杏吧原创

A commonly used blood-pressure drug may prevent the onset of Parkinson鈥檚 disease, according to a new study in mice.

Human trials of isradipine (or DynaCirc) 鈥� which is prescribed for hypertension and stroke 鈥� are now planned.

Over time, Parkinson鈥檚 patients lose a set of brain cells that produce the crucial signalling chemical dopamine 鈥� and these cells do not regenerate. Without enough dopamine, people cannot control their body movements and ultimately develop severe neurological problems, including dementia.

杏吧原创s have struggled to understand why the dopamine-producing brain cells start dying, but ageing plays a strong role.

Calcium switch

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: 鈥淭he 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?鈥�

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.

Isradipine success

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鈥檚 dopamine-producing cells. The death of these cells simulates Parkinson鈥檚 in mice.

Five weeks later, the mice receiving isradipine showed no outward signs of disease. 鈥淭hey looked perfectly normal,鈥� Surmeier says. When researchers tested the animals鈥� 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鈥檚. 鈥淭hey didn鈥檛 move very readily and had to spread their feet out when they walk for extra balance,鈥� says Surmeier.

His team plans to see whether isradipine can help mice that have already developed Parkinson鈥檚 disease symptoms.

Trials planned

Epidemiological evidence supports Surmeier鈥檚 findings. A survey of people taking isradipine for hypertension found that they had a 30% to 50% reduced risk of Parkinson鈥檚 disease, he says.

His team has already recruited a small group of Parkinson鈥檚 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鈥檚 progression.

鈥淭here are a lot of different approaches [to developing a cure], and it鈥檚 important that they all be tried,鈥� says Linda Herman, a New York-based patient-advocate and member of the Parkinson鈥檚 Pipeline Project.

But Herman cautions that people should reserve their enthusiasm for isradipine until researchers show the drug has an effect on Parkinson鈥檚 in humans.

Many patients with Parkinson鈥檚 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.

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