Gene therapy for Alzheimer’s disease

Gene therapy for Alzheimer's disease

Yuma Hori, Kaori Watanabe, Masashi Asai, Keiro Shirotani, Nobuhisa Iwata

Department of Genome-based Drug Discovery, Graduate School of Biomedical Sciences, Nagasaki University

In gene therapy for neurological 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 delivery of the gene to a broad range of brain is difficult due to a local injection of the viral vector.  Recently a specific serotype of adeno-associated virus (AAV9) that is capable of crossing the blood-brain barrier and brain-cerebrospinal fluid barrier from circulating blood has been discovered.  By utilizing the virus we have successfully developed a new viral vector system that can provide neuronal gene expression throughout the brains after peripheral administration.
As one of applications of the viral vector, we carried out experimental gene therapy for Alzheimer's disease (AD).  When the viral vector carrying neprilysin gene, an enzyme responsible for degradation of amyloid-β peptides (Aβ) was administered into AD model mice, neprilysin gene expression occurred broadly in the brain and amounts of amyloids and Aβ oligomers 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 is an innovative technology that changes the concept of gene therapy for neurological diseases, and is thought to have the potential for fundamental prevention or treatment for all AD patients, including those with early onset.  Clinical application can be expected when technology to produce the viral vector quickly in a large-scale is developed and safety concerns are resolved.

Address correspondence to Dr. Nobuhisa Iwata, Department of Genome-based Drug Discovery, Graduate School of Biomedical Sciences, Nagasaki University(1-14 Bunkyo-machi, Nagasaki-shi, Nagasaki 852-8521, Japan)