U. Baumhackl and S. Fördermair. Enzymtherapie bei Multipler Sklerose. Allgemeinmedizin 19 (4):169-172, 1990.
Any promising therapeutic concept in multiple sclerosis (MS) requires an individual form of therapy dependent on the course of the disease, the actual symptoms, and the local treatment facilities available in the hospital or at home with or without the support of the family. These different factors, the variable course of the disease and the severity and localization of the dysfunction all determine the degree of impairment of the MS patient. The cause of MS remains unknown, but there is some knowledge about the pathogenic factors and this is where the therapy trials begin – for the acute episode and to try to halt the progression of the disease. However, our success is so far unsatisfactory. A potential form of therapy is described that is based on the clinical experience of individual physicians and on the elimination of circulating immune complexes. A multicentre trial was set up for further evaluation. Our initial experience is communicated ona preliminar basis after an observation period of less than 1 year. So far, we can only comment on the acceptance safety of enzyme therapy in MS.

U. Baumkackl. Ergebnisse einer Pilotstudie zur Verabreichung eines oralen Enzympräparates bei multipler Sklerose. In: Systemische Enzymtherapie: Aktueller Stand und Fortschritte, edited by H. Wrba, H. W. Kleine, K. Miehlke, F.-W. Dittmar, and E. R. Weissenbacher, München:Medizin Verlag, 1996, p. 203-210. (abstract not available)

Baumhackl U, Kappos L, Radue EW, Freitag P, Guseo A, Daumer M, and Mertin J. A ran, double-blind, placebo-controlled study of oral hydrolytic enzymes in relapsing multiple sclerosis. Mult Scler. 11 (2):166-168, 2005.
Oral administration of hydrolytic enzymes (HE), such as bromelain, trypsin and rutosid, may have beneficial effects on the clinical course of neurological symptoms related to multiple sclerosis (MS). This is supported by a complete protection by HE from experimental allergic encephalomyelitis, an animal model related to MS. Three hundred and one patients with relapsing MS were enrolled in a double-blind, placebo-controlled trial. No treatment effect between the placebo and the HE groups was found either for clinical or MRI parameters

H. Krejcová. Wobenzym® and Wobe-Mugos® in the Treatment of Multiple Sclerosis. Wirksamkeit und Verträglichkeit Studien-Nr.: MU-90203Randomisierte Parallelgruppenstudie gegen KortikoidtherapieIntegrierter biometrisch-medizinischer Abschlußbericht gemäß FDA- und CPMP-Richtlinien, 2003
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) e_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).

J. Mertin, G. Stauder, and and the Esems Working Group. Use of oral enzymes in multiple sclerosis patients. Int J Tissue Reac 19 (1/2):95, 1997
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 1998. In case the enzymes prove to be superior over placebo a safe and inexpensive therapy in the management of MS would be available

Mialovyts’ka OA. [Effect of phlogenzym in long-term treatment of patients with multiple sclerosis] Lik Sprava. 2003 Apr-Jun;(3-4):109-13. [Article in Ukrainian]
An assessment was carried out of clinical effectiveness of the drug phlogenzym in 74 patients with remitting, remitting-progressive, and secondary progressive course of multiple sclerosis. Phlogenzym intake for up to one to three years resulted in decline in the incidence of complications, with their degree having come to be lower, duration of remissions longer, progression of the illness slowed down. The data secured suggest to us that phlogenzym is a safe agent. It can, we believe used in a therapeutic regimen for those patients presenting with remitting and remitting-progressive types of the course of the disease

C. Neuhofer. Enzymtherapie bei Multipler Sklerose. Hufeland-Journal 2:47-50, 1986.
In summary, we can thus speak of a delightful result, especially when we consider the problematic nature of this disease. I have given a report dealing 150 patients showing 150 different symptoms, courses of illness and fates; 150 patients for whom other therapy tests proved to be a failure and who were able to achieve an essential improvement by means of the enzyme therapy.
For all these reasons it seemed to be important to me to inform you about this experience I gained. By means of this therapy you might be able to give to a large number of patients both relief of troubles and hope for future.

Neuhofer C.  Pathogenic immune complexes in MS: their elimination by hydrolytic enzymes. A therapeutic approach. International Multiple Sclerosis Conference. Rome, Italy, 1988.  International Multiple Sclerosis Conference.Rome, Italy, 1988., 1988. (abstract not available)

Page SA, Verhoef MJ, Stebbins RA, Metz LM, Levy JC.The use of complementary and alternative therapies by people with multiple sclerosis. Chronic Dis Can. 2003 Spring-Summer;24(2-3):75-9.
Complementary and alternative medicine (CAM) refers to therapeutic approaches not considered part of conventional medicine. A survey was mailed to sample of patients with multiple sclerosis (MS). The response rate was 440/673 (65%). Mean sample age was 48 years; 75% were female. Respondents ranged from mildly to severely impaired. Seventy percent used CAM primarily to improve health and manage the symptoms of MS. Most consumers reported positive effects. Lack of knowledge was the most common reason given for not using CAM. Patient education, physician-patient dialogue, and continued research and regulation of CAM are important to the well being of CAM consumers
Shinto L, Calabrese C, Morris C, Sinsheimer S, Bourdette D.Complementary and alternative medicine in multiple sclerosis: survey of licensed naturopaths. J Altern Complement Med. 2004 Oct;10(5):891-7.

van-der-Ploeg,-H-M; Molenaar,-M-J; van-Tiggelen,-C-W Gebruik van alternatieve behandelwijzen door patienten met multipele sclerose. [Use of alternative treatments by patients with multiple sclerosis] Ned-Tijdschr-Geneeskd. 1994 Feb 5; 138(6): 296-9
OBJECTIVE. Survey on the use of alternative treatments by patients with multiple sclerosis (MS). SETTING. Vrije Universiteit Amsterdam. DESIGN. Descriptive. METHOD. A structured telephone interview was conducted with 100 MS patients randomly selected from the membership list of the Dutch Multiple Sclerosis Society. RESULTS. At the time of the survey 26% of the 88 respondents reported current use of alternative treatments. An additional 42% reported use of alternative treatments in the past, but had ceased to take them. The currently most frequently used treatment was homeopathy followed by vitamin treatments, paranormal treatments and phytotherapy. The treatments most used in the past were paranormal treatments, homeopathic remedies and enzyme therapy. Recommendations by friends and relatives were strong incentives to start alternative treatment. Patients ceased using these treatments when the treatments proved ineffective. In general, the current users of alternative treatments had a favourable impression of their alternative therapist. CONCLUSION. When compared with patients with other chronic diseases, the use of alternative treatments by MS patients is high.

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