In Parkinsonâ€™s Battle, Test Drug Brings Fresh Hope
A drug tested on lab mice slows and may even halt the progress of Parkinson’s, offering the brightest pharmacological hope in decades of rolling back this tragic disease, US researchers report.
Isradipine, already licensed for treatment for high blood pressure, rejuvenated ageing dopamine cells, the brain cells whose death causes Parkinson’s, they say.
The outcome among mice was so promising that the team now plan on conducting trials on human volunteers.
“Our hope is 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,” said lead researcher James Surmeier, professor of physiology at Northwestern University in Chicago.
“It would be like taking a baby aspirin every day to protect your heart.”
Parkinson’s is an incurable, degenerative disease of the central nervous system that causes uncontrollable shaking, along with impaired speech and movement. In approximately one third of cases it also results in dementia.
Estimates of its prevalence vary between 0.1 and 0.3 percent of the population, meaning that approximately one in 500 people contract the disease.
The cause is a loss of dopamine, a chemical messenger that helps direct movement. The substance is provided in a part of the brain called the substantia nigra.
Most pacemaking neurons use sodium ions to produce a regular electrical signal.
But the new research unexpectedly found that dopamine cells, when they reached adulthood, start to depend more and more on calcium ions.
This discovery is important, because calcium ions are far more troublesome to control than their placid sodium counterparts: the cell uses up lots of energy, either to round up and sequester the calcium or pump it out.
As a result, the dopamine cells become stressed on reaching their calcium-addicted adulthood and die prematurely.
Surmeier’s hunch was to try isradipine, a well-tolerated hypertension and stroke drug commercialized under the name of DynaCirc, which blocks the channels in the cell surface that admit calcium.
Tested on lab-dish cells and then on mice that had been genetically engineered to have Parkinson’s, the team found that within a few hours of being exposed to the drug, the neurons reverted to their youth-like state, of using sodium.
This lowered the cells’ stress level, making them less vulnerable to the toxins, still poorly understood, that kills them.
“They start acting like they’re youngsters again,” Northwestern quoted Surmeier as saying.
The study was published by Nature, the British science journal.
Surmeier voiced cautious hopes it could be the first treatment to prevent or slow the progression of this devastating disease.
The mainstay treatment for Parkinson’s is L-DOPA, a drug that the brain converts into dopamine.
At first, L-DOPA has a seemingly miraculous effective on symptoms. The problem, though, is that it becomes less and less effective as time wears on and the disease progresses. That forces doctors to raise the dose of this drug, which induces unwanted side-effects, including spastic, jerky movements.
So if isradipine can slow the death of dopamine neurons, the L-DOPA “honeymoon” could be significantly extended.
“If we could double or triple the therapeutic window for L-DOPA, it would be a huge advance,” said Surmeier. “There has not been a major advance in the pharmacological management of Parkinson’s in 30 years.”Filed under: Health