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.