70
2.8.7 Pegloticase
Gout and inflammatory disease occur due to accumulation of monosodium urate
crystals in joints. Hyperuricaemia is the key player here too. Urate oxidase enzymes
can alleviate hyperurecaemia too. Though rasburicase (urate oxidase) is helpful in
managing TLS, immunogenicity and a short half-life make it impractical for use in
gout. As gout is intolerant to urate-lowering strategies, recombinant mammalian
uricase was developed. Pegloticase is a PEGylated variant of recombinant porcine/
baboon urate oxidase expressed in E. coli (Ea and Richette 2012) and got US Food
and Drug Administration (FDA) approval in 2010 for the treatment of chronic gout.
Pegloticase is available commercially as Krystexxa
®
.
2.8.8 Glucarpidase
Methotrexate (MTX) and other antifolates administered for cancer therapy are normally eliminated through urine. High-dose methotrexate (HDMTX) is taken with
precautions; however, improper elimination can lead to toxicities and renal failure.
Carboxypeptidase enzymes hydrolyse MTX into non-toxic products. Glucarpidase
is a recombinant Pseudomonas carboxypeptidase G2 expressed in E. coli. It readily
cleaves MTX into glutamate and 2, 4- diamino-N10-methyl-pteroic acid and is
excreted by the hepatic system (Sherwood et al. 1985).
2.8.9 Ocriplasmin
Ocriplasmin is the truncated recombinant mutant of plasmin while retaining its
fibrinolytic potential and it is expressed in Pichia pastoris (Nagai et al. 2003).
Vitreomacular adhesion occurs due to partial vitreous detachment characterized by
attachment of a part of the vitreous to the macula. It may form macular holes while
traction occurs. Vitrectomy is the only remedy for this condition. However, vitreous
liquefaction and detachment from the retina can be treated with ocriplasmin for
bypassing surgical protocols. Vitreomacular adhesion happens via proteoglycans
including fibronectin and laminin, which are plasmin receptors. Proteolytic action
of ocriplasmin against fibronectin and laminin helps in vitreomacular detachment.
Thus ocriplasmin aids in release of traction and macular hole closure (Stalmans
et al. 2012). It is commercially available as JETREA
®
.
2.9
Conclusions
Enzymes have great potency in therapeutic applications. Though therapeutic
enzyme development is not a new approach, FDA approval has been received by
only a few enzymes and available for clinical application while some of the therapeutic enzymes are in clinical trials. Success of therapeutic enzyme application has
S.S. Kumar and S. Abdulhameed
2.8.7 Pegloticase
Gout and inflammatory disease occur due to accumulation of monosodium urate
crystals in joints. Hyperuricaemia is the key player here too. Urate oxidase enzymes
can alleviate hyperurecaemia too. Though rasburicase (urate oxidase) is helpful in
managing TLS, immunogenicity and a short half-life make it impractical for use in
gout. As gout is intolerant to urate-lowering strategies, recombinant mammalian
uricase was developed. Pegloticase is a PEGylated variant of recombinant porcine/
baboon urate oxidase expressed in E. coli (Ea and Richette 2012) and got US Food
and Drug Administration (FDA) approval in 2010 for the treatment of chronic gout.
Pegloticase is available commercially as Krystexxa
®
.
2.8.8 Glucarpidase
Methotrexate (MTX) and other antifolates administered for cancer therapy are normally eliminated through urine. High-dose methotrexate (HDMTX) is taken with
precautions; however, improper elimination can lead to toxicities and renal failure.
Carboxypeptidase enzymes hydrolyse MTX into non-toxic products. Glucarpidase
is a recombinant Pseudomonas carboxypeptidase G2 expressed in E. coli. It readily
cleaves MTX into glutamate and 2, 4- diamino-N10-methyl-pteroic acid and is
excreted by the hepatic system (Sherwood et al. 1985).
2.8.9 Ocriplasmin
Ocriplasmin is the truncated recombinant mutant of plasmin while retaining its
fibrinolytic potential and it is expressed in Pichia pastoris (Nagai et al. 2003).
Vitreomacular adhesion occurs due to partial vitreous detachment characterized by
attachment of a part of the vitreous to the macula. It may form macular holes while
traction occurs. Vitrectomy is the only remedy for this condition. However, vitreous
liquefaction and detachment from the retina can be treated with ocriplasmin for
bypassing surgical protocols. Vitreomacular adhesion happens via proteoglycans
including fibronectin and laminin, which are plasmin receptors. Proteolytic action
of ocriplasmin against fibronectin and laminin helps in vitreomacular detachment.
Thus ocriplasmin aids in release of traction and macular hole closure (Stalmans
et al. 2012). It is commercially available as JETREA
®
.
2.9
Conclusions
Enzymes have great potency in therapeutic applications. Though therapeutic
enzyme development is not a new approach, FDA approval has been received by
only a few enzymes and available for clinical application while some of the therapeutic enzymes are in clinical trials. Success of therapeutic enzyme application has
S.S. Kumar and S. Abdulhameed