Abstract
RHIgM22 is a recombinant human monoclonal IgM designed to promote remyelination, and it is currently in Phase I clinical trials in patients with multiple sclerosis (MS). In animal models of demyelination, a single low dose of rHIgM22 stimulates oligodendrocyte maturation, induces remyelination, preserves axons, and slows the decline of locomotor deficits. Natural autoantibodies like rHIgM22 typically bind to multiple antigens with weak affinity. rHIgM22 binds to oligodendrocytes and myelin. Because the antigens for rHIgM22 is prevalent within and exclusive to central nervous system (CNS) myelin, we used CNS myelin particles in combination with surface plasmon resonance to determine the kinetic and affinity constants for the interaction of rHIgM22 to myelin. We found that both the serum and recombinant forms of the antibody bind to myelin with very small dissociation constants in the 100 pM range, which is highly unusual for natural autoantibodies. The extraordinary affinity between rHIgM22 and myelin may explain why such a low effective dose can stimulate CNS repair in animal models of demyelination and underlie the accumulation of rHIgM22 in the CSF in treated MS patients by targeting myelin.
Original language | English (US) |
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Pages (from-to) | 12567-12573 |
Number of pages | 7 |
Journal | Analytical Chemistry |
Volume | 90 |
Issue number | 21 |
DOIs | |
State | Published - Nov 6 2018 |
Bibliographical note
Funding Information:This work was supported by grants from the NIH (Grant No. R01 GM092993 to A.E.W., M.R., S.-H.O.) and Minnesota Partnership for Biotechnology and Medical Genomics (M.V., L.R.J., N.J.W., L.J.M., A.E.W., M.R., S.-H.O.). N.J.W. and S.-H.O. also acknowledge support from the Institute for Engineering in Medicine at the University of Minnesota. N.J.W. acknowledges support from Lehigh University. S.-H.O. further acknowledges the Sanford P. Bordeau Endowed Chair in Electrical Engineering.
Publisher Copyright:
© 2018 American Chemical Society.