SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
All tested variables showed a tendency in favor for Wobe-Mugos E therapy as addition to standard therapy. Enzymes improve the quality of life by reducing cancer disease typical symptoms, they reduce side effects of chemo-/radiotherapy and they have a potential of prolonging life (preliminary data only).
Bacterial enzymes are antineoplastic perspective agents in oncology. Current strategy of tumor enzyme therapy is primarily based on the strictly defined differences of biochemical properties between normal and tumor cells and more precisely on their different sensitivity to deficit of essential growth factors, including amino acids. The growth inhibitory effects of three bacterial enzymes: glutamine (asparagin)ase, methionine gamma-lyase and lysine alpha-oxidase were demonstrated in in vitro and in vivo using several tumor lines. These results suggest that commercial production of certified standard enzyme preparations and their knowledge-based rational application will provide a new potent anti-tumor preparations employed in oncology.
Systemic enzyme therapy represents a special therapeutic approach consisting in the oral application of high doses of hydrolytic animal and plant enzyme combinations. The originally empirical method was by detailed experimental analyses and successful clinical studies transformed into a widely appreciated therapeutic method of various pathologic processes. In spite of this fact systemic enzyme therapy has been repeatedly questioned by referring to an almost hundred year old dogma claiming the unabsorbality of enzymes in the macromolecular form. The authors present arguments denying the unexceptional validity of this dogma. The histological, radiological, biochemical (chromatographical, enzymological), immunological and biological methods have convincingly proven that a part of swallowed enzymes may pass the intestinal barrier in an undamaged macromolecular form and realize their activities in the body. The most important elements able to absorb macromolecules seem to be so called "M-cells" (FAE) which cover lymphoid foci of the organized gut lymphoid tissue. Other mechanisms of enzyme resorption are under discussion. The absorbed enzymes are rapidly complexed with naturally occurring blood antiproteases. In these complexes the potential immunogenicity of enzymes is restricted and they are concentrated into pathologically affected areas of the body. Complexes in addition display important immunoregulatory activities.
Non-specific enzyme therapy does not intend the catalysis of definite steps of metabolism, but claims to stimulate regenerative processes in general. Initially, non-specific enzyme therapy had been considered to be a promising approach. The growing knowledge in basic research and the lack of evidence for clinical effectiveness rendered the predominantly oral application of enzyme preparations for non-specific treatment outdated by the 1960s. In Germany, however, the absence of strict legal regulations prevented the deregistration of drugs designed for non-specific enzyme therapy. Furthermore, numerous clinical studies were initiated by the leading producer of enzyme preparations in Germany in order to provide the scientific confirmation missing so far. Our critical and systemic review of the published trials shows that neither the mechanism of action could be enlightened, nor the clinical benefit of non-specific enzyme therapy proven on an acceptable level of scientific standards.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Enzyme therapy has altered forever the management of patients with Gaucher disease. Studies in over 1200 treated Gaucher disease patients have demonstrated regression of hepatic, splenic, bony and haematological abnormalities, with a return towards health in many affected patients. The therapy is well tolerated, with approximately 7% of patients having adverse effects. However, the lack of standardised clinical staging and tracking procedures, and a poor understanding of the basic biochemistry and cell biology of the administered enzyme, continue to inhibit optimisation of treatment. Ultimately, preventive intervention with enzyme therapy will require absolute safety and much less expensive preparations, and accurate predictive genotype testing to fully optimise this mode of therapy. The success and pitfalls encountered in enzyme therapy for Gaucher disease provide a map for the development of such therapies for other inborn errors of metabolism.
Explore the source record for details and available documents.
Enzyme replacement therapy for the lysosomal storage disorders derives its impetus from the successes achieved in the treatment of Gaucher disease. After nearly two decades of persistent but unsuccessful efforts, the promise of therapy through enzyme replacement was losing credibility. Then, the fortunate intersection of two different lines of scientific research produced the necessary breakthrough. The dramatic responses to enzyme replacement therapy in patients with Gaucher disease made it immediately clear that this treatment approach was a success. Furthermore, the large number of patients with the disorder guaranteed commercial involvement. The lessons learned from the development of enzyme replacement therapy for Gaucher disease are broadly applicable to other lysosomal storage diseases and will be reviewed in this paper.
Plant extracts with a high content of proteolytic enzymes have been used for a long time in traditional medicine. Besides proteolytic enzymes from plants, 'modern' enzyme therapy additionally includes pancreatic enzymes. The therapeutic use of proteolytic enzymes is partly based on scientific studies and is partly empirical. The aim of the current review is to provide an overview of clinical trials of systemic enzyme therapy in oncology, and to discuss the evidence for their possible mechanisms of action. Clinical studies of the use of proteolytic enzymes in oncology have mostly been carried out on an enzyme preparation consisting of a combination of papain, trypsin and chymotrypsin. This review of these studies showed that enzyme therapy can reduce the adverse effects caused by radiotherapy and chemotherapy. There is also evidence that, in some types of tumours, survival may be prolonged. The beneficial effect of systemic enzyme therapy seems to be based on its anti-inflammatory potential. However, the precise mechanism of action of systemic enzyme therapy remains unsolved. The ratio of proteinases to antiproteinases, which is increasingly being used as a prognostic marker in oncology, appears to be influenced by the oral administration of proteolytic enzymes, probably via an induction of the synthesis of antiproteinases. Furthermore, there are numerous alterations of cytokine composition during therapy with orally administered enzymes, which might be an indication of the efficacy of enzyme therapy. Effects on adhesion molecules and on antioxidative metabolism are also reviewed.
OBJECTIVE: Enzyme therapy based on animal digestive extracts was investigated as a means of completely digesting toxic residues from gluten in the small intestine, thus providing a means of protection of the mucosa. MATERIAL AND METHODS: A randomized, placebo-controlled, clinical trial of an encapsulated enzyme extract was conducted in 21 coeliac patients in remission who were challenged with a modest amount of gluten daily over 2 weeks. Enzyme extract (900 mg) in three divided doses was administered during this challenge to half the group and a placebo to the other half in a double-blind, crossover design. Symptoms were recorded in daily diaries; blood was taken for tissue transglutaminase antibodies (anti-tTG) at the start and at intervals up to 12 weeks. Duodenal biopsies were performed for histological assessment at the start and end of each challenge period for 6 patients chosen at random from volunteers. After a further 10 weeks, the groups were changed over, and the same assessments carried out. RESULTS: Only 8 of the 21 patients (38%) had more than 5 episodes of moderate to severe symptoms during either of the gluten challenge periods, and in these, symptoms scores were ameliorated during enzyme therapy compared with the placebo period (p<0.02). Rises of 5 U/ml or more in anti-tTG occurred in only 5 patients at about 6-8 weeks after challenge, but were not correlated with symptoms. CONCLUSIONS: Only 1 of the 6 patients had normal histology at entry, thus focusing attention on the need for better management of the disease. By histological criteria, enzyme therapy offered better protection than placebo during the gluten challenges. The study supports the use of enzyme supplementation as a safeguard for patients with coeliac disease because of the difficulty of ensuring a strictly gluten-free diet.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The clinical impact of neutralizing antibodies directed against the therapeutic enzyme was investigated in patients with Gaucher disease. Two patients with Gaucher disease type 1 were followed for their clinical progression during antibody development and clinical changes during tolerization. Patient 1 developed neutralizing antibodies to imiglucerase (GCase) at the 10th month of enzyme therapy. Tolerization was achieved within a 42-month period with a short course of cyclophosphamide and then higher dose enzyme (60 IU/kg/week) alone. Patient 1 continues to improve up to 100 months of enzyme therapy despite the presence of low level in vitro neutralizing antibodies. Patient 2 developed neutralizing antibodies to GCase at the 29th month of enzyme therapy that correlated with clinical deterioration. Clinical stabilization has been observed with increased enzyme therapy (60 IU/kg/week) even in the presence of the neutralizing antibodies. Patient 2 is the first to develop neutralizing antibodies after 12 months of enzyme therapy. Plasma chitotriosidase activities were not well correlated with the clinical course in either patient. The presence of neutralizing antibodies should be suspected in Gaucher disease patients on enzyme therapy who experience diminished response or deterioration. The persistence of minimal amounts of in vitro neutralizing antibodies does not interfere with the therapeutic effectiveness. Chitotriosidase is not a sensitive marker for the severity of disease or disease progression.