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(Title) Proteases (medical and related uses)


 * See also article: Protease, for structure and properties of proteolytic enzymes

Proteases (also sometimes referred to as proteolytic enzymes or peptidases) are in use, or have been proposed or tried, for a number of purposes related to medicine or surgery. Some preparations involving protease have undergone successful clinical trials and have regulatory authorization; and some further ones have shown apparently useful effects in experimental medical studies. Proteases have also been used by proponents of alternative therapies, or identified in materials of traditional or folk medicine.

Some of these uses rely directly on the proteolytic activity: others rely on observations of anti-inflammatory activity. For at least one significant use, the mechanism of action is unclear.

Treatment of blood clots in ischemic stroke
Tissue plasminogen activator (TPA) is a serine protease occurring in animals including humans. Human-identical TPA (produced industrially by genetically recombinant microorganisms) has an established medical use in the treatment of ischemic stroke: by its proteolytic activity it enables the action of another enzyme (plasmin), which breaks down the protein (fibrin) of blood clots.

Wound debridement
Debridement involves the removal of dead or damaged tissue from wounds in order to assist healing. Much of the debris to be removed is proteinaceous, and proteolytic enzymes have been applied to this purpose.

Papain is a protease obtained from the latex of the fruit of the papaya tree. It has been used (without regulation) for wound debridement for many years, but in the USA in 2008 it was brought under regulation by the FDA and removed from sale for this purpose, following reports of adverse effects. On the other hand, recent research has been exploring new ways of administering papain for wound debridement.

Papain as well as other proteases, including bromelain, collagenase, trypsin and thermolysin, have also been tried or used according to other reports on the use of proteases for debridement of wounds and burns without damaging healthy tissue.

Maggot therapy for wound debridement is a traditional therapy which was in recent years approved by the FDA. It has been identified that the maggots produce proteolytic enzymes which take part in the debridement process.

Applications of proteases auxiliary to antibiotic therapy
Some pathogenic bacteria produce biofilms or exudates containing protein, which in some degree help the bacteria adhere to host tissue, or in some degree physically shield the bacteria or hinder the penetration of substances such as antibiotics administered with the intent that they contact the bacteria. Accordingly, proteolytic enzymes have been tried in conjunction with antibiotics. Thus, it has been reported that Serratia E-15 protease (also known as serratiopeptidase) was effective for eradicating infection caused by biofilm-forming bacteria in an experimental animal model (which involved carrying out experimental limb surgery on rats, at the same time experimentally introducing Staphylococcus infection). The authors considered that "The antibiofilm property of the enzyme may enhance antibiotic efficacy in the treatment of staphylococcal infections."

The same enzyme, when used concomitantly with an antibiotic, was also reported to increase antibiotic concentration at a target site.

Applications of protease based on anti-inflammatory activity
Bromelain is a protease usually obtained from pineapple stem tissue, which has been medically used for its anti-inflammatory effects (see Bromelain - medical uses and references cited in that article).

Serratia E-15 protease (also known as serratiopeptidase or 'serrapeptidase') is another protease that has been proposed as an anti-inflammatory agent. Anti-inflammatory effects of this protease have been reported again more recently, and the material has come into some use in alternative or complementary medicine. On the other hand, it does not appear that there are positive clinical trial results for this material of a kind that would be needed to gain regulatory approval for controlled pharmaceutical uses.

Medical applications of protease where the mechanism is unclear
Drotrecogin alfa (also known as Xigris (TM)) is a serine protease of human origin, designated protein C, produced in recombinant form and licensed for intensive-care treatment of severe sepsis. It appears unclear whether its effects arise by its proteolytic activity, or from anti-inflammatory effects, or other mechanism.