Parkinson’s / Movement Disorders

Few diseases are more frightening than Parkinson’s. This devastating disorder slowly destroys a part of the brain related to movement and when fully developed, Parkinson’s leaves patients trapped in a body incapable of normal motor function. Parkinson’s disease is a common neurological disorder that impacts approximately 1 million people in the U.S. each year—a number that is rapidly increasing.

WHAT TREATMENTS ARE AVAILABLE?

Until the 1950s, there were no effective treatments for Parkinson’s disease. A major breakthrough came in the late ‘50s and early ‘60s with the discovery that the motor symptoms associated with Parkinson’s disease are a result of selective loss of a specific population of neurons in the brain that use a neurotransmitter called dopamine to control normal movement. These findings led quickly to the discovery that L-DOPA can be converted to dopamine and that administration of L-DOPA can restore dopamine levels in surviving neurons and restore normal motor function in Parkinson’s patients. This breakthrough is an example of new understanding of the basis of a serious brain disorder leading to a subsequent breakthrough in patient care. Early in the course of Parkinson’s disease, L-DOPA and related dopamine replacement therapies are highly effective in treatment of most patients; however, as the disease progresses and dopamine neurons continue to die, Parkinson’s patients slowly stop responding reliably to L-DOPA and develop severe side effects to these medicines. Ultimately, these treatments fail and the disease robs patients of normal motor function. There is a tremendous need for new medicines that can prevent the continued loss of dopamine neurons and/or restore normal movement in a manner that does not depend on the presence of surviving dopamine neurons. Unfortunately, there have been no major advances in developing medicines for treatment of Parkinson’s disease since discovery of L-DOPA in the 1950s. While new medicines have been introduced, all act in a manner that is similar to L-DOPA and provide only incremental advances rather than fundamental improvements in the lives of Parkinson’s patients.

HOW IS THE VANDERBILT CENTER FOR NEUROSCIENCE DRUG DISCOVERY INVOLVED?

Another major breakthrough in the understanding of Parkinson’s disease began to emerge in the 1990s and is now providing new insights into the changes that occur in the brain that lead to the symptoms of Parkinson’s disease after dopamine neurons are lost. It is now understood that specific brain pathways become overactive as dopamine neurons are lost and this hyperactivity leads to the impairments in motor function. This has led to the development of surgical techniques that reduce activity in these pathways and restore motor function to even the most advanced Parkinson’s patients. Those fortunate enough to qualify for and receive this surgery can have their motor function completely restored; unfortunately, this surgery is not available to the vast majority of Parkinson’s patients. This new understanding, however, does provide insights that allow the design of new medicines that can have the same effects on these brain circuits as those currently achieved through surgical techniques. This provides an exciting opportunity to make the largest breakthrough since the discovery of L-DOPA in the 1950s and to take another major step forward in changing the treatment and course of this disorder.