A novel therapeutic approach for multiple sclerosis: Preliminary results of the Israeli linomide, double-blind placebo controlled study in secondary progressive M.S. with monthly MRI evaluation

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.

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The European Study on Enzyme Therapy in Multiple Sclerosis (ESEMS): results of a multicentre, randomized, double-blind, placebo-controlled study

Multiple Sclerosis ◽

10.3109/9780203212974-50 ◽

2001 ◽

pp. 419-425

Keyword(s):

Multiple Sclerosis ◽

Controlled Study ◽

Enzyme Therapy ◽

European Study ◽

Double Blind ◽

Double Blind Placebo

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Treatment of relapsing-remittent multiple sclerosis with recombinant human interferon-alfa-2a: design of a randomised, placebo-controlled, double blind trial in Norway

Multiple Sclerosis Journal ◽

10.1177/135245859600100618 ◽

1996 ◽

Vol 1 (6) ◽

pp. 372-375 ◽

Cited By ~ 4

Author(s):

H Nyland ◽

K-M Myhr ◽

F Lillås ◽

AI Smievoll ◽

T Riise ◽

...

Keyword(s):

Multiple Sclerosis ◽

Primary Objective ◽

Interferon Alfa ◽

Controlled Study ◽

Human Interferon ◽

New Disease ◽

Efficacy And Safety ◽

Double Blind ◽

Double Blind Placebo ◽

Drug Free

A multicentre, randomised, double-blind, placebo controlled study to evaluate the efficacy and safety of 4.5 and 9.0 MIU recombinant human interferon alfa-2a (Rof eron-A™) given thrice weekly in patients with relapsing-remittent multiple sclerosis is described. The patients are treated for 6 months followed by a 6 months drug-free period. The primary objective is to determine new disease activity analysed by monthly MRI with gadodiamide (GdDTPA-BMA, Omniscan™). The study is conducted at eight centers in Norway and is completed in January 1996.

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Treatment of spasticity with repetitive magnetic stimulation; a double-blind placebo-controlled study

Multiple Sclerosis Journal ◽

10.1177/135245859600200503 ◽

1996 ◽

Vol 2 (5) ◽

pp. 227-232 ◽

Cited By ~ 63

Author(s):

Jorgen F Nielsen ◽

Thomas Sinkjaer ◽

Johannes Jakobsen

Keyword(s):

Multiple Sclerosis ◽

Stretch Reflex ◽

Magnetic Stimulation ◽

Controlled Study ◽

Double Blind ◽

Double Blind Placebo ◽

Future Studies ◽

Sham Stimulation ◽

Repetitive Magnetic Stimulation ◽

Reflex Threshold

The effect of repetitive magnetic stimulation on spasticity was evaluated in 38 patients with multiple sclerosis in a double-blind placebo-controlled study. One group was treated with repetitive magnetic stimulation (n=2l) and the other group with sham stimulation (n=l7). Both groups were seated twice daily for 7 consecutive days. Primary end-points of the study were changes in the patients self-score, in clinical spasticity score, and in the stretch reflex threshold. The self-score of ease of daily day activities improved by 22% (P=0.007) after treatment and by 29% (P=0.004) after sham stimulation. The clinical spasticity score improved 3.3±4.7 arbitrary unit (AU) in treated patients and 0.7±2.5 AU in sham stimulation (P-0.003). The stretch reflex threshold increased 4.3±7.5 degls in treated patients and-3.8±9.7 degls in sham stimulation (P=0.001). The data presented in this study supports the idea that repetitive magnetic stimulation has an antispastic effect in multiple sclerosis. Future studies should darify the optimal treatment regimen.

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