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The ability of serum from alpha 1-antitrypsin-deficient patients to inhibit PRT-201, a recombinant human type I pancreatic elastase.

Abstract
PRT-201 is a recombinant human pancreatic elastase under development as a treatment for blood vessels to promote hemodialysis access patency. Proteases such as elastase are normally inactivated by antiproteases such as alpha 1-antitrypsin. It is unknown if serum from patients with alpha 1-antitrypsin deficiency will inhibit PRT-201 elastase activity. An assay for PRT-201 elastase activity in the presence of serum was developed and validated. PRT-201 elastase activity inhibition curves were developed using serum and also using purified alpha 1-antitrypsin and alpha 2-macroglobulin. Serum from 15 patients with documented alpha 1-antitrypsin deficiency, some of whom were receiving alpha 1-antitrypsin augmentation therapy, and four normal volunteers was analyzed. Serum from normal volunteers and patients with alpha 1-antitrypsin deficiency completely inactivated PRT-201 elastase activity in vitro. In the alpha 1-antitrypsin-deficient patients, the volume of serum necessary to inhibit elastase activity was related to the serum concentration of alpha 1-antitrypsin and augmentation therapy. Purified alpha 1-antitrypsin and alpha 2-macroglobulin were each alone capable of completely inhibiting PRT-201 elastase activity. It is unlikely that the use of PRT-201 will be associated with negative outcomes in patients with alpha 1-antitrypsin deficiency.
AuthorsAmir A Qamar, Steven K Burke, Jason D Lafleur, Bee C Ding, Kimberly S Bland, Marco D Wong, Pamela N Gustafson, Andrew T Blair, F Nicholas Franano
JournalBiotechnology and applied biochemistry (Biotechnol Appl Biochem) 2012 Jan-Feb Vol. 59 Issue 1 Pg. 22-8 ISSN: 1470-8744 [Electronic] United States
PMID22332741 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.
Chemical References
  • Recombinant Proteins
  • Pancreatic Elastase
Topics
  • Adult
  • Aged
  • Diabetes Mellitus, Type 1 (enzymology)
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Elastase (antagonists & inhibitors, metabolism)
  • Recombinant Proteins (antagonists & inhibitors, metabolism)
  • Serum
  • alpha 1-Antitrypsin Deficiency (blood, metabolism)

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