Therapeutic Enzymes Used for the Treatment of Cardiovascular Diseases and Coagulation Disorders

2018 ◽  
pp. 23-45
Author(s):  
Abderrezak Khelfi
Keyword(s):  
Cardiovascular Diseases ◽  
Blood Clot ◽  
Hereditary Diseases ◽  
Coagulation Disorders ◽  
Recombinant Enzymes ◽  
Enzyme Preparations ◽  
Enzyme Replacement ◽  
Key Factor ◽  
Foreign Proteins ◽  
Therapeutic Enzymes

The successful introduction of enzyme replacement therapy opened the way for the use of enzymes, first as crude preparations and later as highly purified enzymes for use in cardiovascular diseases, clotting disorders, etc. Elimination of blood clot is the key factor in thrombolytic therapy and fibrinolytic enzyme therapy can be practiced to remove the clot. Based on the mechanism of action, they are of two types of enzymes: plasminogen activators and plasmin-like enzymes. Plasma products are usually employed as a source of several enzymes used for the treatment of coagulation disorders. While these products have traditionally been purified from blood donations and obtained as foreign proteins obtained from heterogeneous sources, most are now produced by biotechnology. The therapeutic enzymes reviewed in this chapter are used for the treatment of cardiovascular diseases and hereditary diseases leading to coagulation disorders. Enzyme preparations obtained by direct fractionation from a naturally producing source and recombinant enzymes are considered in this chapter.

Enzyme Replacement Therapy

2018 ◽  
pp. 1-22
Author(s):  
Abderrezak Khelfi
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Lysosomal Storage ◽  
Enzyme Preparations ◽  
Enzyme Replacement ◽  
Therapeutic Uses ◽  
Enzyme Defects ◽  
Biological Sources ◽  
Therapeutic Enzymes ◽  
Deficiency Diseases

Enzyme replacement therapy is a therapeutic approach in which the specific enzyme that is absent or inactive in affected individuals is replaced with a functional enzyme molecule derived from biological sources or produced by biotechnology. A large number and variety of enzyme defects have been identified in humans. Over 40 hereditary deficiency diseases were reported. The common feature is that enzyme deficiency leads to the accumulation of undegraded molecules and lysosomal storage, resulting in organ dysfunction. Crude enzyme preparations are often unsuitable for therapeutic uses because of their potential contamination and antigenicity. Advances in gene identification and cloning led to the subsequent production and demonstration of equal efficacy of recombinant human enzyme. The adverse events recorded range from boxed warnings for severe allergic reactions. This chapter summarizes therapeutic enzymes used in clinical practice, with particular reference to those obtained from biological sources and biotechnology processes.

Nanodrugs as a new approach in therapy of cardiovascular diseases and cancer with tumor-associated angiogenesis

2020 ◽  
Vol 28 ◽  
Author(s):  
Justyna Hajtuch ◽  
Karolina Niska ◽  
Iwona Inkielewicz-Stepniak
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Controlled Drug Release ◽  
Biological Properties ◽  
Comprehensive Information ◽  
Conventional Drug ◽  
Key Factor ◽  
Functionalized Materials

Background: Cancer along with cardiovascular diseases are globally defined as leading causes of death. Importantly, some risk factors are common to these diseases. The process of angiogenesis and platelets aggregation are observed in cancer development and progression. In recent years, studies have been conducted on nanodrugs in these diseases that have provided important information on the biological and physicochemical properties of nanoparticles. Their attractive features are that they are made of biocompatible, well-characterized and easily functionalized materials. Unlike conventional drug delivery, sustained and controlled drug release can be obtained by using nanomaterials. Methods: In this article, we review the latest research to provide comprehensive information on nanoparticle-based drugs for the treatment of cancer, cardiovascular disease associated with abnormal haemostasis, and the inhibition of tumorassociated angiogenesis. Results: The results of the analysis of data based on nanoparticles with drugs confirm their improved pharmaceutical and biological properties, which gives promising antiplatelet, anticoagulant and antiangiogenic effects. Moreover, the review included in vitro, in vivo research and presented nanodrugs with chemotherapeutics approved by Food and Drug Administration. Conclusion: By the optimization of nanoparticles size and surface properties, nanotechnology are able to deliver drugs with enhanced bioavailability in treatment of cardiovascular disease, cancer and inhibition of cancer-related angiogenesis. Thus, nanotechnology can improve the therapeutic efficacy of the drug, but there is a need for a better understanding of the nanodrugs interaction in the human body, because this is a key factor in the success of potential nanotherapeutics.

scholarly journals Glycosylation and functionality of recombinant β-glucocerebrosidase from various production systems

2013 ◽  
Vol 33 (5) ◽  
Author(s):  
Yoram Tekoah ◽  
Salit Tzaban ◽  
Tali Kizhner ◽  
Mariana Hainrichson ◽  
Anna Gantman ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Production Systems ◽  
In Vivo Studies ◽  
Target Cells ◽  
Enzyme Replacement ◽  
Target Organs ◽  
Key Factor ◽  
Cell Stability ◽  
Mannose Receptors

The glycosylation of recombinant β-glucocerebrosidase, and in particular the exposure of mannose residues, has been shown to be a key factor in the success of ERT (enzyme replacement therapy) for the treatment of GD (Gaucher disease). Macrophages, the target cells in GD, internalize β-glucocerebrosidase through MRs (mannose receptors). Three enzymes are commercially available for the treatment of GD by ERT. Taliglucerase alfa, imiglucerase and velaglucerase alfa are each produced in different cell systems and undergo various post-translational or post-production glycosylation modifications to expose their mannose residues. This is the first study in which the glycosylation profiles of the three enzymes are compared, using the same methodology and the effect on functionality and cellular uptake is evaluated. While the major differences in glycosylation profiles reside in the variation of terminal residues and mannose chain length, the enzymatic activity and stability are not affected by these differences. Furthermore, the cellular uptake and in-cell stability in rat and human macrophages are similar. Finally, in vivo studies to evaluate the uptake into target organs also show similar results for all three enzymes. These results indicate that the variations of glycosylation between the three regulatory-approved β-glucocerebrosidase enzymes have no effect on their function or distribution.

A biochemical and physicochemical comparison of two recombinant enzymes used for enzyme replacement therapies of hunter syndrome

2014 ◽  
Vol 31 (4) ◽  
pp. 309-315 ◽  
Author(s):  
Yo Kyung Chung ◽  
Young Bae Sohn ◽  
Jong Mun Sohn ◽  
Jieun Lee ◽  
Mi Sun Chang ◽  
...  
Keyword(s):  
Hunter Syndrome ◽  
Recombinant Enzymes ◽  
Enzyme Replacement

scholarly journals Pancreatology: debunked myths

2020 ◽  
Vol 48 (3) ◽  
pp. 44-53
Author(s):  
N. B. Gubergrits ◽  
N. V. Byelyayeva
Keyword(s):  
Chronic Pancreatitis ◽  
Replacement Therapy ◽  
Pancreatic Insufficiency ◽  
Exocrine Pancreatic Insufficiency ◽  
Overweight And Obesity ◽  
Evidence Based ◽  
Enzyme Preparations ◽  
Enzyme Replacement ◽  
European Guidelines ◽  
Relieve Pain

Enzyme replacement therapy is not always effective enough upon exocrine pancreatic insufficiency. One of the main reasons is myths — doctors’ misconceptions about the indications and rules of replacement therapy. In particular, there is an outdated opinion about the effectiveness of tablet enzyme preparations used for the relief of pancreatic pain. However, a number of evidence-based studies have proved that enzyme preparations are not effective enough to relieve pain in chronic pancreatitis, and thus should not be used for this purpose. This statement is recorded in the United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis, as well as in the recommendations of the American College of Gastroenterology. In addition, tablet preparations are characterized by asynchronism of the passage of the chyme and the tablet along the digestive tract. The second myth is that drugs without an acid-resistant coat start hydrolyzing the components of the chyme in the stomach, which ensures higher efficiency as compared to Creon. But in the absence of a coat, enzymes are inactivated in the acidic environment of the stomach and cannot have any effect at all. The third myth is that enzyme preparations always cause constipation. In fact, constipation occurs in no more than 10% of cases. They are usually associated with an overdose of the drug, concomitant pathology or insufficient compliance. The fourth myth is that prescribing the doses of enzyme preparations indicated in the European Guidelines causes addiction. It is crucial to know that such doses do not exceed 10% of the pancreas’s own capacities, therefore, they cannot significantly affect these capabilities, which is also demonstrated by evidence-based studies. The fifth myth is that patients gain weight because of enzyme preparations, and they should not be prescribed upon overweight and obesity. Numerous data firmly show that pancreatic insufficiency often occurs in such cases, and enzyme preparations are required. The sixth myth is that a drug with a different composition can be produced under the usual established product name. For example, NEO is added to the name to “mask” a drug with a new composition. Doctors should carefully monitor the composition of such drugs. The seventh myth is that a minimicrospherical preparation (Creon) is as effective as microspherical preparation. However, this statement turned out to be a myth as well. Minimicrospherical preparations are proved to be significantly more effective in clinical practice. Thus, the above-mentioned myths, like many others, are based on insufficient knowledge in the field of pancreatology.

scholarly journals Differentiated approach to replacement therapy in exocrine pancreatic insufficiency

2020 ◽  
Vol 47 (2) ◽  
pp. 37-49
Author(s):  
N. B. Gubergrits ◽  
N. V. Byelyayeva ◽  
A.Ye. Klochkov ◽  
G. M. Lukashevich ◽  
P. G. Fomenko
Keyword(s):  
Replacement Therapy ◽  
Pancreatic Insufficiency ◽  
Skin Irritation ◽  
Exocrine Pancreatic Insufficiency ◽  
Severe Exacerbation ◽  
Enzyme Preparations ◽  
Enzyme Replacement ◽  
Malabsorption Syndromes ◽  
Unpleasant Odor ◽  
Bladder Diseases

The article is an overview of current ideas about indications and features of various enzyme preparations (EP). The following requirements are applied for all EP: nontoxicity, resistance to hydrochloric acid and pepsin, good tolerance by patients, no significant side effects, optimal effect at pH≈6.0, rapid release of enzymatic activity in the small intestine at pH≈6.0, while maintaining this activity no less than 2 hours, high enzyme activity, compliance with the composition stated on the label, high serial homogeneity of the preparation, no unpleasant odor and taste. Considering the variety of pathogenetic mechanisms and nosological units that occur with maldigestion and malabsorption syndromes, the spectrum of indications for EP is rather wide: pancreatic, liver, gall bladder diseases, preparation for instrumental studies, etc. The authors present a modern algorithm (“steps”) of enzyme therapy. A differentiated approach to the choice of EP is developed depending on the pathology that the patient suffers from, EP composition, and features of its action. Attention is drawn to the possible reasons for the lack of effectiveness of replacement therapy, general contraindications to the prescription of EP (acute pancreatitis, severe exacerbation of chronic pancreatitis, hypersensitivity to the drug components) and their individual components (bile acids, nicotinamide, activated charcoal). Complications of enzyme replacement therapy are indicated, namely: pain in the oral cavity; skin irritation in the perianal region; abdominal discomfort; nausea; fibrosing colopathy; allergic reactions; sometimes hyperuricosuria; pancreatin shaping complexes with folic acid, disrupting its absorption.

scholarly journals Mucopolysaccharidosis Type I in Children, a Forgotten Diagnosis Responsible for Undiagnosed Musculoskeletal Complaints: Report of Two Cases

2019 ◽  
Vol 62 (4) ◽  
pp. 161-165
Author(s):  
Soheila Hoseinzadeh Moghadam ◽  
Masood Ghahvechi ◽  
Fatemeh Mozafari ◽  
Fatemeh Sayarifard ◽  
Mahdieh-Sadat Mousavi ◽  
...  
Keyword(s):  
Underlying Mechanism ◽  
Type I ◽  
Musculoskeletal Complaints ◽  
Lysosomal Storage ◽  
Multiple Systems ◽  
Enzyme Replacement ◽  
Presenting Symptoms ◽  
Key Factor ◽  
Delays In Diagnosis ◽  
Clinical Conditions

Mucopolysaccharidoses (MPS) are a subgroup of lysosomal storage disorders. The underlying mechanism of MPS disorders are deficiency in specific enzymes which leads to accumulation of partially degraded glycosaminoglycans (GAGs) in various tissues. A wide variety of manifestations are reported but musculoskeletal complaints are common among them. In milder forms of MPS, musculoskeletal complaints are presenting symptoms. Delays in diagnosis due to unspecific and mild symptoms is common. Misdiagnosis of MPS as juvenile idiopathic arthritis and other inflammatory arthritis disorders is frequent. Early diagnosis and treatment prevents irreversible cellular damages and is a key factor in efficacy of enzyme replacement therapy. In this study we described two MPS patients with musculoskeletal complaints who were not diagnosed for a period of time. Although musculoskeletal manifestation are common in a variety of clinical conditions, their presence at low ages or co-occurrence of other manifestations (such as cardiac, respiratory, neurologic, etc.) in multiple systems should prompt evaluation of patients for MPS and other metabolic disorders. The rheumatologists’ awareness on MPS should be promoted to achieve timely diagnosis and subsequent early treatment.

scholarly journals Clinical course and approaches to the therapy of chronic pancreatitis in patients with comorbid pathology

2017 ◽  
Vol 36 (2) ◽  
pp. 45-48
Author(s):  
Т. А. Ruzhentsova
Keyword(s):  
Quality Of Life ◽  
Chronic Pancreatitis ◽  
Cardiovascular Diseases ◽  
Enzyme Replacement Therapy ◽  
Cardiovascular System ◽  
Replacement Therapy ◽  
Clinical Course ◽  
Enzyme Replacement

The features of pathogenesis, clinical course and diagnostics of chronic pancreatitis combined with diseases of the cardiovascular system are discussed in the article. Results of the author’s own research on the effectiveness of influence of enzyme replacement therapy on the course of pancreatitis and comorbid pathology are presented. Significant positive dynamics of both manifestations of chronic pancreatitis and cardiovascular diseases, laboratory and instrumental examinations, improvement of patients’ quality of life upon the prescription of pancreatin are noted.

scholarly journals Enzyme replacement therapy, life quality and expectancy of patients with chronic pancreatitis and exocrine pancreatic insufficiency

2018 ◽  
Vol 41 (3) ◽  
pp. 10-16
Author(s):  
N. B. Gubergrits ◽  
N. V. Byelyayeva ◽  
А. Y. Klochkov ◽  
G. М. Lukashevich ◽  
P. G. Fomenko ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Pancreatic Insufficiency ◽  
Life Quality ◽  
Exocrine Pancreatic Insufficiency ◽  
Enzyme Preparations ◽  
Enzyme Replacement ◽  
Enteric Coated ◽  
Adequate Dosage

The article reviews the evidence-based studies devoted to the evaluation of the efficacy and safety of enzyme replacement therapy in patients with chronic pancreatitis with exocrine pancreatic insufficiency. Particular attention is paid to the effect of replacement therapy on the life quality and expectancy of patients. It has been proven that the correct prescription of enzyme preparations (minimicrosphere enteric-coated preparation, adequate dosage) improves the quality and prolongs the life of patients.

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