A commonly used blood-pressure drug may prevent the onset of Parkinson's disease, according to a new study in mice.
Human trials of isradipine (or DynaCirc) - which is prescribed for hypertension and stroke - are now planned.
Over time, Parkinson's patients lose a set of brain cells that produce the crucial signalling chemical dopamine - and these cells do not regenerate. Without enough dopamine, people cannot control their body movements and ultimately develop severe neurological problems, including dementia.
Scientists have struggled to understand why the dopamine-producing brain cells start dying, but ageing plays a strong role.
James Surmeier at Northwestern University in Illinois, US, and colleagues found that in young mice these cells use sodium channels to send signals, but in older mice they rely more on a certain kind of calcium channel.
This can prove deadly for a neuron because calcium accumulates inside the cell, eventually triggering a complete breakdown.
Surmeier wondered whether he could reverse the switch to calcium channels: "The cells had put their old childhood tools in the closet. The question was, if we stopped them from behaving like adults, would they go into the closet and get them out again?"
He believed that isradipine, which blocks the same type of calcium channel, could help these cells revert to a younger state. His experiments in a lab dish showed that exposing cells to the drug caused them to increase their use of sodium-based signalling.
The team then implanted a time-release capsule of the drug beneath the skin of mice that had just reached adulthood. This implant released a daily dose of isradipine that, if scaled up for humans, would correspond to roughly 10 times the dose for a person with hypertension, but less than the amount given to treat stroke.
A week after starting this regimen, the mice also began receiving bi-weekly injections of a chemical called MPTP that poisons the brain's dopamine-producing cells. The death of these cells simulates Parkinson's in mice.
Five weeks later, the mice receiving isradipine showed no outward signs of disease. "They looked perfectly normal," Surmeier says. When researchers tested the animals' ability to grip a wire mesh, the mice held on just as well as their control counterparts that had not received MPTP.
By comparison, the mice that received MPTP but not isradipine fumbled around showing symptoms of Parkinson's. "They didn't move very readily and had to spread their feet out when they walk for extra balance," says Surmeier.
His team plans to see whether isradipine can help mice that have already developed Parkinson's disease symptoms.
Epidemiological evidence supports Surmeier's findings. A survey of people taking isradipine for hypertension found that they had a 30% to 50% reduced risk of Parkinson's disease, he says.
His team has already recruited a small group of Parkinson's patients to see if they can tolerate high doses of isradipine, which can cause side-effects such as headaches and dizziness. They are also hoping to conduct a larger trial of the drug to find out if it can significantly slow the disease's progression.
"There are a lot of different approaches [to developing a cure], and it's important that they all be tried," says Linda Herman, a New York-based patient-advocate and member of the Parkinson's Pipeline Project.
But Herman cautions that people should reserve their enthusiasm for isradipine until researchers show the drug has an effect on Parkinson's in humans.
Many patients with Parkinson's currently take a drug called L-dopa, which gets converted to dopamine in the brain. But patients become less responsive to the drug over time and their symptoms worsen.
Journal reference: Nature (DOI: 10.1038/nature05865)
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