Treatment of congenital hypomyelinating leukodystrophy using the gene suppression effect of morpholino

2015 Fiscal Year Final Research Report

• Project/Area Number: 25670485
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Inoue Ken 国立研究開発法人国立精神・神経医療研究センター, 神経研究所疾病研究第二部, 室長 (30392418)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: トランスレーショナルリサーチ / 脳神経疾患 / アンチセンス / 発現抑制 / 治療法開発

Outline of Final Research Achievements

Pelizaeus-Merzbacher disease is a hypomyelinating leukodystrophy characterized by failure of myelination. the most frequent mutation is PLP1 duplication that lead to gene overexpression, but no cure is available. In this study, we employed a synthetic antisense oligonucleotide-like reagent, morpholino, to develop a therapy for PLP1 duplication. We designed and produced modified morpholino that can specifically suppress PLP1 expression. We treated PLP1 trasngenic mice by injecting morpholino into ventricle or cerebral parenchyma. However, we found that morpholino is toxic to brain tissue and concluded that morpholino is inappropriate to use in the treatment of PLP1 duplication.

Free Research Field

神経遺伝学、分子生物学、神経科学