Multiple sclerosis patients treated with Wobenzym showed a decreased
number of attacks and a shortened duration of those fewer
attacks that did occur. The studies conclude that the
stabilization of the nervous
system and the improved activities of daily living were a
direct result of the decreased inflammatory activity
due to use of Wobenzym.
From FREQUENTLY ASKED QUESTIONS, with answers by Joseph J Collins, RN, ND
Read the special section: : Controlling Systemic Inflammation with Systemic Enzyme Support
What the literature says about Systemic Enzyme Support and:
of oral enzymes in multiple sclerosis patients.
Mertin J.1, Stauder G.2, ESEMS working group3.
Use of oral enzymes in multiple sclerosis patients. Inter. Journal
of Tissue Reactions 1997, Vol. XIX , No.1/2, pp 95
Abstract: In 1986, a first report on a cohort of 300 multiple
sclerosis (MS) patients treated with hydrolytic enzymes describes
stabilizing of the disease and reduction of the relapse rate. These
findings have been supported by case reports and by subjective
patient reports. Soon it became clear that a stepwise approach was
necessary, in order to prove whether oral enzymes are effective and
safe in MS. As first step an open multicentric study was performed.
An evaluation of the data showed hydrolytic enzymes to stabilize the
neurological impairment and to improve activities of daily living.
Now a randomized, prospective, double-blind, placebo-controlled
study according to the European GCP-guidelines is going on. 300
patients from 23 European centres are included to randomly receive
Phlogenzym or placebo in a daily dose of 3 tablets b.i.d. or 2
tablets t.i.d. over a period of 2 years. Progression rate, relapse
rate, neurological signs and symptoms (incl. MRI), emotional status
and unwanted side effects are main endpoints. Some have already
finished the treatment period. Results of that study will be
available in early 1999. In case the enzymes prove to be superior
over placebo a safe and inexpensive therapy in the management of MS
would be available.
Poster Reference Number 53.
Wobenzym® and Wobe-Mugos® in the Treatment of
Hana Krejcová. Wobenzym® and
Wobe-Mugos® in the Treatment of Multiple Sclerosis.
PharmaScript, Kathi-Kobus-Steig 1, D-82515 Wolfratshausen,
Summary: In this open randomised clinical phase III trial (acc. to
German Drug Law) with two parallel groups, efficacy and tolerance of
two enzyme drugs were tested in patients with multiple sclerosis:
during acute attacks, Wobenzym® tablets (high dose) and
Wobe-Mugos® ampoules were used, in the interval low dose
Wobenzym® tablets. This was compared with a treatment
with ACTH/corticosteroids during attacks and - in patients with
worse prognosis and in advanced stages if necessary cyclophosphamid
in the interval.
40 patients with established multiple sclerosis (clinical follow-up, liquor diagnosis, MRI, CT and/or VEP, optional SPECT) were taken into this study. 20 patients received the enzyme preparations and 20 ACTH/corticosteroids. The data of all patients were evaluable.
The study was conducted under the direction of Prof. MUDr. Hana Krejcová, DrSc., Neurologická klinika, Pediatrická Fakulta, Universita Karlova, FN Motol, V úvalu 84, 15012 Praha 5, Czech Republic.
In any case the therapy in the enzyme group started with high dose enzymes:
during the first week the patients received 1 ampoule Wobe-Mugos® pro inj. and 30 tablets of Wobenzym® daily. In the second week the patients got 1 ampoule Wobe-Mugos® every other day and 30 tablets of Wobenzym® daily. From the third week the patients received a maintenance dose of 9 tablets Wobenzym® each day.
The patients in the comparative group received throughout an attack either a pulsed therapy of high dose corticosteroids (3 days 1000 mg/die methylprednisolone i.v., 2 days pause, 3 days tapering off), an oral therapy with corticosteroids (60 - 80 mg/die methylprednisolone orally 2 to 4 weeks, last week tapering off) or a therapy with ACTH (100 1.E. ACTH daily during 2 weeks, last week tapering off). During intervals patients with worse prognosis and/or advanced stages got daily if necessary 3 mg/kg body weight oral cyclophosphamide. Patients with good prognosis and in early stage received no interval therapy.
The patients were comparable at baseline with regard to age, sex, family case history, classification of multiple sclerosis by Poser, kind of disease, parameters of the functional system, of the performance system and of the social environment (Wilcoxon-Mann-Whitney- U-Test: p > .05).
The main endpoint for statistical evaluation was the extended Kurtzke disability scale (EDSS).
Despite randomisation, the patients had a significantly different mean value at baseline (enzyme group: 3.3 - corticosteroid group: 4.5 - p = .015). After adjusting the baseline values of either group to 100%, a statistically significant difference in favor of the enzymes was demonstrated from the sixth month (p < .01 ), an even highly significant difference at end of therapy (p < .001 ).
If the difference at baseline is judged as clinically so relevant that a direct comparison during the course of the therapy is not acceptable, there is nevertheless a difference in favor of the enzymes in the change of the Kurtzke scale: whereas the value improved until the last available vaIue in the enzyme group by 24.2% (from 3.3 to 2.5), it worsened in the corticosteroid group by (-)2.2% from 4.5 to 4.6.
As secondary criteria the parameters of the functional system, of the performance system and of the social environment, the serodiagnosis, the diagnosis of the liquor, and the subjective judgement of efficacy and tolerance were evaluated statistically.
The parameters of the functional system (the findings of the pyramidal tract, cerebellum, sensorium, vesicorectal function, index of the gait pattern, sum score), of the performance system (dress and undress, personal hygiene, fatigability,) and of the social environment (work, sumscore) showed statistically significant (p < .05) differences at end of therapy in favor of the enzymes. The data of the parameter"walking" and of the parameters of the social envorinment showed significant advantages in the corticosteroid group.
There were other statistically significant differences in favor of the enzyme treatment for the number of hospitalisation and for the number and duration of multiple sclerosis attacks: there was a total of 15 hospitalisations necessary in the enzyme group (mean 0.8 hospitalisations per patient) and 35 hospitalisations in the corticosteroid group (mean 1.8 - p = .038). The mean duration of hospitalisation (enzymes: 25.7 days, corticosteroids: 60.7 days) just missed significance (p = .055). 15 attacks were documented in the enzyme group (mean 0.8 attacks per patient) with a mean duration of 28.7 days, 37 attacks in the corticosteroid group (mean 1.9 - p - .019) with a mean duration of 58.2 days (p = .02). There were no differences in progression and severity of the attacks between the groups (p > .05).
The result of the therapy was judged by the physician and by the patients at end of therapy as 3.1 ("slight improvement") in the enzyme group and as 4.1 ("unchanged") in the corticosteroid group. The groups differed statistically significantly in favor of the enzyme treatment (p < .05).
The judgement of efficacy by the physician was 2.0 ("good') and by the patients 2.1 ("good") in the enzyme treated group and 3.1 ("moderate") in the corticosteroid group. The difference was statisticalIy significant in favor of the enzymes (p < .05). The tolerance of the treatment was judged by the physician and by the patients as 1.4 ("very good" to "good") in either group. The duration of treatment was comparable in both groups. The average duration was 19.4 months in the enzyme group and 23.0 months in the corticosteroid group. The difference was not significant (p > .05).
Three "moderate" adverse events in two patients (gastro-intestinal symptoms and cholecystitis, transient increase of transaminases) were documented in the enzyme group. The gastro-intestinal symptoms started during the 12th month, the cholecystitis during the 15th month, but they were "certainly not" caused by the enzymes. The increase of transaminases started during the tenth month. As there was not found any causa, the relationship to the enzyme therapy was judged as "probably". The enzymes were discontinued in the first patient after the second adverse event, in the second patient immediately. No sequelae were documented.
There were no adverse events noted in the corticosteroid group. The difference was not significant (p = .605).
Poster Reference Number 54.
of oral enzymes in multiple sclerosis: phenotyping of peripheral
blood lymphocytes from MS patients under long-term treatment with
orally administered hydrolytic enzymes.
Stauder G.,1 Donnerstag B.,2 Baumhackl U.,3
Buschmans E.1. Use of oral enzymes in multiple sclerosis:
phenotyping of peripheral blood lymphocytes from MS patients under
long-term treatment with orally administered hydrolytic enzymes.
Inter. Journal of Immunotherapy 1997, Vol. XIII, No. 3/4, pp
135-137, ISSN 0255-9625 SO 112 (19-04-2) - (18-00-2)
1Mucos Pharma, Clinical Research, Geretsried, Germany, 2Dept. of Biological Chemistry, University Medical Center, Frankfurt/Main, Germany, 3Dept. of Neurology, District Hospital, St.Pölten, Austria.
Summary: Oral hydrolytic enzymes in combination with rutosid have
been applied in MS patients for more than 20 years. We investigated
whether immunological alterations in MS patients are influenced by
enzyme treatment. We determined the phenotypes of specific
lymphocytic antigens in 12 patients with relapsing-remitting MS, who
were known to be under long-term treatment with oral hydrolytic
enzymes (Phlogenzym®). Matched untreated (i.e., only treated for
symptoms) MS patients (n=18) and healthy volunteers (n=10) served as
For phenotyping, the following lymphocytic antigens were measured: CD4, CD8, CD3, CD2, CDl9, CD56, CDl4, CD45, CD45RA, CD45RO, CD25, CD54 and HLA-DR. Tests were carried out with a panel of different fluorescence-conjugated murine monoclonal antibodies and subsequent two color flow-cytometry. Data is expressed as percentage gated cells. Symptomatically treated patients had increased CD4, CD19, CD2 and CD45RO, CD54 and CD56. These changes were influenced by hydrolytic enzymes in the following manner: CD8 was markedly decreased; CD4, CD2, CD25, CD-45-RO, CD-45RA, CD56 slightly decreased. Furthermore, a statistically significant decrease was found for CD45 and CD54. From these results the conclusion can be drawn that positive clinical findings in MS patients under oral hydrolytic enzymes are causatively linked to a decrease in inflammatory activity.
Poster Reference Number 55.