Current and Experimental Therapeutics of Parkinson’s Disease

Three decades after its introduction, levodopa remains the gold standard for the treatment of Parkinson’s disease (PD). Levodopa is the most potent symptomatic antiparkinsonian agent, and it is associated with an increase in quality of life and longevity for patients with PD. Dopamine agonists are increasingly being used, not only as an adjunct to levodopa, but as early therapy aimed at reducing the risk of developing levodopa-induced motor complications. Catechol O-methyltransferase (COMT) inhibitors extend the elimination half-life of levodopa. They are useful as adjunctive treatment for patients with motor fluctuations to increase the time in which patients respond to the drug. There is now increasing interest in using these drugs from the start of levodopa therapy to deliver levodopa to the brain in a more continuous fashion and thereby, it is hoped, further reduce the risk of motor complications. In the advanced stages of the illness, surgical therapies are being performed with increasing frequency based on evidence that they can restore function when medications fail. Ablative, stimulation, and transplant procedures are all currently under investigation. Finally, there are a series of investigational drugs designed to provide neuroprotective effects and/or to block levodopa motor complications that are now being evaluated in the laboratory and in some instances in PD patients. Thus, therapies and investigational approaches to PD have been markedly expanded in the past several years and include treatments and treatment strategies aimed at restoring function to PD patients in the advanced stages of the illness, preventing the development of the motor complications that are the major source of disability for a large percentage of PD patients, and modifying the disease process so as to slow or halt disease progression. Parkinson’s disease is a progressive motor disorder caused