Authors: Alice Weatherston
Although immunotherapy represents an exciting opportunity for the treatment of Alzheimer’s Disease, success in clinical trials has so far been hindered by the presence of notable inflammatory side effects as a result of the regimens. New research from the University of Southampton (UK) however has revealed a possible solution to the adverse effects of Alzheimer’s immunotherapy treatments, bringing new hope to the field of research.
Thus far, antibodies developed to target amyloid-beta have illustrated success in clearing plaques and reversing cognitive decline in mouse models, however the translation into clinical trials has proven more problematic. Patients have reported considerable side effects, most notably amyloid-related imaging abnormalities, potentially resulting in small bleeds and dangerous swelling of the brain.
In this new study, the research team, led by Jessica Teeling (University of Southampton), set out to alter the interaction between the antibodies and the immune system in order to remove the cause of the side effects.
The team successfully engineered three different murine anti-abeta antibodies (Bapineuzumab (3D6), Crenezumab (mC2) and Gantenerumaband (chGantenerumab) with an IgG2a constant region) then compared their efficacy and neuroinflammatory potential. Utilizing histology and biochemical analysis, they identified that small changes in the anti-amyloid antibodies resulted in the preservation of the immunotherapeutic activity but removed the onset of inflammatory side effects.
Teeling commented: “New antibodies are entering the clinic for Alzheimer’s disease; therefore, it is important to learn all we can from research into these novel interventions and use antibody engineering technology to optimise their effects.”
Jeffrey Stavenhagen (Lundbeck) said: “These studies provide a roadmap of how to apply the advances in antibody engineering to antibody therapeutics that target neurodegenerative diseases. The next generation of antibody drugs to enter the clinic will contain new technologies and enhancements to improve the properties required to clear plaques, while keeping the rest of the brain safe.”
Source: University of Southampton press release; Fuller JP et al. Comparing the efficacy and neuroinflammatory potential of three anti-abeta antibodies. Acta Neuropathol. 130 (5), 699–711 (2015).