Copolymer 1 as therapy for multiple sclerosis: the cons.
One of the hallmarks of multiple sclerosis (MS) is intra-blood-brain-barrier (BBB) IgG synthesis, a byproduct of plasma cells located in and around active inflammatory demyelinating plaques. The rate of IgG synthesis can be measured by plugging CSF and blood IgG and albumin concentrations into our equation. When done in conjunction with CSF and serum analyses for IgG oligoclonal bands, 99% of definite MS patients demonstrate intra-BBB IgG synthesis. At autopsy the pathologic criterion of an inactive plaque of demyelination is absence of inflammatory cells. Hence, we propose that modulation downward or eradication of intra-BBB IgG synthesis (ie, a manifestation of reduced white matter inflammation) in a living patient is a reasonable therapeutic criterion and goal of MS therapy. In a preliminary trial of five severely disabled MS patients, we evaluated the effects of copolymer 1 (COP-1) in daily intramuscular doses of 20 mg (2 patients) and twice daily subcutaneous doses of 15 mg (3 patients) on clinical parameters and on intra-BBB IgG synthesis over a 2-month study period. The results of this trial showed no beneficial effect on neurologic function or on inflammatory demyelination, as assessed by monitoring of intra-BBB IgG synthesis.
Baumhefner
R W
RW
Neurology Service, VA Wadsworth Medical Center, Los Angeles, CA 90073.
Tourtellotte
W W
WW
Syndulko
K
K
Shapshak
P
P
Osborne
M
M
Rubinshtein
G
G
D000328:Adult; D000917:Antibody Formation; D004341:Drug Evaluation; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000628:therapy*; D010455:Peptides / Q000627:therapeutic use / Q000633:toxicity*
D007074:Immunoglobulin G; D010455:Peptides; C021759:(T,G)-A-L