A human antibody that promotes remyelination enters the CNS and decreases lesion load as detected by T2-weighted spinal cord MRI in a virus-induced murine model of MS.
The human monoclonal antibody rHIgM22 enhances remyelination following spinal cord demyelination in a virus-induced murine model of multiple sclerosis. Using three-dimensional T2-weighted in vivo spinal cord magnetic resonance imaging (MRI), we have therefore assessed the extent of spinal cord demyelination, before and after 5 weeks of treatment with rHIgM22, to determine whether antibody enhanced remyelination can be detected by MRI. A significant decrease was seen in T2 high signal lesion volume following antibody treatment. Histologic examination of the spinal cord tissue reveals that this decrease in lesion volume correlates with antibody promoted remyelination. To show that rHIgM22 enters the spinal cord and colocalizes with demyelinating lesions, we used ultrasmall superparamagnetic iron oxide particle (USPIO)-labeled antibodies. This may be considered as additional evidence to the hypothesis that rHIgM22 promotes remyelination by local effects in the lesions, likely by binding to CNS cells. The reduction in high signal T2-weighted lesion volume may be an important outcome measure in future clinical trials in humans.
Pirko
Istvan
I
Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Ciric
Bogoljub
B
Gamez
Jeff
J
Bieber
Allan J
AJ
Warrington
Arthur E
AE
Johnson
Aaron J
AJ
Hanson
Dennis P
DP
Pease
Larry R
LR
Macura
Slobodan I
SI
Rodriguez
Moses
M
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology* / Q000821:virology; D009186:Myelin Sheath / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors
D000906:Antibodies