Multispecifika antikroppar för förbättrad immunterapi av hjärnsjukdomar
Tidsperiod: 2020-01-01 till 2023-12-31
Projektledare: Greta Hultqvist
Bidragstyp: Bidrag för anställning eller stipendier
Budget: 6 000 000 SEK
Immunotherapy is the most promising strategy for treatment of dementia despite the fact that antibodies pass poorly through the blood brain barrier (BBB). We have previously developed a BBB transporter that increases the antibody uptake in mice almost 100 times. In this project we want to develop the BBB transporter further:Intraneuronal antibody delivery. Tau and a-synuclein aggregates that cause dementia are located in the synapse. To have an effect on these aggregates, the antibody has to pass the BBB but also the cell membrane. We will now develop transporters from peptides that bind to a receptor that is transferred from the outside to the inside of synapse. The transporters will be attached to therapeutic or diagnostic antibodies and we will evaluate if they can enable therapy or diagnostics. We will also search for new targets for intraneuronal transporters and evaluate these. Species-independent BBB transporters. Our current BBB transporter does not work in humans. We will now investigate if surface proteins from viruses infecting both mouse and human brain can be developed into translational BBB transporters. Since such proteins have evolved to take the viruses through the BBB we may be able to use them to transport antibodies into the brain.If successful, the uptake of antibodies in the brain and in synapses will be substantially increased. This will have an enormous potential for improvement of both immunotherapy and diagnostics for all brain diseases.