Skip to main content

Therapeutic Enzymes

  • Chapter
  • First Online:
Bioresources and Bioprocess in Biotechnology

Abstract

Enzymes as therapeutics hold a few advantages over non-enzymatic drugs with their amazing specificity towards targets as well as multiple substrate conversion. Development of enzyme therapeutics against rare diseases such as lysosomal storage disorders and severe combined immunodeficiency undoubtedly raised the hope of patients and improved their quality of life. Development of enzyme therapeutics against cardiovascular diseases witnessed a tremendous explosion in the past four to five decades and resulted in the development of the first approved genetically engineered drug against cardiovascular diseases (Activase®). Since then many recombinant cardiovascular drugs have been approved for clinical application. Often immunogenicity associated with enzyme drugs and the cost of production are major setbacks for their development. Despite their advantages only a few enzymes were approved by the Food and Drug Administration (FDA).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ali MR, Salim Hossain M, Islam MA, Saiful Islam Arman M, Sarwar Raju G, Dasgupta P, Noshin TF (2014) Aspect of thrombolytic therapy: a review. Sci World J 2014:586510

    Google Scholar 

  • Baker SS (2008) Delayed release pancrelipase for the treatment of pancreatic exocrine insufficiency associated with cystic fibrosis. Ther Clin Risk Manag 4:1079–1084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bayol A, Capdevielle J, Malazzi P, Buzy A, Claude Bonnet M, Colloch N, Mornon JP, Loyaux D, Ferrara P (2002) Modification of a reactive cysteine explains differences between rasburicase and Uricozyme, a natural Aspergillus flavus uricase. Biotechnol Appl Biochem 36:21–31

    Article  CAS  PubMed  Google Scholar 

  • Beard J (1906) The action of trypsin upon the living cells of jensen’s mouse-tumour. Br Med J 1:140–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bernik MB (1973) Increased plasminogen activator (urokinase) in tissue culture after fibrin deposition. J Clin Invest 52:823–834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bhagat S, Agarwal M, Roy V (2013) Serratiopeptidase: a systematic review of the existing evidence. Int J Surg 11:209–217

    Article  PubMed  Google Scholar 

  • Bijvoet AG, Van Hirtum H, Kroos MA, Van de Kamp EH, Schoneveld O, Visser P, Brakenhoff JP, Weggeman M, van Corven EJ, Van der Ploeg AT, Reuser AJ (1999) Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II. Hum Mol Genet 8:2145–2153

    Article  CAS  PubMed  Google Scholar 

  • Collen D, Van de Werf F (1993) Coronary thrombolysis with recombinant staphylokinase in patients with evolving myocardial infarction. Circulation 87:1850–1853

    Article  CAS  PubMed  Google Scholar 

  • Coppola A, Di Capua M, Di Minno MND, Di Palo M, Marrone E, Ieranò P, Arturo C, Tufano A, Cerbone AM (2010) Treatment of hemophilia: a review of current advances and ongoing issues. Journal of Blood Medicine 1:183–195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Duve C (1966) The significance of lysosomes in pathology and medicine. Proceedings of the Institute of Medicine of Chic 26:73–76

    Google Scholar 

  • Ea HK, Richette HK (2012) Critical appraisal of the role of pegloticase in the management of gout. Open Access Rheumatology: Research and Reviews 4:63–70

    Article  CAS  Google Scholar 

  • Elstein D (2011) Recent advances in treatment approaches to gaucher disease. Curr Pharm Biotechnol 12:854–860

    Article  CAS  PubMed  Google Scholar 

  • Ensor CM, Holtsberg FW, Bomalaski JS, Clark MA (2002) Pegylated arginine deiminase (ADI-SS PEG 20,000 mw) inhibits human melanomas and hepatocellular carcinomas in vitro and in vivo. Cancer Res 62:5443–5450

    CAS  PubMed  Google Scholar 

  • Falabella AF (2006) Debridement and wound bed preparation. Dermatol Ther 19:317–325

    Article  PubMed  Google Scholar 

  • Flohe L (1988) Superoxide dismutase for therapeutic use: clinical experience, dead ends and hopes. Mol Cell Biochem 84:123–131

    Article  CAS  PubMed  Google Scholar 

  • Gass J, Ehren J, Strohmeier G, Isaacs I, Khosla C (2005) Fermentation, purification, formulation, and pharmacological evaluation of a prolyl endopeptidase from Myxococcus xanthus: implications for celiac sprue therapy. Biotechnol Bioeng 92:674–684

    Article  CAS  PubMed  Google Scholar 

  • Goa KL, Henwood JM, Stolz JF, Langley MS, Clissold SP (1990) Intravenous streptokinase. A reappraisal of its therapeutic use in acute myocardial infarction. Drugs 39:693–719

    Article  CAS  PubMed  Google Scholar 

  • Hoffman M, Dargaud Y (2012) Mechanisms and monitoring of bypassing agent therapy. J Thromb Haemost 10:1478–1485

    Article  CAS  PubMed  Google Scholar 

  • Honig SC (2014) Intralesional collagenase in the treatment of Peyronie’s disease. Ther Adv Urol 6:47–53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones AP, Wallis C (2010) Dornase alfa for cystic fibrosis. Cochrane Database Syst Rev 3:1–66

    Google Scholar 

  • Kim JY, Gum SN, Paik JK, Lim HH, Kim KC, Ogasawara K, Inoue K, Park S, Jang Y, Lee JH (2008) Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertens Res 31:1583–1588

    Article  CAS  PubMed  Google Scholar 

  • Kim RH, Coates JM, Bowles TL, McNerney GP, Sutcliffe J, Jung JU, Gandour-Edwards R, Chuang FYS, Bold RJ, Kung HJ (2009) Arginine deiminase as a novel therapy for prostate cancer induces autophagy and caspase-independent apoptosis. Cancer Res 69:700–708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kurosawa Y, Nirengi S, Homma T, Esaki K, Ohta M, Clark JF, Hamaoka T (2015) A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep 5:1–7

    Article  Google Scholar 

  • Kurtzberg J, Asselin B, Bernstein M, Buchanan GR, Pollock BH, Camitta BM (2011) Polyethylene glycol-conjugated L-asparaginase versus native L-asparaginase in combination with standard agents for children with acute lymphoblastic leukemia in second bone marrow relapse: a Children’s oncology group study (Pog 8866). J Pediatr Hematol Oncol 33:610–616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lampe BJ, English JC (2016) Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto. Food Chem Toxicol 88:87–99

    Article  CAS  PubMed  Google Scholar 

  • Longo N, Harding CO, Burton BK, Grange DK, Vockley J, Wasserstein M, Rice GM, Dorenbaum A, Neuenburg JK, Musson DG, Gu Z, Sile S (2014) Single-dose, subcutaneous recombinant phenylalanine ammonia lyase conjugated with polyethylene glycol in adult patients with phenylketonuria: an open-label, multicentre, phase 1 dose-escalation trial. Lancet 384:37–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McCallon SK, Weir D, Lantis JC (2014) Optimizing wound bed preparation with collagenase enzymatic debridement. The Journal of the American College of Clinical Wound Specialists 6:14–23

    Article  PubMed  Google Scholar 

  • Mehta A, Beck M, Eyskens F, Feliciani C, Kantola I, Ramaswami U, Rolfs A, Rivera A, Waldek S, Germain DP (2010) Fabry disease: a review of current management strategies. Q J Med 103:641–659

    Article  CAS  Google Scholar 

  • Moriya N, Nakata M, Nakamura M, Takaoka M, Iwasa S, Kato K, Kakinuma A (1994) Intestinal absorption of serrapeptase (TSP) in rats. Biotechnol Appl Biochem 20:101–108

    CAS  PubMed  Google Scholar 

  • Nagai N, Demarsin E, Van Hoef B, Wouters S, Cingolani D, Laroche Y, Collen D (2003) Recombinant human microplasmin: production and potential therapeutic properties. J Thromb Haemost 1:307–313

    Article  CAS  PubMed  Google Scholar 

  • Noh H, Lee JI (2014) Current and potential therapeutic strategies for mucopolysaccharidoses. Journal of Clinical Pharmacology and Therapeutics 39:215–224

    Article  CAS  Google Scholar 

  • Pan R, Zhang ZJ, He RQ, Pan R, Zhang ZJ, He RQ (2010) Earthworm Protease. Applied and Environmental Soil Science 2010:e294258

    Article  Google Scholar 

  • Pennica D, Holmes WE, Kohr WJ, Harkins RN, Vehar GA, Ward CA, Bennett WF, Yelverton E, Seeburg PH, Heyneker HL, Goeddel DV, Collen D (1983) Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli. Nature 301:214–221

    Article  CAS  PubMed  Google Scholar 

  • Peters RT, Low SC, Kamphaus GD, Dumont JA, Amari JV, Lu Q, Zarbis-Papastoitsis G, Reidy TJ, Merricks EP, Nichols TC, Bitonti AJ (2010) Prolonged activity of factor IX as a monomeric fc fusion protein. Blood 115:2057–2064

    Article  CAS  PubMed  Google Scholar 

  • Peters RT, Toby G, Lu Q, Liu T, Kulman JD, Low SC, Bitonti AJ, Pierce GF (2013) Biochemical and functional characterization of a recombinant monomeric factor VIII-fc fusion protein. J Thromb Haemost 11:132–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shan L, Marti T, Sollid LM, Gray GM, Khosla C (2004) Comparative biochemical analysis of three bacterial prolyl endopeptidases: implications for coeliac sprue. Biochem J 383:311–318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shapira E, Giladi A, Neuman Z (1973) Use of water-insoluble papain (WIP) for debridement of burn eschar and necrotic tissue. Preliminary report. Plast Reconstr Surg 52:279–281

    Article  CAS  PubMed  Google Scholar 

  • Sherwood RF, Melton RG, Alwan SM, Hughes P (1985) Purification and properties of carboxypeptidase G2 from Pseudomonas sp. strain RS-16. Use of a novel triazine dye affinity method. Eur J Biochem 148:447–453

    Article  CAS  PubMed  Google Scholar 

  • Smalling RW (1996) Molecular biology of plasminogen activators: what are the clinical implications of drug design? Am J Cardiol 78:2–7

    Article  CAS  PubMed  Google Scholar 

  • Smith RA, Dupe RJ, English PD, Green J (1981) Fibrinolysis with acyl-enzymes: a new approach to thrombolytic therapy. Nature 290:505–508

    Article  CAS  PubMed  Google Scholar 

  • Stalmans P, Benz MS, Gandorfer A, Kampik A, Girach A, Pakola S, Haller JA (2012) Enzymatic Vitreolysis with ocriplasmin for vitreomacular traction and macular holes. N Engl J Med 367:606–615

    Article  CAS  PubMed  Google Scholar 

  • Sumi H, Hamada H, Tsushima H, Mihara H, Muraki H (1987) A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese natto; a typical and popular soybean food in the Japanese diet. Experientia 43:1110–1111

    Article  CAS  PubMed  Google Scholar 

  • Van Hove JL, Yang HW, Wu JY, Brady RO, Chen YT (1996) High-level production of recombinant human lysosomal acid alpha-glucosidase in Chinese hamster ovary cells which targets to heart muscle and corrects glycogen accumulation in fibroblasts from patients with pompe disease. Proceedings of the National Academy Sciences of United States of America 93:65–70

    Article  Google Scholar 

  • White MJV, Glenn M, Gomer RH (2013) Trypsin potentiates human fibrocyte differentiation. PLoS One 8:e70795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zamarron C, Lijnen HR, Van Hoef B, Collen D (1984) Biological and thrombolytic properties of proenzyme and active forms of human urokinase--I. Fibrinolytic and fibrinogenolytic properties in human plasma in vitro of urokinases obtained from human urine or by recombinant DNA technology. Thromb Haemost 52:19–23

    CAS  PubMed  Google Scholar 

  • Zimran A, Brill-Almon E, Chertkoff R, Petakov M, Blanco-Favela F, Muñoz ET, Solorio-Meza SE, Amato D, Duran G, Giona F, Heitner R, Rosenbaum H, Giraldo P, Mehta A, Park G, Phillips M, Elstein D, Altarescu G, Szleifer M, Hashmueli S, Aviezer D (2011) Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for gaucher disease. Blood 118:5767–5773

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sabu Abdulhameed .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Nature Singapore Pte Ltd.

About this chapter

Cite this chapter

Kumar, S.S., Abdulhameed, S. (2017). Therapeutic Enzymes. In: Sugathan, S., Pradeep, N., Abdulhameed, S. (eds) Bioresources and Bioprocess in Biotechnology. Springer, Singapore. https://doi.org/10.1007/978-981-10-4284-3_2

Download citation

Publish with us

Policies and ethics