A tolerogenic form of factor VIII (FVIII) is useful as an immunotherapy strategy to prevent inhibitor development in patients with hemophilia A, according to a study published in the Journal of Thrombosis and Haemostasis. 

Recombinant FVIII is the first-line treatment for patients with hemophilia A. However, the development of inhibitors is a serious complication because it limits the treatment options for patients. A research team from the University of Buffalo decided to investigate the merits of a tolerogenic form of FVIII, which was created by associating FVIII with lysophosphatidylserine (Lyso-PS) nanoparticles. 

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This study was conducted on genetically modified hemophilic mice with a targeted deletion in exon 16 of the FVIII gene. The mice models were injected intravenously with the tolerogenic form of FVIII under investigation. Other mice models were given the same medication orally.

The mice models were then challenged weekly with free FVIII and had their serum samples checked to see if inhibitor development occurred. The researchers also performed a pharmacokinetic study following a single intravenous administration of FVIII in the presence and absence of Lyso-PS nanoparticles in order to investigate whether they influenced the plasma survival of FVIII. 

The results of this study demonstrated that the tolerogenic form of FVIII under investigation, FVIII associated with Lyso-PS nanoparticles, significantly reduced the development of inhibitors in genetically modified hemophilic mice models. In addition, plasma survival of FVIII was observed to have increased. This was true in both the IV and the oral administration of the drug, demonstrating that the therapeutic effect of this drug could be achieved through different routes of administration. 

This study showed that immunogenicity against FVIII can be addressed in patients with hemophilia A receiving recombinant FVIII treatment. The researchers concluded, “Our findings also open avenues for an attractive and promising delivery platform to therapeutically deliver FVIII concentrates while simultaneously preventing the risk of inhibitor development.” 


Nguyen NH, Dingman RK, Balu‐Iyer SV. Tolerogenic form of Factor VIII to prevent inhibitor development in the treatment of hemophilia A. J Thromb Haemost. 2021;00:1-7. doi:10.1111/jth.15497