Huntington Beach, CA -
A recent paper from Dr. Agadjanyan's group at the Institute of Molecular Medicine (Movsesyan et al. Reducing AD-like pathology in 3xTg-AD mouse model by DNA epitope vaccine - a novel immunotherapeutic strategy. PLoS ONE 2008 May 7;3(5):e2124) reports the successful treatment of a mouse model of Alzheimer's using DNA vaccination against amyloid protein peptides.
Previously clinical trials were conducted using vaccination towards amyloid protein. Efficacy was associated with antibody responses. Autoreactivity induced by cytotoxic lymphocytes was a cause of potential safety concerns. Although microglial activation is associated with reduction in plaque size in some models (Herber et al. Microglial activation is required for Abeta clearance after intracranial injection of lipopolysaccharide in APP transgenic mice. J Neuroimmune Pharmacol. 2007 Jun;2(2):222-31) , it appears that the main therapeutic effect of amyloid derived peptide vaccination is associated with humoral immunity.
In order to stimulate a specific humoral response, the authors generated a DNA vaccine that contained 3 identical peptides that are B cell epitopes of the amyloid beta protein (1-11), a strong T helper epitope, and a "molecular adjuvant" that acts as a Th2 chemoattractant (CCL22).
Administration of this DNA vaccine to the triple transgenic Alzheimer's mouse model induced a potent Th2 response and high levels of antibodies to Abeta. Importantly, the vaccine prevented behavioural abnormalities, as well as pathological score associated with disease onset. No adverse effects were observed associated with this vaccination.
This important study poses a method of prophylactically using the immune system to prevent a neurodegenerative disorder. Given that recent studies in similar Alzheimer's Disease models have demonstrated a role for endogenous hippocampal stem cells (Ermini et al. Neurogenesis and Alterations of Neural Stem Cells in Mouse Models of Cerebral Amyloidosis. Am J Pathol. 2008 May 8), it will be interesting to see how such immune modulatory approaches may be used together with stem cell therapy.