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Title: Toxicology studies with recombinant staphylokinase and with SY 161-P5, a polyethylene glycol-derivatized cysteine-substitution mutant
Authors: Moons, Lieve
Vanlinthout, Ingrid
Roelants, Ivo
Moreadith, R
Collen, Desire
Rapold, HJ # ×
Issue Date: Jun-2001
Publisher: Taylor & Francis
Series Title: Toxicologic pathology vol:29 issue:3 pages:285-291
Abstract: SY 161-P5, a polyethylene glycol derivatized (PEGylated) mutant of the recombinant Staphylokinase (rSak) variant SakSTAR, exhibiting reduced antigenicity is in clinical development for treatment of acute myocardial infarction as a single bolus injection. A series of safety studies were performed in vivo as a routine toxicology program with SY 161-P5 (PEG-rSakSTAR) and with the recombinant Staphylokinase variant Sak42D (rSak42D). For both compounds, intravenous single bolus injections of up to 100-fold therapeutic equivalent, as well as repeated injections during 7 to 28 days revealed no significant pathological findings in mice, rats or hamsters. However, New Zealand white rabbits developed clinically silent, multifocal myocarditis following single or repeat doses of SY 161-P5 or of Sak42D. These findings were dose-independent and reversible. A similar species-specific cardiotoxic effect has previously been described for other proteolytic proteins, including the approved drugs Streptokinase and Acetylated Plasminogen Streptokinase Complex (APSAC). The large experience with these drugs, as well as the clinical data accumulated both with PEGylated and non-PEGylated rSak variants to date, do not indicate cardiotoxic hazards associated with the use of these drugs in humans.
ISSN: 0192-6233
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Vesalius Research Centre (-)
Intellectual Property
Animal Physiology and Neurobiology Section - miscellaneous
× corresponding author
# (joint) last author

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