LAG3 Antibody Alleviates Parkinson’s Disease Pathology by Inhibiting Neuronal and Astrocytic LAG3 via Brain Shuttle–Mediated Delivery

Neuronal lymphocyte-activation gene 3 (LAG3) binds to misfolded α-synuclein (α-syn) and facilitates its endocytosis and cell to cell transmission. The LAG3 and amyloid β precursor-like protein 1 (APLP1) interaction appears to exacerbate Parkinson’s disease pathology. On the other hand, astrocytic LAG3 promotes α-syn propagation through mediating sleep deprivation induced glymphatic dysfunction. LAG3 antibodies, however, provide a possible therapy to Parkinson’s disease dopaminergic cell death and motor deficits by preventing LAG3 from facilitating α-syn pathology. With the blood brain barrier restricting antibody transportation to the brain parenchyma, brain shuttle technology offers a possible solution. A 2x1 format CD98hc brain shuttle LAG3 antibody may allow the delivery of LAG3 antibodies to either neuronal or astrocytic LAG3.