The researchers found that the drug tested in this study, a calcium channel blocking drug called isradipine, forces mouse dopamine neurons in a brain region called the substantia nigra to switch to a more youthful way of generating electrical signals. This reduced the neurons' vulnerability to toxins. The study appears in the June 28, 2007, issue of Nature.
"This animal study offers the hope that specific types of calcium channel blockers, relatives of those currently widely used to reduce blood pressure, might someday slow the steady progression of Parkinson’s disease,” says Walter J. Koroshetz, M.D., deputy director of the National Institute of Neurological Disorders and Stroke (NINDS), in a news release.
Isradipine and similar drugs are approved for use in people and, at doses needed to reduce blood pressure, they usually cause only minor side effects. However, the dose needed to prevent brain damage is likely to be higher than what is needed to reduce blood pressure. D. James Surmeier, Ph.D., and his colleagues at the Morris K. Udall Center of Excellence for Parkinson’s Disease Research at Northwestern University in Chicago, Illinois, are beginning a small study in people to learn whether higher-than-normal doses of isradipine are safe.
"One critically important issue is whether the doses needed to block calcium channels in the brain would cause dangerous drops in blood pressure, particularly in patients with Parkinson's disease who often have trouble with fainting due to low blood pressure," Dr. Koroshetz says.
Unlike most other calcium channel blockers that are used to treat hypertension, isradipine is effective at blocking the type of calcium channel expressed by the vulnerable dopamine neurons. This makes it particularly well suited for treating PD.
If isradipine proves safe and effective at reducing neuron damage in people, it might eventually be used to prevent PD in people at risk of the disease, in addition to treating the disease after it begins, Dr. Surmeier suggests.
Dr. Surmeier is now studying isradipine in animal models to learn more about how much of the drug is needed to protect neurons. He also plans to study how the calcium channels in dopamine neurons interact with the genes linked to PD. If all goes well, he hopes to begin a clinical trial to test the effectiveness of isradipine in people with PD.
Sources:
National Institute of Neurological Disorders and Stroke
"'Rejuvenation' protects neurons in mouse models of Parkinson's disease." Nature, June 28, 2007, Vol. 447, pp: 1081-1086.