Passive immunotherapy - a viable treatment for Alzheimer's disease

Passive immunotherapy is one of the most exciting and extensively researched areas in the field of Alzheimer's disease (AD) today, harbouring the potential to become the first disease-modifying treatment for the disease. The interest in immunotherapy as a treatment stemmed from the significant dangers of toxic side-effects and major obstacles in selectivity for currently pursued therapies against amyloid beta (Aβ) proteins and neurofibrillary tangles. Passive immunotherapy especially, has received much limelight, seen as having the potential to be the safer alternative to active immunisation which encountered a significant setback with the notorious AN-1972 trial in which 6% of the vaccinated patients developed meningoencephalitis. At present, passive immunisation research in animal models have exclusively focused on targeting Aβ proteins, a widely accepted pathology of AD. Following on from this, the preliminary results of phase II trials of three distinct passive immunisation strategies were demonstrated at the 2008 International Conference on Alzheimer's Disease (ICAD). The three therapeutic strategies each targeted the N-terminal of Aβ, the central epitope or utilised a polyclonal approach. The results demonstrated potential as well as caution. Efficacy was undoubtedly present but not to the extent that was hoped and side-effects, most notably vasogenic oedema occurred in the N-terminal targeting antibody, bapineuzimab. Lessons have been learnt by identifying the possible cause of the problems and have been taken on board to nurture the proven efficacious results. Key points to be addressed currently are dosage of the agent to ensure that high enough concentrations enter the central nervous system to be available to cause effect and early enough time of administration to cause effect. The results of the efficacy and safety phase III trials and the development of newer passive immunotherapeutic agents addressing the problems are eagerly awaited in the hope of finally yielding a disease modifying therapy of AD.