myelin-basic-protein and roquinimex

A significant correlation exists between disability and the volume of black holes (BHL VOL), defined as hypointense lesions on T1-weighted cranial magnetic resonance imaging. A consistent correlation has also been reported between urinary myelin basic protein-like material (MBPLM) and the transition toward secondary progression (SP) from relapsing-remitting (RR) multiple sclerosis (MS).. To improve the management of MS through a noninvasive and cost-effective test for monitoring disease activity or disease status.. From 662 patients with MS (86 with RR MS, 259 with SP MS without continued attacks, and 317 with SP MS with continued attacks), 24-hour urine samples were obtained at enrollment in the phase 3 Linomide (roquinimex) drug study. The urine specimens were analyzed for MBPLM and correlated with clinical features and findings on cranial magnetic resonance imaging.. Significant but weak correlations existed between urinary MBPLM and BHL VOL in all patients with MS (r = 0.114, P =.003; n = 662), patients with SP MS without attacks (r = 0.185, P =.003; n = 259), and all patients with SP MS (r = 0.122, P =.003; n = 576). No significant correlations were detected in the RR MS group or any of the disease groups or subgroups whose Expanded Disability Status Scale score was 5.0 or lower. In subgroup analysis, the most significant correlation was detected between urinary MBPLM after adjustment for creatinine and BHL VOL in patients with SP MS with an Expanded Disability Status Scale score of 5.5 or higher but without continued relapses (r = 0.417, P<.001; n = 138).. In patients with advanced SP MS, urinary MBPLM may possibly serve as an indicator of failed remission and axonal damage. Urinary MBPLM correlates with disease status in MS, especially the transition of RR MS to SP MS with advancing disability.

Topics: Adjuvants, Immunologic; Axons; Brain; Cost-Benefit Analysis; Cross-Sectional Studies; Disability Evaluation; Disease Progression; Female; Humans; Hydroxyquinolines; Magnetic Resonance Imaging; Male; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Myelin Basic Protein; Predictive Value of Tests; Randomized Controlled Trials as Topic; Severity of Illness Index

Linomide (quinoline-3-carboxamide), a well tolerated, orally administered compound was recently shown to be effective in the prevention and treatment of several autoimmune diseases in experimental animal models. We have investigated its effect on specific humoral immune responses directed to T-cell-dependent soluble or particulate antigens and to a T cell-independent antigen in several mouse strains. Linomide administered after antigen priming did not affect primary and secondary antibody responses directed to T-cell particulate antigens (SRBC) or soluble antigens given with or without complete Freund's Adjuvant (CFA). Linomide treatment given prior to antigen priming did not affect the antibody response to a soluble antigen (TNP-KLH) given with an adjuvant. In contrast, dose-dependent down regulation of primary antibody responses was observed when T cell-dependent (BSA-dextran) or T-cell-independent (TNP-Ficoll) antigens were administered in an immunogenic form without adjuvant after starting Linomide treatment. The primary anti-SRBC antibody response was also suppressed by high dose Linomide given prior to immunization although normal secondary responses were retained. It is worth noting that no immunosuppressive effects on antibody responses were found at low dose ranges which effectively reversed T cell dependent autoimmune manifestation.

Topics: Animals; Antibody Formation; Antigen Presentation; Antigens, T-Independent; Autoantibodies; Autoantigens; Autoimmune Diseases; Dextrans; Diabetes Mellitus, Type 1; Drug Administration Schedule; Encephalomyelitis, Autoimmune, Experimental; Female; Ficoll; Freund's Adjuvant; Haptens; Hemocyanins; Hydroxyquinolines; Immunization; Immunologic Factors; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Mice, Inbred NOD; Myelin Basic Protein; Peptide Fragments; Serum Albumin, Bovine; Solubility; Trinitrobenzenes