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Clinical Applications of Hyaluronidase

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Therapeutic Enzymes: Function and Clinical Implications

Abstract

Hyaluronidases are enzymes that degrade hyaluronic acid, which constitutes an essential part of the extracellular matrix. Initially discovered in bacteria, hyaluronidases are known to be widely distributed in nature and have been found in many classes including insects, snakes, fish and mammals. In the human, six different hyaluronidases, HYAL1-4, HYAL-P1 and PH-20, have been identified. PH-20 exerts the strongest biologic activity, is found in high concentrations in the testicles and can be localized on the head and the acrosome of human spermatozoa. Today, animal-derived bovine or ovine testicular hyaluronidases as well as synthetic hyaluronidases are clinically applied as adjuncts to increase the bioavailability of drugs, for the therapy of extravasations, or for the management of complications associated with the aesthetic injection of hyaluronic acid-based fillers. Further applications in the fields of surgery, aesthetic medicine, immunology, oncology, and many others can be expected for years to come. Here, we give an overview over the molecular and cellular mode of action of hyaluronidase and the hyaluronic acid metabolism, as well as over current and potential future clinical applications of hyaluronidase.

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Abbreviations

BEL:

Belotero®

BTH:

Bovine testicular hyaluronidase

CHO:

Chinese hamster ovary

CPM:

Cohesive polydensified matrix

DMSO:

Dimethylsulfoxide

ECM:

Extracellular matrix

EMV:

Emervel®

FDA:

Food and Drug Administration

GAG:

Glycosaminoglycan

HA:

Hyaluronan

HAS:

Hyaluronan synthase

HYAL:

Hyaluronidase

Ig:

Immunoglobulin

IGSC:

Subcutaneous immunoglobulins

IU:

International units

JUV:

Juvederm®

kDA:

Kilodalton

l:

Liter

LA:

Local anesthetic

mAb:

Monoclonal antibody

ml:

Milliliter

μm:

Micrometer

OTH:

Ovine testicular hyaluronidase

PEGPH20:

PEGylated recombinant human hyaluronidase

PG:

Proteoglycan

RES:

Restylane®

rHuPH20:

Recombinant human hyaluronidase

S. aureus :

Staphylococcus aureus

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Weber, G.C., Buhren, B.A., Schrumpf, H., Wohlrab, J., Gerber, P.A. (2019). Clinical Applications of Hyaluronidase. In: Labrou, N. (eds) Therapeutic Enzymes: Function and Clinical Implications. Advances in Experimental Medicine and Biology, vol 1148. Springer, Singapore. https://doi.org/10.1007/978-981-13-7709-9_12

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