by: Hitesh Katariya and Jagruti Prajapati
James Parkinson described clinical features of the “shaking palsy” disease in 1817, which later became known as Parkinson Disease (PD). It is a progressive central nervous system disorder that results in chronic loss of motor coordination, tremors, and other severe debilitating impairments. The disorder mostly occurs later in life, but it can sometimes be seen in younger adults, as was the case with actor Michael J. Fox who was diagnosed at age 30. However, the disease incidence in adults less than 40 years of age is extremely low.
Isradipine, commonly used as an antihypertensive agent, is a calcium channel blocker (CCB) that helps to slow down the rate at which calcium moves into the heart and blood vessel walls, subsequently lowering blood pressure. Among the various calcium channel blockers used as antihypertensive agents, isradipine is the only one that crosses the blood brain barrier (BBB). The principal motor symptoms of PD are the preferential loss of dopaminergic neurons in the substantia nigra. Recent studies demonstrate that the dopaminergic signals sent by dopaminergic neurons for release of dopamine into the synapses is controlled by sodium and calcium channels with subsequent generation of electrical signals. Simon et al conducted two studies where CCBs were tested for neuroprotection but didn’t show promising results. In a third study, the incidence of PD was reduced upon use of CCBs.
Studies of isradipine for Parkinson disease are moving forward, but the maximum tolerated dose of isradipine remains an issue. The drug and dose originally developed and tested for hypertension interacts with other channels found in the walls of blood vessels leading to side effects that may limit the drug’s clinical utility for PD. Thus, while there is theoretical rationale and the possibility of repurposing isradipine for treatment of PD, much work is still needed to determine the disease modifying capability of isradipine for PD without causing adverse effects. There is still hope for the isradipine to cure PD or reduce disease symptoms.