New medical and surgical treatments for Parkinson's disease.

This article reviews new medical and surgical treatments for Parkinson's disease (PD). Catechol-O-methyl-transferase (COMT) inhibitors supplement the variety of antiparkinsonian drugs interacting with the dopaminergic system. Clinical studies show that COMT inhibitors prolong the action of levodopa in patients with the "wearing off" phenomenon. The atypical antipsychotic drug clozapine is the treatment of choice for the alleviation of levodopa-induced psychosis. Clozapine also has beneficial effects on tremor and levodopa-induced dyskinesias. Thus, COMT inhibitors and clozapine provide new opportunities for the treatment of patients with longstanding PD and fluctuating responses to levodopa. Experimental evidence in animals suggests that glutamate antagonists have symptomatic and neuroprotective actions in PD. At present, however, only weak antiglutamatergic drugs that have low specificity, such as memantine, amantadine, and budipine are available for clinical studies. Neurotrophic factors, in particular ciliary neurotrophic factor and glial cell line-derived neurotrophic factor, are among the most promising new approaches for neuroprotection in PD. Problems of bioavailability, however, thus far preclude their use in patients. An improved understanding of the pathophysiology of parkinsonism has led to a renaissance of stereotaxic surgery. The subthalamic nucleus is a potential new target for surgical intervention. Ventroposterior pallidotomy has been shown to improve not only rigidity and tremor, but also akinesia. The techniques for thalamic interventions have been refined by introducing chronic thalamic stimulation. Future transplantation approaches to PD will focus on the use of genetically modified cells carrying genes for dopamine-synthesizing enzymes or neurotrophic factors. Animal studies show the feasibility of in vivo gene transfer for the treatment of PD.