Research Summary:
Alzheimer's and Parkinson's disease are associated with inappropriate clustering of proteins called beta-amyloid and alpha-synuclein, respectively, which can lead to toxic brain deposits. BrightFocus-funded researcher and senior author Dr. Peter Tessier led a team that developed specialized antibodies to target and neutralize specific "sticky" sites on the protein where the clustering takes place. Based on their study of the 3D-structures and protein sequences of the sticky sites, the team designed antibodies that have about ten times the ability of a regular antibody to neutralize the toxic clustering of the misfolded Alzheimer's beta-amyloid protein (and alpha-synuclein for Parkinson's).

Significance:
Typically, only a small percentage of therapeutic antibodies delivered by injection into the blood can make it to target regions in the brain. Therefore, the antibodies that do make it past the blood-brain barrier would need to compensate for their low levels with a higher amount of activity. This need has now been addressed through the team's novel method of creating high-binding-activity antibodies—the number of proteins neutralized was improved from 1-2 proteins by each conventional antibody to 10 proteins by the new specialized antibodies. More testing needs to be done, but this new antibody design method could be applied to developing future therapies for neurodegenerative diseases like Alzheimer's and Parkinson's.

• BrightFocus-funded research grant to Peter Tessier, Ph.D.
• Original Scientific Publication
• Original Press Release