Immunotherapy for neurodegenerative disease in the intracellular domain

Many of the most powerful drugs of recent years rely on antibodies, molecules that are produced by the immune system and bind specifically to certain proteins. Whilst more than 100 antibodies have entered the clinic, all of these bind to proteins outside of our cells. We have shown that if antibodies can get inside cells, a receptor called TRIM21 will recognise the antibody and degrade the antibody and its target. This suggests that if there is a way to get antibodies inside cells, then we may be able to devise new forms of therapy in a wide range of conditions, in particular neurodegenerative diseases. We found that this strategy can indeed be used to target tau, a protein which aggregates inside cells in Alzheimer's disease and other dementias. This work will define how antibodies can get inside cells in order to devise new strategies for future therapies.