Collagenase Collagenases are enzymes that break the peptide bonds in collagen. They assist in destroying extracellular structures in the pathogenesis of bacteria such as ''Clostridium''. They are considered a virulence factor, facilitating the spread of ...

''clostridium histolyticum'' is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

produced by the bacterium ''

Clostridium histolyticum ''Hathewaya histolytica'' (formerly ''Clostridium histolyticum'') is a species of bacteria found in feces and the soil. It is a motile, gram-positive, aerotolerant anaerobe. ''H. histolytica'' is pathogenic in many species, including guinea pigs ...

''that dismantles

collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

. It is used as a powder-and-solvent injection kit for the treatment of

Dupuytren's contracture Dupuytren's contracture (also called Dupuytren's disease, Morbus Dupuytren, Viking disease, palmar fibromatosis and Celtic hand) is a condition in which one or more fingers become progressively bent in a flexed position. It is named after Guilla ...

, a condition where the fingers bend towards the palm and cannot be fully straightened, and

Peyronie's disease Peyronie's disease is a connective tissue disorder involving the growth of fibrous plaques in the soft tissue of the penis. Specifically, scar tissue forms in the tunica albuginea, the thick sheath of tissue surrounding the corpora cavernosa, ca ...

, a connective tissue disorder involving the growth of fibrous plaques in the soft tissue of the penis. BioSpecifics Technologies developed the preparation, which is manufactured and marketed by

Endo Pharmaceuticals Endo International plc is an American Irish-domiciled generics and specialty branded pharmaceutical company that generated over 93% of its 2017 sales from the U.S. healthcare system. While Endo's management, operations, and customers are almost ...

as Xiaflex in the US and by Sobi as Xiapex in Europe. Biochemically, it is a mixture of two ''C. histolyticum'' collagenases, ''ColH'' and ''ColG''. A similar ointment preparation called

Santyl Collagenases are enzymes that break the peptide bonds in collagen. They assist in destroying extracellular structures in the pathogenesis of bacteria such as ''Clostridium''. They are considered a virulence factor, facilitating the spread of ...

contains one or many collagenases from the same bacterium, but it is unclear which.

Uses

In February 2010, the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

of the United States approved Xiaflex for the treatment of Dupuytren's contracture. It is the first approved nonsurgical treatment for this condition. In a case of Dupuytren's contracture,

accumulates in the palmar fascia of the hands, so that the fingers cannot be straightened. A similar phenomenon occurs in

, a contracture of the penis. Xiaflex (Collagenase) for Dupuytrens

In February 2011, the European Commission's

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regarding ...

approved the product for the treatment of Dupuytren's contracture in adults with a palpable cord by 'properly trained' doctors. Pfizer was reported to be working with Europe's national medicines regulatory bodies to launch the new treatment, hoping doctors could prescribe the treatment by late 2011. However, the Swedish manufacturer abruptly withdrew distribution of this drug in Europe in March 2020 for commercial reasons. Collagenase is no longer available on the National Health System except as part of a small clinical trial. On November 7, 2012, BioSpecifics announced Auxilium's submission of a License Application to the FDA for Xiaflex for the potential treatment of Peyronie's disease, an excess of inelastic collagen causing penile curvature deformity. The FDA approved Xiaflex for the treatment of Peyronie’s disease in December 2013. Following this, Xiapex gained EU approval for the treatment of Peyronie’s disease in February 2015, making it the first and only biologic therapy indicated for the treatment of Peyronie's disease. Auxilium has also reported additional trials for potential use of Xiaflex are underway for the treatment of

frozen shoulder Adhesive capsulitis, also known as frozen shoulder, is a condition associated with shoulder pain and stiffness. It is a common shoulder ailment that is marked by pain and a loss of range of motion, particularly in external rotation. There is a ...

, cellulite reductions and both human and canine

lipoma A lipoma is a benign tumor made of fat tissue. They are generally soft to the touch, movable, and painless. They usually occur just under the skin, but occasionally may be deeper. Most are less than in size. Common locations include upper back, ...

Side effects

The most common side effects include

lymphadenopathy Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cli ...

(swollen

lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...

s), itching, pain,

oedema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...

, and bleeding (for example in the form of

bruise A bruise, also known as a contusion, is a type of hematoma of tissue, the most common cause being capillaries damaged by trauma, causing localized bleeding that extravasates into the surrounding interstitial tissues. Most bruises occur close ...

s or

ecchymoses A bruise, also known as a contusion, is a type of hematoma of tissue, the most common cause being capillaries damaged by trauma, causing localized bleeding that extravasates into the surrounding interstitial tissues. Most bruises occur close e ...

Allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...

s are seen in less than 1% of patients.

Chemical properties

The substance is a constant mixture of two collagenases (AUX-I and AUX-II) with known

amino acid sequence Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthe ...

s and a length of about 1000 amino acids each. It is prepared by

anaerobic fermentation Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food p ...

from a

strain Strain may refer to: Science and technology * Strain (biology), variants of plants, viruses or bacteria; or an inbred animal used for experimental purposes * Strain (chemistry), a chemical stress of a molecule * Strain (injury), an injury to a mu ...

of ''C. histolyticum'' that has been known since 1950.

Pharmacology

The enzymes do not reach the bloodstream in significant amounts and are presumed to largely stay at the point of injection until they are broken down by

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...

s. The two collagenases act

synergistic Synergy is an interaction or cooperation giving rise to a whole that is greater than the simple sum of its parts. The term ''synergy'' comes from the Attic Greek word συνεργία ' from ', , meaning "working together". History In Christi ...

ally by cleaving

tropocollagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

(the 'collagen molecule') at different points. AUX-I attacks the C- and

N-termini The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

, AUX-II cleaves amino acid bonds within the molecule. Small collagen fragments are broken down by both enzymes.

Interactions

No interaction studies have been conducted because the drug does not reach the bloodstream and the liver. It is theorised that drugs interfering with

matrix metalloproteinase Matrix metalloproteinases (MMPs), also known as matrix metallopeptidases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs b ...

s, such as

tetracyclines Tetracyclines are a group of broad-spectrum antibiotic compounds that have a common basic structure and are either isolated directly from several species of ''Streptomyces'' bacteria or produced semi-synthetically from those isolated compounds. T ...

anthracyclines Anthracyclines are a class of drugs used in cancer chemotherapy that are extracted from ''Streptomyces'' bacterium. These compounds are used to treat many cancers, including leukemias, lymphomas, breast, stomach, uterine, ovarian, bladder cance ...

quinolones Quinolone may refer to: * 2-Quinolone * 4-Quinolone 4-Quinolone is an organic compound derived from quinoline. It and 2-quinolone are the two most important parent (meaning simplified) quinolones. 4-Quinolone exists in equilibrium with a mino ...

and

anthraquinone Anthraquinone, also called anthracenedione or dioxoanthracene, is an aromatic organic compound with formula . Isomers include various quinone derivatives. The term anthraquinone however refers to the isomer, 9,10-anthraquinone (IUPAC: 9,10-dioxo ...

derivatives, could reduce the efficacy of the collagenases, but no clinical evidence for such an interaction has been observed.

References

External links

* {{Portal bar, Biology, Medicine, border=no Drugs acting on the musculoskeletal system EC 3.4.24 Orphan drugs