A DNA aptamer to the
von Willebrand factor (VWF) A1 domain, TAGX-0004, inhibits the binding of VWF to platelets.
Nucleic acid aptamers are
single-stranded DNA or
RNA molecule forming three-dimensional structures that are capable of specifically binding to
proteins and are expected to contribute to
alternative medicine.
ARC1779, an aptamer targeting the VWF A1 domain, had been evaluated in a phase II clinical trial of patients with
acquired thrombotic thrombocytopenic purpura (aTTP); however, its development was terminated.
Caplacizumab, an anti-VWF A1 domain nanobody, is now increasingly employed as first-line
therapy for the treatment of aTTP in Western countries. However, there have been reports regarding adverse
bleeding events and the high cost of the treatment. In this study, the inhibitory effects of TAGX-0004 were compared with those of
ARC1779 and
caplacizumab on in vitro platelet aggregation and
thrombus formation. TAGX-0004 had an excellent high affinity to the VWF A1 domain and superior efficacy, such as its potent inhibitory activity in in vitro platelet aggregation and
thrombus formation. Therefore, it can potentially overcome the problems associated with
caplacizumab and can be developed as a promising
drug not only for aTTP treatment but also for the treatment of the various VWF-mediated thrombotic disorders.