Disease-modifying strategies and challenges in PD

L-Dihydroxyphenylalanine (levodopa, or l-dopa) has long been the gold standard of treatment for Parkinson’s disease (PD), providing both effective treatment for symptoms and a reduction in mortality rate.1,2⇓ However, its high incidence of treatment-related complications has prompted a shift to the use of dopamine agonists (DAs) as first-line monotherapy in the early stages of this disorder and as adjuvant treatment in the later stages.3-5⇓⇓

DAs may have the potential to alter the natural course of PD and levodopa-induced complications through possible neuroprotective actions, which may include (a) a levodopa-sparing effect, (b) stimulation of dopamine autoreceptors, (c) direct antioxidant effects, (d) a reduction in excitotoxicity, and (e) restoration of dopaminergic tone to the dopamine-denervated brain.6,7⇓ The potential benefits of DAs were underscored by the results of the 2-year extension of the Comparison of the Agonist Pramipexole vs Levodopa on Motor complications in Parkinson’s disease (CALM-PD) study,8 which demonstrated a reduction in loss of striatal [¹²³I]-β-CIT uptake, a marker of dopamine neuron density, with the initiation of pramipexole as opposed to levodopa.

On May 9, 2002, clinicians in the field of PD convened at a summit held in Prague, Czech Republic. Their purpose was to present reports of the latest findings concerning PD, to assess disease-modifying drugs, and to discuss the most current strategies in the management of motor complications.

A series of breakout sessions, with discussion groups moderated by faculty members, was included as part of the overall agenda of the symposium. These subgroups were designed to explore the opinions held and treatment strategies employed by clinicians in the forefront of their specialized field and to elicit their comments. Summaries of these discussions are reported below.