These properties are very promising devices for gene therapy of n

These properties are very promising devices for gene therapy of new age (Cytoplasmic Gene Therapy) because of its genotoxicity-free nature. Further, it is non-pathogenic for humans. Since Sendai virus is a murine parainfluenza virus (PIV) with certain homologies to human PIV, it was tested

as xenotropic vaccine in African Green monkeys and humans without any significant adverse reactions [34] and [35]. Recombinant SeV vector carrying human PIV was also tested in rats [36] and [37]. Further, recombinant SeV vaccine for human immunodeficiency virus (HIV) infection is going to be tested in humans (http://www.dnavec.co.jp/en/index.html). Thus, safety of Sendai virus vector is gradually established. We inserted mouse IL-10 cDNA to construct rSeV-Aβ with the aim of helping antibodies productions and suppressing Th1 type T cell activations. Nasal administration of rSeV-Aβ without IL-10 had less effect to remove see more Aβ depositions (data not shown). Recently, soluble Aβ oligomers, but not fibrils nor learn more monomers, have been considered responsible for cognitive dysfunction prior to the formation of Aβ plaques [22], and Aβ*56, a 56-kDa soluble Aβ dodecamer was found responsible in Tg2576 mice [29]. Our nasal vaccine efficiently reduced not only senile plaque amyloid but also the contents of Aβ*56 oligomer without changing sAPPα and improved cognitive dysfunction in water

maze, Y-maze and contextual fear test which could evaluate hippocampus-related cognition. Thus, our vaccine, if applicable, can be given at the stage of mild cognitive impairment or earlier. Aβ is released from presynaptic sites and deposited in these extracellular plaques [38], and APP and synaptophysin are co-localized at the growth cones of developing neurons in culture [39]. These reports have indicated that Aβ deposition plays an important role in degeneration of presynaptic structures. In addition, it is reported that Aβ oligomers

directly disrupt synaptic structures [40]. In our study, synaptophysin staining showed amelioration of presynaptic degeneration following our nasal vaccine at 24 months old, suggesting prevention of synaptic degeneration or repair of synaptic structures after removal of Aβ deposits including Aβ oligomers. Our next plan is to see whether Tg2576 mice show improvement of cognitive functions by eliminating senile plaque amyloid even at 24 months old. In conclusion, a new vaccine using Sendai virus vector with Aβ and IL-10 cDNA was developed. A nasal administration of this vaccine reduced amyloid burden including Aβ oligomers significantly in AD mice and improved cognitive functions without causing side effects such as brain inflammation. This vaccine can be used to treat and prevent Alzheimer disease. Authors are grateful to Dr. Y. Noda at Meijo University, Dr. T. Nagai at Nagoya University, and Dr. M.

Leave a Reply

Your email address will not be published. Required fields are marked *

*

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>