Successful experimental gene therapy for Alzheimer’s disease using a novel viral vector system that drives a brain-specific gene expression by intravenous administration

- Having the potential to prevent Alzheimer’s disease by a simple method -
[Points of the research results]
○The development of a viral vector which is capable of expressing a therapeutic gene only in neurons in the brain by administration into circulating blood.

○In this joint research, Nagasaki University contributed the experimental design, analysis of Aβ metabolism of neural cells differentiated from iPS cells, analysis and evaluation of data, and composition and writing of the paper as specialists in Alzheimer’s disease research.

○Clinical application would be possible if technology for large-scale production of the viral vector is developed and the safety for human being are confirmed.

RIKEN (Ryoji Noyori, president) and Nagasaki University (Shigeru Katamine, president) have jointly developed a viral vector which is administered through a circulating blood and expresses a gene only in the brain, and have succeeded in gene therapy to restore Alzheimer’s disease model mice with impaired learning and memory function to the level of wild-type mice. This is the result of a collaborative research group including Takaomi Saido, senior team leader of Lab for Proteolytic Neuroscience at RIKEN Brain Science Institute (Susumu Tonegawa, director), Professor Nobuhisa Iwata and others at the School of Pharmaceutical Sciences of Nagasaki University, Professor Shin-ichi Muramatsu of Jichi Medical University, and Makoto Higuchi, team leader at the National Institute of Radiological Sciences.

In current gene therapy for central nervous system diseases, a viral vector carrying a therapeutic gene has been injected directly into the brain through a pinhole drilled in the skull by surgical procedure. However, this is not easy, and has a drawback that introduction of the gene into a broad range of brain regions is difficult due to a local injection of the viral vector. The joint research group has developed a neuron-specific gene expression vector unnecessary for surgical procedure, that is, this viral vector can bring to gene expression of the gene only in nerve cells in the brain after it was administered to circulating blood vessels. In this study, as one of applications of the viral vector, experimental gene therapy for Alzheimer’s disease was carried out. When the viral vector carrying a gene for neprilysin, an enzyme responsible for degradation of amyloid-β peptides (Aβ) that cause Alzheimer’s disease was administered into Alzheimer’s disease model mice, the amounts of amyloids and Aβ oligomers which have strong neurotoxicity were reduced in the brain, and the impaired learning and memory function was successfully restored to the level of wild-type mice.

The viral vector developed in the present study is an innovative technology that changes the concept of gene therapy for central nervous system diseases, which is thought to have the potential for fundamental prevention or treatment for all Alzheimer’s patients, including those with early onset. Clinical application can be expected when technology to quickly produce the viral vector in a large-scale is developed and safety concerns are resolved.

This research was supported by a MEXT Grant-in-Aid for Scientific Research on Innovative Areas “Foundation of Synapse Neurocircuit Pathology” (Principal investigator: Professor Hitoshi Okazawa of Tokyo Medical and Dental University) and the MEXT commissioned project “Japan Advanced Molecular Imaging Program,” and was reported in the British online journal Scientific Reports (March 18; March 18 in Japan).

*Joint press release

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