This technology includes a therapeutic approach to prevent secondary edema after cerebrovascular hemorrhage. Using an animal model, we found that edema is triggered by massive extravasation of myelomonocytic cells from the blood into the brain in response to hemorrhaging vessels. Administration of anti-LFA1 and anti-VLA4 antibodies resulted in an inhibition of extravasation of the myelomonocytic cells. This single dose treatment prevented secondary edema and markedly improved functional outcomes if administered within the first six hours following cerebrovascular hemorrhage. Moreover, these two antibodies had to be administered in combination, as neither antibody alone was effective.
This technology can be developed into a combination anti-LFA1/VLA4 therapy that can be administered intravenously in emergency situations when acute brain swelling develops in response to brain injury, intracranial hemorrhage, stroke, cerebral malaria, etc. Simultaneous intravenous injection of anti-LFA1/VLA4 can rapidly reduce brain swelling by displacing immune cells from CNS vasculature. This therapy is also far more effective than administering anti-LFA1 and anti-VLA4 alone and should have a better safety profile because it will only be given once.
This single dose anti-adhesion molecule therapy will have broad-reaching clinical relevance, offering the ability to quickly treat several life-threatening CNS disorders associated with immune-mediated brain swelling.