Técnicas de Edición de Acidos Nucléicos en Parkinson´s Disease

Repression of SNCA expression by reducing its mRNA level through the use of nucleic acid medicine may lead to suppression of α-synuclein protein levels and prevention of neurodegeneration (1).

Type of editing and Target Organ	New techniques of drug delivery have been attempted to downregulate α-synuclein expression in the brain have been done using ex vivo experiments in rat models.
Administration and Technique	The technique per se, consists in systemic injection of modified exosomes expressing Rabies virus glycoprotein loaded with siRNA targeting SNCA into the mouse tail vein resulted in widespread distribution of siRNA in the brain and around 50% reduction of SNCA mRNA and protein expression in the midbrain and striatum.
Directed To	These approaches are delivered to experimental models that, if successfully work, will be applied to human brains.
Directed By	These experiments are supported by the Michael J. Fox Foundation for Parkinson’s Research, the American Parkinson Disease Association, and the New Jersey Health Foundation/Nicholson Foundation, and by grants from the US National Institutes of Health.
Short-Mid-Long Term Results	However, none of these approaches has produced ideal outcomes, and achieving long-term effects has proven challenging due to intracellular instability of these RNA-based nucleic acid compounds. Additionally, AAV-mediated expression of shRNA-SNCA can have negative effects such as increased inflammatory response, reduced TH expression, and nigrostriatal degeneration.

Reference:
1. Nakamori M, Junn E, Mochizuki H, Mouradian M. Nucleic Acid–Based Therapeutics for Parkinson’s Disease. Neurotherapeutics. 2019;16(2):287-298.

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