University of Colorado Denver
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Principal Investigator: Dr. Jeffrey Bennett Project Title: AQP4-Specific Immunotherapy in |
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Neuromyelitis optica (NMO) is a demyelinating disorder that primarily affects the optic nerves and spinal cord. Approximately 70% of affected individuals demonstrate a humoral immune response against the aquaporin-4 (AQP4) water channel. IgG antibodies against the AQP4 protein are found in the serum and cerebrospinal fluid of NMO patients and cause disease-specific pathology when administered to animals with mild central nervous system inflammation. Despite our increased appreciation for the role of AQP4 autoantibodies in NMO disease activity, there is a significant fraction of NMO patients without a detectable humoral immune response to AQP4; and in seropositive patients, 30% of the intrathecal clonally expanded plasma cell response is not directed against AQP4. Therefore a complete understanding of the humoral immune response in NMO and NMO-spectrum disease is lacking. In particular, little is known about the source of CNS AQP4 and non-AQP4 antibodies and their target epitopes. Understanding these issues is critical to developing novel disease therapies and designing strategies for monitoring disease activity. We propose experiments to delineate the target epitopes of NMO autoantibodies, evaluate the relationship between these epitopes and disease pathogenecity, distinguish the source of intrathecal AQP4 autoantibodies, and produce large quantities of NMO-specific monoclonal recombinant antibodies for cell biologic, biophysical, and therapeutic studies. UC Denver NMO Team
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