DOPA, that turns into dopamine in the brain. This helps to reduce many of the symptoms in the early stages, but as the disease progresses, higher and higher doses are needed to achieve the same effect. Also, L-DOPA has side-effects, including unwanted movement.

The researchers hope that their discovery means that if the death of dopamine cells can be slowed down or halted even, then treatment with isradipine could help people with Parkinson's stay on L-DOPA longer with good effect.

Surmeier said:

"If we could double or triple the therapeutic window for L-DOPA, it would be a huge advance."

The discovery was made when Surmeier decided to look into whether the vulnerability of dopamine cells might be explained by their electrical activity. Dopamine cells, like all neurons, send electrical signals to other neurons, using ions. Dopamine cells are like pacemakers, they send electical impulses on a regular basis all the time. Scientists had already discovered that brain cells use sodium ions to carry the electrical charge.

However, Surmeier and his team found that in the case of dopamine cells it was not sodium ions that were being used but calcium. Calcium ions are more troublesome and volatile, and they have to be closely controlled in the brain cell by either sequestering them or pumping them out. This takes more energy than the sodium based method.

The researchers thought that perhaps the continual stress on the dopamine cells could be the reason they are more vulnerable to toxins and die off more quickly as the person gets older.

Another chance discovery helped to bridge the link toward therapeutic applicaton. Working on a different study, Surmeier found that young dopamine cells worked quite differently to older ones.

When the dopamine cells are young, they use sodium ions, but these are gradually replaced with calcium as they age. The change to calcium is what starts them becoming vulnerable to toxins. So the researchers decided to try and stop the calcium getting into the dopamine cells to see if they reverted to using sodium.

They gave mice isradipine, and it blocked the calcium from getting into the dopamine cells. At first they just went quiet, but within a few hours they started their electrical pulses again, but using sodium ions instead of calcium ones. Surmeier said that:

"This lowers the cells' stress level and makes them much more resistant to any other insult that's going to come along down the road. They start acting like they're youngsters again."

Deputy Director of the National Institute of Neurological Disorders and Stroke (NINDS), Dr Walter J. Koroshetz said:

"This animal study suggests that calcium channel blockers, drugs currently used to reduce blood pressure, might someday be used to slow the steady progression of Parkinson's disease."

" 'Rejuvenation' protects neurons in mouse models of Parkinson's disease.
C. Savio Chan, Jaime N. Guzman, Ema Ilijic, Jeff N. Mercer, Caroline Rick, Tatiana Tkatch, Gloria E. Meredith and D. James Surmeier.
Nature advance online publication, 10 June 2007.
doi:10.1038/nature05865

Click here for Abstract.

Click here for resources on Parkinsons's Disease from The Parkinson's Web (US).

: Catharine Paddock
Writer: blog