Reviewing The Latest Treatments for Haemophilia

Abstract: Advancements in haemophilia treatment have been significant in the first 20 years of the 21st century. However, the progress started with the fractionation of plasma in 1946. The first concentrates were developed after discovering FVIII in frozen plasma cryoprecipitate and FIX in the supernatant in the early 1960s, leading to initial attempts at replacement therapy. Unfortunately, due to the lack of screening methods for viral pathogens, people with haemophilia (PWH) received contaminated concentrates, leading to infections with the hepatitis A virus, hepatitis C virus, and human immunodeficiency virus. Thankfully, by 1985, viral screening methods and virucidal techniques were developed, making concentrates safe. The introduction of chromatography steps with monoclonal antibodies in the production process led to increasingly pure products. However, the problem of immunogenicity of administered concentrates persists. The development of alloantibodies against FVIII in a significant percentage of PWH is a serious adverse effect of replacement therapy. The next major advancement came with cloning the F8 and F9 genes, which allowed the production of factor concentrates using recombinant DNA technology. The injected FVIII and FIX molecules have a relatively short circulating half-life in the plasma of people with haemophilia A and B, approximately 12 and 18 hours, respectively. Methods such as conjugating the factor molecule with fragment crystallizable of IgG1, albumin, or adding polyethylene glycol have been applied to prolong the plasma half-life and extend the interval between injections, especially for risk. The next frontier in haemophilia therapy is the development of durable and potentially curative treatments, such as gene addition therapy. Experiments in haemophilia B have shown promising long-lasting responses. However, the results of gene therapy for haemophilia A have not been as remarkable, and the durability of the treatment is yet to be demonstrated. The long-term safety, predictability, durability, and efficacy of gene therapy for haemophilia A and B remain open questions. Currently, only healthy adult PWH has been enrolled in gene therapy clinical trials, and further studies are needed before gene therapy can be widely applied to children and those with pre-existing antibodies against the delivery vector.