The Future of Isradipine and Parkinson's Disease

Can Isradipine reverse neuronal degeneration in Parkinson's?
Parkinson's is a common neurological disease, affecting over 1.5 million people in the USA alone. The risk of PD increases as we get older, especially after we pass sixty. PD progression is the result of the damage and on-going deterioration of the dopamine neurons.

Because dopamine is a chemical messenger for the brain, the death of its neurons causes an ever increasing slow loss of motor control as it causes the typical PD symptoms: tremor, balance, loss of sense of smell, stiffness, inability to dress one's self, swallowing and speaking problems, sleeping issues, sexual dysfunction, dystonia, depression, apathy and many others.

There is a great deal of research underway but there is no cure. The only drug that has some proven neuro-protection thus far is Azilect.

Researchers understand that the neurons die but not much about how or why. While there are signs of the disease process in many regions of the brain, the core symptoms of PD occur when the dopamine neurons in an area of the brain called the substantia nigra pars compacta are damaged. Although in their youthful stage they relied upon sodium channels, as these neurons age they rely on calcuim channels to maintain autonomous activity. This reliance puts the metabolic mitocondria under sustained stress causing cell aging and death.

The calcium channels underlying the autonomous activity of the dopamine neurons are similar to the L-type channels of the heart and smooth muscles. Systemic administration of Isradipine, an L-type blocker of C type channels (Ca2+) causes a reversion to a sodium mechanism to produce independent activity.

Reversion to the sodium and HCN channels found in the juvenile substantia nigra offers protection from toxins to lab rodents with experimental PD. In a few years this could result in a Parkinson's Disease neuroprotective usage for a drug class that has been safely used by cardiac patients for decades. There is the possibility that reversing the synaptic dysfunction, neuron degeneration and reduced plasticity can restore brain cellular and molecular homeostasis; a return to normalcy.

Now there is a fresh approach to combating this disease, a different viewpoint. Isradipine Phase II clinical trials for safety and efficacy begin May 2009.

This research also suggests that although genetic and environmental factors can hasten its onset, PD is programed into all humans, if we live long enough we may all get it.

Resources:

10/06/2007
Calcium, aging and neuronal vulnerabilty in Parkinson's Disease
PUB MED NIH
D. J. Surmeier

07/05/07
Parkinson's disease: return of an old prime suspect
PUB MED NIH
D Sulzer, Y Schmitz

06/06/07
Calcium and Neurodegeneration
PUB MED NIH
MP Mattson

06/28/07
"Rejuvenation" protects neurons in mouse models of Parkinson's disease
PUB MED NIH
CS Chan, JN Guzman, E Ilijic, JN Mercer, C Rick, R Tkatch, GE Meredith, DJ Surmeier