A NONINVASIVE TRANSPORT-SYSTEM FOR GDNF ACROSS THE BLOOD-BRAIN-BARRIER

GLIAL cell line-derived neurotrophic factor (GDNF) is a neurotrophin w hich supports midbrain dopaminergic neurons and spinal cord motorneuro ns. GDNF has been proposed as a possible therapeutic agent for Parkins on's disease, spinal cord injury or motorneuron degenerative disorders . Administration of GDNF is complicated by its poor penetration across the blood-brain barrier (BBB). Central nervous system capillaries are uniquely enriched in transferrin receptors and antibodies to these re ceptors (OX-26) have been proposed as potential carriers to transport large molecules across the BBB. Intravenous administration of an OX-26 -GDNF conjugate enhanced survival of spinal cord motorneurons in intra ocular transplants, which possess an organotypic BBB. This suggests th at the OX-26-GDNF conjugate could be utilized for non-invasive treatme nt of neurodegenerative diseases of the spinal cord or midbrain dopami nergic neurons.