RNAi Gene Therapy for Parkinson's Disease

Researchers have developed a tool for preventing synthesis of the protein alpha-synuclein, which accumulates to toxic levels in neurons or glia in Parkinson's disease and other related neurodegenerative syndromes.

Investigators at Northwestern University (Evanston, IL, USA) identified a 21-nucleotide sequence in the coding region of the human á-synuclein gene that proved an effective target for robust silencing by the interference RNA (RNAi) technique. This was demonstrated through the allele-specific silencing of the A53T mutant of human alpha-synuclein.

A method for delivering the interfering RNA into the target nerve cells was created by using a dual cassette lentivirus that co-expressed the alpha-synuclein-targeting small hairpin RNA (shRNA) and an enhanced green fluorescent protein (EGFP) as a marker gene. Results published in the February 7, 2006, online edition of Experimental Neurology showed that the RNA delivered by the virus was effective in silencing endogenous human alpha-synuclein in vitro in the human dopaminergic cell line SH-SY5Y and also of experimentally expressed human alpha-synuclein in vivo in rat brain.

"This is the first step in developing a new therapy for Parkinson's disease based on molecular knowledge of the disease,” said first author Dr. Mohan K. Sapru, assistant professor of pediatrics at Northwestern University.




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