Research Studies

Objective:

The present study has been conducted to explore the biodistribution of rIX-FP, a recombinant fusion protein linking the human coagulation factor IX to human albumin (CSL Behring GmbH), which is currently being investigated in clinical phase II/III trials (PROLONG- 9FP) for prophylaxis and on-demand treatment of bleeding in hemophilia B patients.

Methods:

Therefore, [3H]-rIX-FP, [3H]-rFIX, or [3H]-albumin were administered intravenously to male rats at a single radioactive dose of 320-420 μCi/kg. Using whole-body autoradiography, tissue radioactivity was determined up to 240 and 24 h following [3H]-rIX-FP and [3H]-albumin, and [3H]-rFIX administration, respectively. In addition to full body sections, the hind limbs were analyzed separately and plasma, urine, and feces were collected to calculate excretion balance and assess physiological elimination pathways.

Summary:

Overall, the tissue distribution of [3H]-rIX-FP and [3H]-rFIX was comparable; both penetrated predominantly into well-perfused tissues, were rapidly present in synovial and mineralized regions of knee joint sections, and seemed to mostly localize to the zone of calcified cartilage within the growth plate regions of long bones, with the longest retention time observed in the bone marrow and endosteum of long bones. Intriguingly, [3H]-rIX-FP signal was detectable over 72 h, whereas comparable [3H]-rFIX signal could only be detected until 24 h post-dosing. Elimination occurred primarily via the urinary route. For [3H]-rIX-FP, after 240 h, 73% of radioactivity was recovered in urine, ≤5% of radioactivity was eliminated in feces, and approximately 20% of radioactivity was present in tissues.

Conclusions:

The study shows that rIX-FP exhibits equal biodistribution compared to other marketed recombinant FIX products, but clearly distinguishes itself from rFIX (BeneFIX®) by its extended plasma half-life, allowing a reduction in dosing frequency leading to increased therapeutic convenience and compliance.

This research project will examine fall history and fall risk in patients with hemophilia. Multiple risk factors for falls identified in the general population are prevalent in the hemophilia population. Existing data suggest that fall rates may be higher and that fall risk may begin at an earlier age in patients with hemophilia. Identification of fall risk enables early intervention, thereby preventing injury and fear of physical activity, both of which have been associated with falling and may carry an increased risk in patients with bleeding disorders.

Dr. Zia earned a MBBS degree from King Edward Medical College, Pakistan. Following an internship in pediatrics at the Children's Hospital, University of Oklahoma Health Sciences Center, she completed her second and third years of pediatric residency at the Children's Hospital of Michigan, Wayne State University in Detroit. Since becoming a hematology/oncology fellow in 2009, Dr. Zia presented at the American Society of Hematology and has had five abstracts accepted for presentation at other major hematology meetings. Dr. Zia will continue her specialized training in pediatric hemostasis-thrombosis under the directorship of Dr. Jeanne Lusher. The NHF-Baxter Clinical Fellowship award will foster Dr. Zia's development as a clinical scientist, allowing her to study clinical research design, statistical analysis as well as pursue research concerning the thrombogenicity of hormonal supplementation in adolescent girls under the mentorship of Drs. Madhvi Rajpurkar and Michael Callaghan, a previous NHF/Baxter clinical fellowship recipient.

Dr. Smith's research focuses on better understanding the development of factor VIII inhibitors. Specifically, she will focus on the effects of chemical signals, or cytokines, secreted by helper T cells on the development of inhibitor antibodies. She hypothesizes that certain cells, called Th17 cells, play an important role in the development of these antibodies by stimulating inflammation and driving the immune response toward inhibitor production. Dr. Smith received a BS from the University of Delaware before earning her Ph.D. from Montana State University. Prior to her appointment as an Assistant Professor at the University of Texas Medical School at Houston, she spent four years as a postdoctoral research fellow at the University of Michigan.

Per Dr. Ivanciu, the JGP award was the starting point of her career in the field of hemophilia. By receiving this award, she was able to advance her understanding of bleeding disorders and gained the necessary experience in state-of-the-art techniques in animals, molecular biology and biochemistry of clotting factors. All of this has prepared her for the next phase of her career.

The objective of this study is to collect a large data base of gait parameters on individuals from the age of 12 months to 99 years old who do not have neuromotor deficits. This ongoing study will be the basis of comparison for people with hemophilia as a means to identify gait deficits that occur due to joint or muscle involvement from the bleeding disorder as compared to gender and age matched controls. We are using the GaitRite electronic walkway evaluation system as the quantitative measurement tool for gait analysis. Enrolled subjects are consented to this study and to the storage of data in a gait repository for future studies. This data will be available to other Hemophilia Treatment Centers upon written request to our Gait Repository Guardian (currently Dave Oleson, PT at the Hemophilia Treatment Center at CDRC in Portland, OR).

Menstrual cycles for females with bleeding disorders can present special challenges not experienced by other girls and women. Having your period can be physically, social and emotionally exhausting. A new web-based application is now available and can be downloaded to your personal mobile device or desktop computer. With this application you can track how long your period lasts, how much you are bleeding, any interventions utilized and how it is affecting your daily life. This is a new web-based application you can download that is free and available to all girls and women with bleeding disorders through their federally funded hemophilia treatment center (HTC).

Individuals with hemophilia are living longer than previously expected because of advances in treatment, including the development of clotting factor replacement. However, we do not understand the psychological and emotional impact of aging with hemophilia, how this affects quality of life, and how resilience and healthy coping skills are developed and maintained. For example, we do not know if persons with hemophilia: (a) retire early because of having a disability, although this may be a reasonable assumption; (b) if they are financially secure; and (c) how much joint damage impacts the ability to move, walk, and perform everyday activities. We also do not know what special challenges arise from aging with hemophilia, and if this leads to more divorces, an increase in living alone, and a greater need for help to remain independent. There is little research showing which traits help persons with hemophilia continue to mature, and keep an emotional balance while dealing with a lifelong, chronic condition and how all these traits improve or reduce quality of life.