Cottrell DA, Kremenchutzky M, Rice GP, Hader W, Baskerville J, Ebers GC
Brain 1999 Apr;122 (Pt 4):641-7
Univ of Western Ontario, Dept of Clinical Neurological Sciences, London, Canada
PMID# 10219777; UI# 99235183
The natural history of Primary/Progressive Multiple Sclerosis (PP-Multiple Sclerosis) recently has been defined in a geographically based Multiple Sclerosis population.
For a series of prognostically defined hypothetical entry criteria based upon current trends in presentation to the London Multiple Sclerosis Clinic, we determined the number of patients who would have been trial eligible.
Using 23 year mean longitudinal natural history data, we identified the observed rate of deterioration for frequently used trial endpoints.
Hypothetical entry criteria were based on the practical considerations which would attend the execution of clinical trials in Progressive Multiple Sclerosis.
We then developed a series of sample size tables giving the number of patients with PP-Multiple Sclerosis and the length of observation that would be required to detect a significant result.
(P = 0.05) for a 25, 50 and 75% decrease in the median time to progression with 80 or 90% power, with treatment efficacy based upon the ability to slow progression on the Disability Status score.
It is expected that the considerations outlined here will prove useful for both trial design and interpretation of trials in PP-Multiple Sclerosis which will require multi-center collaborative efforts.
Multiple Sclerosis Among Utility Workers
Johansen C, Koch-Henriksen N, Rasmussen S, Olsen JH
Neurology 1999 Apr 12;52(6):1279-82
The Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen
PMID# 10214760; UI# 99229573
The incidence of MS was assessed in a nationwide cohort study of 31,990 employees of Danish utility companies between 1900 and 1993.
Overall, 32 cases of MS were diagnosed, as compared with 23.7 expected from national incidence rates, to yield a standardized incidence ratio of 1.35 (95% confidence interval, 0.92 to 1.91).
We found no support for the hypothesis of an association between occupational exposure to ElectroMagnetic Fields and the risk of MS.
Leber's Hereditary Optic Neuropathy DNA Mutations In Familial Multiple Sclerosis
Mojon DS, Fujihara K, Hirano M, Miller C, Lincoff NS, Jacobs LD, Greenberg SJ
Graefes Arch Clin Exp Ophthalmol 1999 Apr;237(4):348-50
Univ of Bern, Dept of Ophthalmology, Switzerland
PMID# 10208269; UI# 99222950
Leber's Hereditary Optic Neuropathy (LHON) can be difficult to distinguish from Optic Neuritis due to Multiple Sclerosis (MS).
For several decades an association of LHON and MS has been suspected, and within the past 7 years the LHON Nucleotide (nt)-3460 and nt-11778 mtDNA mutations have been identified in several patients with MS-like phenotypes.
To further study this association, we tested 42 index patients with clinically definite, Familial MS for the LHON mtDNA mutations at nt-3460, nt-11778, and nt-14484.
No patients had a Pathogenic LHON mtDNA mutation; however, two MS patients with unilateral Optic Neuritis harbored the nt-15257 mtDNA polymorphism that was reported originally as a Pathogenic LHON mutation.
Several investigators have shown evidence that the nt-15257 mtDNA mutation is not primarily Pathogenic.
Therefore, we conclude that Pathogenic LHON mtDNA mutations are absent or rare in unselected patients with familial, Clinically Definite MS (95% confidence intervals for each of the negative mutations 0-7.0%).
Fridkis-Hareli M, Neveu JM, Robinson RA, Lane WS, Gauthier L, Wucherpfennig KW, Sela M, Strominger JL
J Immunol 1999 Apr 15;162(8):4697-4704
Harvard University, Dept of Molecular and Cellular Biology, and Microchemistry Facility, Cambridge, MA 02138; Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115; and The Weizmann Institute of Science, Dept of Immunology, Rehovot, Israel
Copolymer-1 (Cop-1, poly (Y, E, A, K)) is a random synthetic Amino Acids Copolymer-1 effective in the treatment of Relapsing forms of Multiple Sclerosis (MS).
Cop-1 binds promiscuously, with high affinity and in a Peptide-specific manner to purified MS-associated HLA-DR2 (DRB1*1501) and Rheumatoid Arthritis-associated HLA-DR1 (DRB1*0101) or HLA-DR4 (DRB1*0401) molecules.
In the present work at least 95% of added Cop-1 could be bound to recombinant "empty" HLA-DR1 and -DR4, and 80% could be bound to HLA-DR2 proteins.
Amino Acid composition, HPLC profiles, and sequencing patterns of Cop-1 eluted by acid extraction from HLA-DR molecules were similar to those of the unseparated Cop-1.
Protruding N-terminal ends of Cop-1 bound to HLA-DR1, -DR2, or -DR4 molecules were then treated with Aminopeptidase I, followed by Elution, HPLC, and pool sequencing.
In contrast to untreated or unbound Cop-1, this material exhibited distinct motifs at some positions with increases in levels of E at the first and second cycles, of K at the second and third cycles, and of Y.
Presumably at P1 of the bound Peptide, at the third to fifth cycles, regardless of the HLA-DR molecule employed. No preference was seen at the following cycles that were mainly A.
These first pooled HLA-DR binding Epitopes provide clues to the components of Cop-1 that are biologically active in suppressing MS and possibly Rheumatoid Arthritis.