Journal of Gene Therapy Aspects

Journal of Gene Therapy Aspects

ISSN 2057-164X
Original Research

Gene therapy using synthetic microRNA directed against GAD67 has beneficial effect on motor behaviour in 6-OHDA lesioned rats

Erika Elgstrand Wettergren, Luis Quintino and Cecilia Lundberg*

*Correspondence: Cecilia Lundberg

Author Affiliations

Department of Experimental Medical Science, CNS Gene Therapy Unit, BMC A11, Lund University, Lund, Sweden.


Background: Modification of the glutamic acid decarboxylase (GAD) level is a promising future treatment tool for Parkinson's disease (PD). GAD is the rate-limiting enzyme in the synthesis of the inhibitory neurotransmitter gamma amino butyric acid (GABA) and modification of the GAD level could therefore potentially be used to alter the GABA output from a nucleus.

Methods: We have previously developed a synthetic microRNA (smiRNA1550) designed to knockdown the GAD isoform GAD67 and shown that it can efficiently knockdown the target protein. In this study we have further evaluated the therapeutic potential of smiRNA1550 in treating motor symptoms using the 6-OHDA rat model of PD and lentiviral vectors. The smiRNA was evaluated in striatum and substantia nigra pars reticulata (SNpr), two nuclei with increased GAD levels and GABA output in PD. The result was evaluated by behaviour tests and western blot. Differences between groups were assessed using analysis of variance (ANOVA) followed by the Tukey's multiple comparison test for group comparisons.

Results: There was a beneficial effect in apomorphine-induced rotations after injection of LV-smiRNA1550 into SNpr.

Conclusion: These findings suggest that manipulation of the GABA system could be a valid approach for development of novel gene therapies for PD that warrant further study.

Keywords: Glutamic acid decarboxylase, synthetic microRNA, striatum, substantia nigra pars reticulata, parkinson's disease, rat

ISSN 2057-164X
Volume 1
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