2021 EF Jonathan Cleaver

Jonathan Cleaver

2021 Entry Clinical Fellowship

Leucocyte trafficking and blood-brain barrier dysfunction in neuromyelitis optica spectrum disorder

Neuromyelitis optica spectrum disorder (NMOSD) is a disease which causes inflammation of the nerves supplying the eyes, spinal cord and brain. NMOSD affects 1-10 per 100,000 population and typically causes blindness and paralysis. NMOSD is associated with the presence of proteins called autoantibodies which target the aquaporin-4 (AQP4) protein - found in the central nervous system which includes the brain and spinal cord - and causes inflammation. These antibodies are thought to be created outside of the brain and spinal cord compartment. To cause harmful inflammation they must cross the blood-brain barrier (BBB) - a tight junction of different cells which regulate movement into and out from the brain.

During my fellowship, I have created a model to analyse how the immune system can cross the BBB to enter the central nervous system in NMOSD; allowing us to see which parts of the immune system and/or signals are most effective at facilitating this process. This will facilitate review of novel mechanisms by which the immune system traffics into the brain to cause harmful inflammation and may provide biological evidence to inform new treatment options.