Immunomodulation with linomide: possible novel therapy for multiple sclerosis

1996 ◽  
Vol 2 (4) ◽  
pp. 206-210 ◽  
Author(s):  
O Abramsky ◽  
D Lehmann ◽  
D Karussis
Keyword(s):  
Multiple Sclerosis ◽  
Inhibitory Effect ◽  
Progressive Multiple Sclerosis ◽  
Autoimmune Response ◽  
Novel Therapy ◽  
Double Blind ◽  
Mri Scans ◽  
Chronic Relapsing Eae ◽  
The Mean ◽  
T Cell Lines

Linomide, a synthetic quinoline carboxamide, has the ability to stimulate various lymphocyte subpopulations. We have shown its inhibitory effect on the clinical and histological signs of acute and chronic relapsing EAE. In these models linomide induces suppression of lymphocyte response to antigens, production of autoantibody, antigen presentation to specific T-cell lines and Mac-1 expression, and induces activation of NK and suppressor-inducer cells. We have subsequently shown its inhibitory effect on clinical and MRI signs of patients with secondary progressive multiple sclerosis. Results of a double blind, placebo controlled, short term pilot study with p.o. linomide, showed a significant effect on the clinical disability scale (EDSS) (P=0.045) and on the mean total number of new lesions in serial monthly MRI scans (P=0.021). The increase of CD45Ra, CD8 and CD16 positive cells in linomide treated patients may indicate the importance of suppressor-inducer, suppressor and NK cells for the inhibition of the autoimmune response in the disease.

scholarly journals Over three decades study populations in progressive multiple sclerosis have become older and more disabled, but have lower on-trial progression rates: A systematic review and meta-analysis of 43 randomised placebo-controlled trials

2018 ◽  
Vol 25 (11) ◽  
pp. 1462-1471 ◽  
Author(s):  
Richard S Nicholas ◽  
Erika Han ◽  
Joel Raffel ◽  
Jeremy Chataway ◽  
Tim Friede
Keyword(s):  
Multiple Sclerosis ◽  
Meta Analysis ◽  
Progressive Multiple Sclerosis ◽  
Controlled Trials ◽  
Primary Progressive Multiple Sclerosis ◽  
Double Blind ◽  
Trial Entry ◽  
Disability Status ◽  
The Mean ◽  
Meta Analyses

Background: Progression is the major driver of disability and cost in multiple sclerosis (MS). However, the search for treatments in progressive multiple sclerosis (PMS) has not mirrored the success in relapsing MS. Objectives: To assess changes in PMS trials over time. Methods: PubMed, MEDLINE and Embase were searched to identify randomised, double-blind, placebo-controlled trials in PMS. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used, study quality was assessed and trends were examined by regression. Results: Placebo groups of 43 studies published between 1988 and 2018 were included. The mean age at trial entry increased by 9.8 years per decade (95% confidence interval (CI): [2.7; 4.9]; p < 0.001). Mean baseline Expanded Disability Status Scale (EDSS) scores increased by 0.36 points (95% CI: [0.09; 0.62]; p = 0.009) and disease durations at baseline were prolonged by 1.8 years (95% CI: [0.7; 2.9]; p = 0.003) per decade. The trials became larger, specifically placebo groups increased by about 222 patients (95% CI: [36; 409]; p = 0.021) and 88 patients (95% CI: [12; 165]; p = 0.025) per decade for primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS), respectively. The proportion of patients on placebo experiencing disability progression within 24 months decreased by 7.6 percentage points (95% CI: [1.2; 14.1]; p = 0.022) per year. Conclusion: Over three decades, PMS trial populations changed and are now older, with a longer disease duration and more disability, with lower on-trial progression rates.

Toxicity in a double-blind, placebo-controlled pilot trial with D-penicillamine and metacycline in secondary progressive multiple sclerosis

1998 ◽  
Vol 4 (2) ◽  
pp. 74-78 ◽  
Author(s):  
B Dubois ◽  
M B D'Hooghe ◽  
K De Lepeleire ◽  
P Ketelaer ◽  
G Opdenakker ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Pilot Trial ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Tissue Type ◽  
Control Group ◽  
Double Blind ◽  
Gelatinase B ◽  
Double Blind Placebo ◽  
Secondary Progressive

The serine proteinase tissue-type plasminogen activator (t-PA) and the metalloproteinase gelatinase B (MMP-9) have recently been demonstrated in MS lesions. Both enzymes are interconnected in an enzyme cascade which contributes to destruction of the blood brain barrier and demyelination and both enzymes are inhibited by D-penicillamine. Metacycline was shown in in vitro experiments to inhibit gelatinase B. The combination of peroral D-penicillamine plus metacycline was evaluated in a double-blind placebo-controlled way in two groups of 10 patients suffering from secondary progressive multiple sclerosis. The major objectives of this pilot trial were to examine the safety of this combination and the possibility of blinding, while the effect on disease progression was considered as a secondary endpoint. Over a follow-up period of 1 year and in this selected patient group, there was no significant improvement in the Expanded Disability Status Scale score (EDSS) as compared with that of the placebo-control group. Toxicity was too high to consider additional trials with this combination of metalloproteinase inhibitors. Although peroral treatment is by most MS patients acknowledged as a major improvement in treatment compliance, one has to await the development of more selective and efficaceous protease inhibitors than those used in the combination therapy described here.

Development of cladribine treatment in multiple sclerosis

1996 ◽  
Vol 1 (6) ◽  
pp. 343-347 ◽  
Author(s):  
JC Sipe ◽  
JS Romine ◽  
JA Koziol ◽  
R McMillan ◽  
J Zyroff ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Course ◽  
Progressive Multiple Sclerosis ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Relapsing Remitting ◽  
History Of ◽  
New Type ◽  
Cns Demyelination

Cladribine is a new type of drug with properties of selective lymphocyte suppression that appear to favorably alter the clinical course of progressive multiple sclerosis (MS). The history of the development of cladribine treatment in chronic progressive MS is discussed, and the application of cladribine treatment to progressive multiple sclerosis in a double-blind, placebo crossover study is reviewed. Cladribine selectively targets both resting and dividing lymphocytes and may be able to destroy the activated lymphocytes that induce CNS demyelination, thus producing stabilization or improvement in chronic MS. Although the role of cladribine has not yet been fully defined, additional studies are underway to evaluate the efficacy and safety of cladribine in both progressive MS and relapsing-remitting MS.

scholarly journals Effects of Rivastigmine on Memory and Cognition in Multiple Sclerosis

2008 ◽  
Vol 35 (4) ◽  
pp. 476-481 ◽  
Author(s):  
Vahid Shaygannejad ◽  
Mohsen Janghorbani ◽  
Fereshteh Ashtari ◽  
Hamid Afshar Zanjani ◽  
Naser Zakizade
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Dysfunction ◽  
Clinical Symptoms ◽  
Placebo Response ◽  
Response To Treatment ◽  
Double Blind ◽  
Wechsler Memory Scale ◽  
Memory Score ◽  
The Mean ◽  
To Receive

Background:Cognitive dysfunction is one of the common clinical symptoms in multiple sclerosis (MS), but there is no effective treatment for it.Objective:The aim of this study was to evaluate the effect of rivastigmine in treating memory and cognitive dysfunction in MS.Methods:A single-center double-blind placebo-controlled randomized clinical trial conducted from October 2005 to February 2007. Sixty definite MS patients with cognitive impairment age 16 to 54 years were randomly allocated to receive a 12-week treatment course of either rivastigmine (1.5 mg once a day increment over 4 weeks to 3 mg twice daily) or placebo. Response to treatment was assessed by the Wechsler Memory Scale (WMS) at baseline and 12 weeks after start of therapy.Results:A slight, but significant memory improvement occurred in both groups. Of the 30 patients treated with rivastigmine, the mean (SD) WMS general memory score increased from 60.3 (4.2) at baseline to 64.9 (5.3) at the end of study period (P<0.001). Correspondingly, in the 30 patients treated with placebo, the mean (SD) WMS general memory score increased from 60.5 (4.9) to 64.5 (3.7) (P < 0.001). The average WMS general memory score at the end of trial did not changed between rivastigmine and placebo group (mean difference, 0.4; 95% CI, -2.0, 2.8).Conclusion:No significant differences were seen between rivastigmine and placebo on the mean (SD) WMS general memory score. A larger multicenter study of rivastigmine in MS is warranted in order to more definitely assess the efficacy of this intervention.

Hopelessness Ratings in Relapsing-Remitting and Secondary Progressive Multiple Sclerosis

2002 ◽  
Vol 32 (2) ◽  
pp. 155-165 ◽  
Author(s):  
Scott B. Patten ◽  
Luanne M. Metz
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Interferon Beta ◽  
Progressive Multiple Sclerosis ◽  
Double Blind ◽  
Exact Probability ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Trial Participants ◽  
Over Time

Objective: Two recent randomized double-blind placebo controlled clinical trials of interferon beta-1a in multiple sclerosis have obtained hopelessness ratings using the Beck Hopelessness Scale (BHS). One of these studies, the PRISMS trial, evaluated interferon beta-1a in relapsing remitting multiple sclerosis (RRMS). Another, the SPECTRIMS trial, evaluated the same medication in secondary progressive (SP) MS. The objective of this analysis was to compare levels of hopelessness in persons with RRMS and SPMS, and to describe changes over time in the clinical trial participants. Method: Raw data from each clinical trial was obtained from the sponsor of the trials (Serono). Median BHS ratings, and the proportions at or above the BHS cut-point of 10 were calculated over a two (PRISMS) or three (SPECTRIMS) year period. Results: The analysis included n = 532 clinical trial participants. Ratings of hopelessness were higher in SPMS clinical trial participants (SPECTRIMS) than in the RRMS group (PRISMS) at baseline (Fisher's exact test, p = 0.0035). Furthermore, ratings of hopelessness were higher during follow-up than at baseline, in the SPMS group (McNemar's exact probability, p = 0.0015), but not in the RRMS group (McNemar's exact probability, p = 0.65). Depression was strongly associated with hopelessness in both RRMS ( z = 4.13, p < 0.001) and SPMS ( z = 5.24, p < 0.001). Conclusions: Hopelessness is associated with SPMS, and may increase over time in this group. Hopelessness may influence suicide risk in people with MS and may potentially have an impact on coping and quality of life. Additional research is necessary to define the clinical implications of hopelessness in persons with this condition.

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