Honorable Mention Excerpts

Alleanna Marquez

Whitestation High School
Memphis, TN
Teacher: Chikezie Madu


Gene Therapy for Hemophilia

Inherited in an X-linked recessive manner, hemophilia is a disorder typically found in males that affects coagulation [1]. Mutations in the factors VIII (FVIII) and IX (FIX) genes, which are responsible for coagulation, lead to hemophilia A and hemophilia B, respectively; however, the signs and symptoms of the two are nearly indistinguishable [1,2]. Both types of hemophilia have mild, moderate, and severe forms with each form being defined by the factor plasma levels in affected individuals [2,3]. Symptoms of the more severe forms of hemophilia include frequent and spontaneous bleeding as well as bleeding into joints; on the other hand, symptoms of milder forms are subtler, usually only being diagnosed after an affected individual undergoes a surgery or a severe injury [4,5].

Currently, the primary method of treating hemophilia is through protein substitution therapy (PST). In PST, plasma-derived or recombinant replacement clotting factors are delivered into hemophiliacs intravenously typically three times per week, improving their quality of life and increasing their life expectancy [3,4]…

These challenges to hemophilia treatment have made gene therapy an attractive alternative to PST and bypassing agents. Since gene therapy will be able to help generate the necessary clotting factor by transferring either FIX or FVIII genes into target cells, it will hopefully only require a single injection rather than the multiple injections required in PST [3]. Furthermore, by correcting the defective genes in the right cells, enough expression of the clotting factors can be induced to lessen the severity of the disease to a mild phenotype [3,8].

Gene therapy for hemophilia is based on both viral and non-viral approaches. As of now, there are two recombinant viral vectors that demonstrate the most success: adeno-associated virus (AAV) and lentiviral vectors (LV)…

…Despite challenges to gene therapy, one of the most successful clinical trials for gene therapy involved six males, four of which were able to stop frequent prophylactic infusions, and episodes of spontaneous bleeding nearly ceased. Additionally, all experienced and maintained an increase in FIX expression for at least two years [2,10-12]. Clinical trials such as this have increased optimism in establishing a cure through gene therapy for hemophilia….