Immune cells release cytokines that can trigger inflammation and are central to many inflammatory diseases. An MCAM (melanoma cell adhesion molecule) binds to a partner molecule the blood stream then then allows it to infiltrate adjacent tissues, leading to inflammation.
In healthy people, the blood-brain barrier prevents immune cells (lymphocytes) from entering the central nervous system. In people with MS, two types of lymphocytes, CD4 and CD8, find a way to cross the barrier. They then destroy the myelin sheath that protects neurons, resulting in brain lesions.
MCAM may play a crucial role in MS because it is necessary for the migration of both CD4 and CD8 lymphocytes across the blood-brain barrier. Blocking MCAM may delay the onset of MS and significantly slow its progression.
PRX003 binds to MCAM, blocks the route of inflammation, and prevents the migration of CD4 and CD8 lymphocytes into the brain tissue.
In March, Prothena completed a single ascending dose study of PRX003 in healthy participants (NCT02458677). All doses of PRX003 were reported as safe and tolerated following a single infusion up to 30 mg/kg dose. The results showed that PRX003 administration led to more than 95 percent MCAM neutralization.
Adverse effects reported were headache, balance disorder, seasonal allergies, and viral upper respiratory tract infection in 5 percent of participants.
A Phase 1b clinical study of PRX003 in people with psoriasis (NCT02630901) is ongoing.
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