Elaine Aparecida Del Bel Belluz Guimaraes, Ph.D., of University of Sao Paulo will present a lecture entitled: Role of Doxycycline in L-Dopa-Induced Dyskinesia Potential Therapeutic.
Abstract: An often debilitating side effect of therapy for Parkinson's disease is L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. Maintaining benefits of L-DOPA treatment remains an unmet clinical need. Herein we describe the effect of the secondgeneration tetracycline antibiotic in parkinsonian rats presenting L-DOPA-induced dyskinesia. Methods: Animals received unilateral injections of 6 hydroxydopamine into the medial forebrain bundle were then treated with L-DOPA for 14 days, which resulted in the expression of dyskinetic behavior. L-DOPA-primed rats received an acute intraperitoneal injection of doxycycline, minocycline or COL-3 the latter by the intracerebroventricular route. Another group of rats was chronically treated with doxycycline or minocycline concomitantly with the L-DOPA. Results: Acutely administered doxycycline, minocycline or COL-3 ameliorated the L-DOPA induced dyskinesia. The co-treatment of doxycycline or minocycline with the L-DOPA suppressed the development of dyskinesia. The motor esponses to L-DOPA remained intact in the presence of doxycycline (acute and chronic), indicating preservation of L-DOPA benefit. The anti-dyskinetic effect of doxycycline was associated with decreased astrocyte and microglia activation, the production of reactive oxygen species and the expression of cyclooxygenase-2. Metalloproteinase-2/9 activity, metalloproteinase-3 expression and production of reactive oxygen species showed a robust positive correlation with the intensity of L-DOPA-induced-dyskinesia. Conclusion: Tetracycline derivatives could be a promising disease-modifying therapy when administered with L-DOPA. The mechanism of action, although incompletely understood, appears to relate to their antioxidant and anti-inflammatory activities. In view of the long-established use of tetracycline, we propose that these drugs could be an adjunctive therapy to L-DOPA treatment to prevent the generation of dyskinesia.