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NEUROLOGY 2006;66:S69-S79
© 2006 American Academy of Neurology

Neurology supplements are not peer-reviewed. Information contained in Neurology supplements represent the opinions of the authors and are not endorsed by nor do they reflect the views of the American Academy of Neurology, Editor-in-Chief, or Associate Editors of Neurology.

Rationale for considering that propargylamines might be neuroprotective in Parkinson’s disease

C. Warren Olanow, MD, FRCPC

From the Department of Neurology, Mount Sinai School of Medicine, New York, New York.

Address correspondence and reprint requests to Dr. C. Warren Olanow, Department of Neurology, Mount Sinai School of Medicine, Annenberg 14–94, One Gustave L. Levy Place, Box 1137, New York, NY 10029; e-mail: warren.olanow{at}mssm.edu

A neuroprotective therapy that slows or stops disease progression is the major unmet medical need in Parkinson’s disease (PD). Current evidence indicates that cell death in PD occurs, at least in part, by way of a signal-mediated apoptotic process. This raises the possibility that anti-apoptotic agents might be neuroprotective in PD. Propargylamines have been demonstrated to be potent anti-apoptotic agents in both in vitro and in vivo studies, presumably by maintaining glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a dimer and thereby preventing its nuclear translocation where it blocks upregulation of anti-apoptotic proteins. Selegiline is a monamine oxidase type B (MAO-B) inhibitor that incorporates a propargyl ring within its molecular structure. It was shown to delay the need for symptomatic therapy in untreated PD patients in the DATATOP study, but interpretation is confounded by its symptomatic effects. Rasagiline is another MAO-B inhibitor that contains a propargyl ring and has protective effects in laboratory models. A clinical trial utilizing a delayed start design demonstrated that patients initiated on rasagiline at baseline are improved at one year in comparison to patients initiated on placebo and switched to rasagiline at 6 months even though both groups were on the same treatment for the last 6 months of the study. These results argue against the benefit being due to a symptomatic effect and are consistent with rasagiline having a protective effect.

Publication of this supplement was supported by an educational grant from Teva Neuroscience and Eisai, Inc.

Disclosure: The sponsor has provided the author with personal honoraria (in excess of $10,000) during his professional career.