Authors: Tanya Simuni and D. James Surmeier
Parkinson’s disease (PD) is the second most common neurodegenerative disease that affects 1% of the population above the age 65. The etiology of PD remains unknown. While there are a number of effective symptomatic treatment options for PD, not a single neuroprotective agent has been shown to be effective. The principal motor symptoms of PD are attributable to the preferential loss of dopaminergic neurons in the substantia nigra. Recent data demonstrated that the selective vulnerability of these neurons may be due to the reliance of these neurons on L-type Cav1.3 Ca2+ channels and, more importantly for PD, that blocking these channels with israpadine, a dihydropyridine Ca2+ channel antagonist, protects these neurons in in vitro and in vivo models of parkinsonism. Recent epidemiological data also points to a reduced risk of PD with chronic use of dihydropyridines. This paper reviews the preclinical rationale for the potential neuroprotective effect of isradipine, epidemiological data, and results of the recently completed Phase II study. Our Phase II clinical studies have found that isradipine is safe and tolerable at the daily dose of 10 mg or below in participants with early PD. Phase III efficacy study is being planned.
Keywords: Parkinson’s disease, neuroprotection, clinical trials, isradipine