Proteases (medical and related uses)
Encyclopedia
Proteases 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.
(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.
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 U.S. Food and Drug Administration 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.
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.
is a protease usually obtained from pineapple stem tissue, which has been medically used for its anti-inflammatory effects (see Bromelain - medical uses).
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.
(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.
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 activatorTissue plasminogen activator
Tissue plasminogen activator is a protein involved in the breakdown of blood clots. It is a serine protease found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown...
(TPA) is a serine protease
Serine protease
Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...
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
DebridementDebridement
Debridement is the medical removal of a patient's dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue...
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
Papain
Papain, also known as papaya proteinase I, is a cysteine protease enzyme present in papaya and mountain papaya .-Papain family:...
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 U.S. Food and Drug Administration 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
Maggot therapy
Maggot therapy is a type of biotherapy involving the intentional introduction of live, disinfected maggots into the non-healing skin and soft tissue wound of a human or animal for the purpose of cleaning out the...
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
BromelainBromelain
Bromelain is a pineapple extract thought to be effective for reducing swelling , especially of the nose and sinuses, after surgery or injury. It may also be used for a variety of other effects that remain scientifically unconfirmed and not authorized by regulatory authorities like the Food and Drug...
is a protease usually obtained from pineapple stem tissue, which has been medically used for its anti-inflammatory effects (see Bromelain - medical uses).
Serratia E-15 protease (also known as serratiopeptidase
Serratiopeptidase
Serratiopeptidase is a proteolytic enzyme produced by enterobacterium Serratia sp. E-15. This microorganism was originally isolated in the late 1960s from silkworm Bombyx mori L...
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 alfaDrotrecogin alfa
Drotrecogin alfa is a recombinant form of human activated protein C that has anti-thrombotic, anti-inflammatory, and profibrinolytic properties. Drotrecogin alpha belongs to the class of serine proteases. Drotrecogin alfa has not been found to improve outcomes in people with severe sepsis...
(also known as Xigris (TM)) is a serine protease
Serine protease
Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...
of human origin, designated protein C
Protein C
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is a zymogenic protein, the activated form of which plays an important role in regulating blood clotting, inflammation, cell death and maintaining the permeability of blood vessel walls in humans and other animals...
, 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.