By Megan Rauscher
NEW YORK (Reuters Health) – Researchers have shown in mouse models of Parkinson’s disease that blocking calcium channels in adult dopaminergic neurons coaxes them back into a more juvenile state, thereby protecting them against disease progression.
These findings point to a potential new therapeutic strategy to slow or halt the progression of Parkinson’s disease, according to the team’s report in the journal Nature published online June 10.
"We made three key observations," Dr. D. James Surmeier of Northwestern University, Chicago, told Reuters Health. The first observation, he explained, was that dopaminergic neurons that die in Parkinson’s disease change in a way as they age that makes them more vulnerable to toxins and stress.
"Specifically, we found that these neurons increase their reliance upon calcium channels to drive their basal pacemaking activity. Calcium ions are essential for normal cellular function but in excess can kill," Dr. Surmeier explained.
The second observation was that blocking these calcium channels in adult dopaminergic neurons causes them to revert to a juvenile form of pacemaking activity that does not rely upon calcium. "After this ‘rejuvenation’, neurons became much more resistant to toxins and stress," Dr. Surmeier told Reuters Health.
The third observation was that the blockade of these calcium channels and the rejuvenation could be accomplished with the dihydropyridine isradipine — a drug that has been used for decades to treat hypertension.
In essence, Dr. Surmeier said, "We have identified a drug that you could take with your coffee in the morning that might slow or stop the progression of Parkinson’s disease."
Data from a recent retrospective study of hypertensive patients suggests that dihydropyridine use may lower the incidence of Parkinson’s by 30% to 50%, the authors note in their report.
"Because isradipine is approved for human use, the path between where we are now and clinical practice is potentially very short," Dr. Surmeier said. The next step is a phase III clinical trial to determine whether isradipine slows the progression of the disease in humans. A proposal to conduct this trial will be submitted this fall, Dr. Surmeier said.