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Honorable Mention Excerpts

Lina Zein

Hathaway Brown School
Shaker Heights, OH
Teacher: Sheri Homany

 

Gene therapy for Hemophilia B

Bleeding conditions that were likely to be hemophilia were described in writings dating as far back as the 2nd Century CE (Franchini & Mannucci, 2014). However, it wasn’t until more recent times that this condition left a mark on modern history. Starting in the second half of the 19th century, and spanning over one-hundred years, several males of royal families in Europe died due to excessive blood loss. They were all descendants of Queen Victoria, including members of the royal families of England, Prussia, Spain, and Russia. Recent DNA analysis (Rogaev EI, 2009) showed that they were afflicted by hemophilia B, a disease affecting blood coagulation…

…Hemophilia B is a rare disorder, occurring in approximately 1 in 30,000 male births (Livnat, et al. 2017). It results from deficient production of clotting factor IX. The lack of normal factor IX disrupts the sequence of reactions needed for blood to clot. This results in excessive bleeding after injuries, even if the injury is minor. Severe bleeding can lead to death or the damage of organs, including the brain, joints, and internal organs (Franchini & Mannucci, 2012)…

…The genetic defect causing hemophilia B is located in the F9 gene of the X-chromosome, at location Xq27.1. It is a recessive X-linked disease, which explains why those affected by the disease are almost always male (NCBI Gene Database, 2017)…

…Ten patients with severe hemophilia B received a one-time intravenous injection of an AAV vector expressing human factor IX gene. The AAV used was engineered to target liver cells, the main site where factor IX is synthesized. The patients were followed for at least 6 months, and some were followed for years. Lasting levels of factor IX between 1 to 8% of normal were seen in all participants (Nathwani et al, 2011; Nathwani et al, 2014). While a low percentage, these results are important because any significant increase in factor IX levels can improve blood clotting (Kumar SRP et al, 2016; Nienhuis AW, 2013). Seven patients were able to stop their regular factor IX infusions, and the other three were able to decrease the frequency of treatments. …