Novel dual-action fusion proteins combining truncated ADAMTS13 and a nanobody against VWF

Yunpeng Xue, M.Sc.
Synapse Research Institute
Maastricht, the Netherlands

The primary cause of thrombotic thrombocytopenic purpura (TTP) is the impaired degradation of ultra-large von Willebrand factor (VWF) multimers, leading to microvascular thrombosis. Two key therapeutic targets are the restoration of ADAMTS13 activity, which is often neutralized by autoantibodies, and the inhibition of pathological VWF-platelet interactions.

In this presentation, Yunpeng Xue introduces a novel class of dual-action fusion proteins that combine a truncated form of ADAMTS13 with a nanobody targeting the A1 domain of VWF. These fusion proteins were evaluated in multiple functional assays and demonstrated both enhanced cleavage of VWF multimers and effective inhibition of VWF-platelet binding.

These findings highlight dual-action fusion proteins as a promising new therapeutic strategy for the treatment of TTP.