In a new study from Uppsala University the development of a new antibody design that increases brain uptake of antibodies almost 100-fold is described.
The research group behind this new study has taken advantage of the fact that some large proteins are actively transported across the blood-brain barrier, including transferrin whose primary task is to bind to iron in the blood and then transport it to the brain. The researchers have modified the antibodies they want to transport into the brain using components that bind to the transferrin receptor. Then the receptor transports antibodies into the brain. The number of modifications to and placement of the antibodies have proven to be important factors.
“We’ve placed them so that each antibody only binds with one modification at a time, despite being modified in two places. Our design thus doubles the chances of the antibody binding to the transferrin receptor compared with only one modification. We’ve successfully increased the amount of antibodies in the brain almost 100-fold, which is the largest uptake improvement that has ever been shown,” says Greta Hultqvist, researcher at the Department of Public Health and Caring Sciences at Uppsala University.
The researchers have used the new method on an antibody that binds to a protein involved in the course of Alzheimer’s disease. Without the modification, they could only detect very small quantities of antibody in the brain in a mouse model of Alzheimer’s disease, while they could detect high levels of the modified antibody in the same mice.
“From a long-term perspective, it’s likely that the new format can be used to effectively treat not only Alzheimer’s disease, but also other diseases affecting the brain,” says Dag Sehlin, researcher at the Department of Public Health and Caring Sciences at Uppsala University.
Source: Uppsala University