NIH grant will support collaborative hemophilia A study

The study of 50 mothers and sons will trace the roots of risk for immune factors that can complicate treatment of the bleeding disorder. 

Hemophilia A is a rare genetic bleeding disorder that affects approximately one in 5,000 live male births. It is caused by a missing or abnormal clotting protein, factor VIII, so the disease is also known as factor VIII deficiency. The frequency and intensity of bleeding episodes related to hemophilia A generally correlates with the severity of deficiency of factor VIII.

The most common treatment is factor VIII replacement. While this approach helps a person with hemophilia A to clot, the infusion also can trigger harmful immune responses called inhibitors. This, in turn, can make treatment less effective, with more bleeding and poorer quality of life.

Currently, both risk factors for immune complications and the mechanisms that drive them are not completely understood. These unknowns are the focus of a National Institutes of Health-funded research effort based at the University of Washington School of Medicine.  

A new initiative called Hemophilia A Analytical Cohort Research Program (HARP) will be led by Dr. Jill Johnsen, a UW associate professor of hematology and researcher at Institute for Stem Cell and Regenerative Medicine.

Johnsen and research colleagues will trace the roots of risk for immune complications, starting from the time in the womb. The investigators plan to follow fifty pairs of mothers who have the gene change that leads to factor VIII deficiency and their babies who have severe hemophilia A.

“Through the longitudinal study design, we have the opportunity to watch the human immune system evolve in ways that haven’t been seen before,” Johnsen explained. “We’re going to study the pregnancy, follow each mother through her delivery, and then follow the mother and baby as a bonded pair for the first years of life. We’ll be collecting blood samples and data as the babies live their lives and are treated for hemophilia, all the while tracking who makes an inhibitor that causes the body to react to the FVIII replacement treatment and who does not.”

Co-leading the HARP are Dr. Shannon Meeks, a pediatric hematologist and immunology researcher at Emory University, and Grier Page, a senior fellow and senior director of statistical genetics and artificial intelligence at RTI International.

The team aims to build the program and advance scientific studies in four areas: maternal biology, perinatal biology, the newborn, and immune system development in early life.

The resulting data should help scientists and physicians better predict a patient’s inhibitor risk and develop an individualized treatment plan to mitigate the immune response or point them to an alternative therapy.  

“We believe if we can better understand why inhibitors develop in some people but not others, we should be able to identify more effective tests and interventions for patients,” Johnsen said.

The researchers will be supported by a grant from the National Heart, Lung, and Blood Institute.  The HARP award’s first phase is a three-year, $6.6 million grant, with four additional years in a proposed second phase.

– Written by Thatcher Heldring, Institute for Stem Cell and Regenerative Medicine

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