Intramuscular delivery of a single chain antibody gene prevents brain Aβ deposition and cognitive impairment in a mouse model of Alzheimer's disease

Anti-beta-amyloid (A beta) immunotherapy is effective in removing brain AD. but has shown to be associated with detrimental effects We have demonstrated that Adeno-associated virus (AAV)-mediated delivery of an anti-A beta single chain antibody (scFv) gene was effective in clearing brain A beta without eliciting any inflammatory side effects in old APP(Swe)/PS1dE9 transgenic mice. In the present study, we tested the efficacy and safety of intramuscular delivery of the say gene in preventing brain A beta deposition The scFv gene was intramuscularly delivered to APP(Swe)/PS1dE9 transgenic mice at 3 months of age, prior to A beta deposition in the brain Six months later, we found that the transgenes were expressed in a stable form at the delivered sites, with a small amount of ectopic expression in the liver and olfactory bulb Blain A beta plaque formation, A beta accumulation, AD-type pathologies and cognitive impairment were significantly attenuated in scFv-treated APP(Swe)/PS1dE9 transgenic mice relative to EGFP-treated mice Intramuscular delivery of scFv gene was well tolerated by the animals, did not cause inflammation or microhemorrhage at the gene expression site and in the brain, and did not induce neutralizing antibodies in the animals These findings suggest that peripheral application of scFv is effective and safe in preventing the development of Alzheimer's disease (AD), and would be a promising non-inflammatory immunological modality for prevention and treatment of AD (C) 2010 Elsevier Inc All rights reserved