Antibody drug therapy disrupts amyloid toxicity in the brain

Amyloid plaque is a known neurotoxin and hallmark of Alzheimer’s pathology. There are currently no drugs approved to treat the chronic neurodegenerative disease. Fighting the disease with antibodies is showing encouraging results by negating the neurotoxic damage left in the wake of beta-amyloid aggregation, according to a study published April 30 in the Journal of Neuroscience.

The antibody drug therapy, currently in preclinical phase, interacts with amyloid synaptotoxicity by blocking its effect with protein antibodies called anti-prion protein (PrP) antibodies. Igor Klyubin, a senior research fellow at Trinity College, Dublin, and colleagues assessed its feasibility in action.

“Here, we show that intravascular administration of a high-affinity humanized anti-PrP antibody to rats can prevent the plasticity-disrupting effects induced by exposure to soluble AD [Alzheimer’s disease] brain extract,” wrote the authors. “These results provide an in vivo proof of principle for such a therapeutic strategy.”

Researchers tested whether an intravascular dose of the humanized antibody treatment reached its target and had a significant impact on neurotoxicity by disturbing the normal effect of amyloid plaque in the brain. For this study, the scientists used an anti-PRP antibody called PRN100.

“The potential for anti-PrP antibodies to prevent beta-amyloid synaptotoxicity in AD has been established previously,” added Klyubin et al. “However, no fully humanized anti-PrP antibody potentially applicable to AD patients has been reported.”

Specifically the study looks at disruption of hippocampal long-term potentiation (LTP), a kind of plasticity of the synapses involved in learning and memory.

“We show that PRN100 retains key properties of the parent murine antibody, ICSM18, and can block beta-amyloid induced inhibition of LTP when injected directly into the brain without inducing overt acute neurotoxicity,” the researchers concluded.