Neuroprotective therapy in Parkinson's disease and motor complications: a search for a pathogenesis-targeted, disease-modifying strategy.
The introduction of levodopa in the late 1960s represented a landmark in the therapy of Parkinson's disease (PD). However, motor complications of chronic levodopa therapy have emerged as a major limitation of this otherwise effective therapy. Advancing medical and surgical treatment of these complications has been the main objective of clinical trials during the past few decades. In addition, basic research has focused on better understanding of the mechanisms of motor complications and how to prevent them. Slowing or delaying the progression of the disease delays the need for levodopa therapy; therefore, neuroprotective strategies may play an important role in preventing the onset and reducing the severity of levodopa-related adverse effects. In this introductory review, we present the rationale for current and experimental therapies designed to favorably modify the progression of PD. If implemented early in the course of the disease, such treatments, if found effective, may not only alter the natural progression of the disease but may also delay or minimize motor and nonmotor complications associated with levodopa.
Olanow
C Warren
CW
Department of Neurology, Mount Sinai School of Medicine, Annenberg 14-94, One Gustave L. Levy Place, New York, NY 10029, USA. warren.olanow@mssm.edu
Jankovic
Joseph
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003067:Coenzymes; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000209:etiology* / Q000517:prevention & control*; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D008565:Membrane Proteins; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000627:therapeutic use; D014810:Vitamin E / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000978:Antiparkinson Agents; D003067:Coenzymes; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007189:Indans; D008565:Membrane Proteins; D018696:Neuroprotective Agents; C031967:rasagiline; D014451:Ubiquinone; D014810:Vitamin E; D007980:Levodopa; D016202:N-Methylaspartate; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C024989:coenzyme Q10