Calcium Channel Antagonists as Disease-Modifying Therapy for Parkinson's Disease: Therapeutic Rationale and Current Status

I saw James Surmeier (http://physio.northwestern.edu/research/research-areas/systems-neuroscience.html#surmeier) talking on this subject at the Parkinson's UK Research Conference in Leeds earlier this week... he was very inspiring. I was already aware of the epidemiological research on this topic, but not the animal studies that support it... exciting times for calcium channel blockers and PD...

CNS Drugs. 2016 Nov 8. [Epub ahead of print]
Swart T, Hurley MJ.

http://link.springer.com/article/10.1007%2Fs40263-016-0393-9

Parkinson's disease is a disabling hypokinetic neurological movement disorder in which the aetiology is unknown in the majority of cases. Current pharmacological treatments, though effective at restoring movement, are only symptomatic and do nothing to slow disease progression. Electrophysiological, epidemiological and neuropathological studies have implicated CaV1.3 subtype calcium channels in the pathogenesis of the disorder, and drugs with some selectivity for this ion channel (brain-penetrant dihydropyridine calcium channel blockers) are neuroprotective in animal models of the disease. Dihydropyridines have been safely used for decades to treat hypertension and other cardiovascular disorders. A phase II clinical trial found that isradipine was safely tolerated by patients with Parkinson's disease, and a phase III trial is currently underway to determine whether treatment with isradipine is neuroprotective and therefore able to slow the progression of Parkinson's disease. This manuscript reviews the current information about the use of dihydropyridines as therapy for Parkinson's disease and discusses the possible mechanism of action of these drugs, highlighting CaV1.3 calcium channels as a potential therapeutic target for neuroprotection in Parkinson's disease.