Nonviral Abeta DNA vaccine therapy against Alzheimer's disease: long-term effects and safety.
It was recently demonstrated that amyloid beta (Abeta) peptide vaccination was effective in reducing the Abeta burden in Alzheimer model mice. However, the clinical trial was halted because of the development of meningoencephalitis in some patients. To overcome this problem, anti-Abeta antibody therapy and other types of vaccination are now in trial. In this study, we have developed safe and effective nonviral Abeta DNA vaccines against Alzheimer's disease. We administered these vaccines to model (APP23) mice and evaluated Abeta burden reduction. Prophylactic treatments started before Abeta deposition reduced Abeta burden to 15.5% and 38.5% of that found in untreated mice at 7 and 18 months of age, respectively. Therapeutic treatment started after Abeta deposition reduced Abeta burden to approximately 50% at the age of 18 months. Importantly, this therapy induced neither neuroinflammation nor T cell responses to Abeta peptide in both APP23 and wild-type B6 mice, even after long-term vaccination. Although it is reported that other anti-Abeta therapies have pharmacological and/or technical difficulties, nonviral DNA vaccines are highly secure and easily controllable and are promising for the treatment of Alzheimer's disease.
Okura
Yoshio
Y
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Musashidai 2-6, Fuchu, Tokyo 183-8526, Japan.
Miyakoshi
Akira
A
Kohyama
Kuniko
K
Park
Il-Kwon
IK
Staufenbiel
Matthias
M
Matsumoto
Yoh
Y
D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000097:blood; D049109:Cell Proliferation; D004279:DNA, Viral / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D051379:Mice; D013997:Time Factors; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*
D016229:Amyloid beta-Peptides; D000906:Antibodies; D004279:DNA, Viral; D019444:Vaccines, DNA