Does PEGylated DI have the potential to be an effective therapeutic for Antiphospholipid Syndrome?

Abstract

Antiphospholipid Syndrome (APS) has 0.3-1% population prevalence and characterised by clinical phenotypes (thrombotic and obstetric) and the presence of anti-phospholipid antibodies (aPL). APS is the leading cause of strokes in patients 95% throughout. PEGylation was undertaken to extend half life and reduce immunogenicity. I achieved conjugation yields of ~ 50% mono-PEGylated species (molar yield) with minimal waste Di-PEGylated product. Expression tag was removed and endotoxin removed successfully and prepared for final testing. Activity testing included a novel thrombotic functional test, two competition ELISAs (IgG (n=6) & IgA (n=4) ) and a mouse model. All assays showed a high level of retained activity for the protein. Using a novel functional, thrombotic test (n=4), results suggested a gain of function for WT PEGylated species but not PEGylated mutant DI species. In the IgG ELISAs on average >80% activity was retained with similar seen in the IgA assays. Together, these results suggest that PEGylated DI harbours the potential to be the first specific, targeted therapeutic in APS