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$10 Million Grant Awarded to Medical College for Genetic Studies of Common Bleeding Disorder

March 14, 2012

The Medical College of Wisconsin has received a five-year, $10 million National Heart, Lung and Blood Institute Program Project Grant to continue genetic studies that seek to improve the molecular and clinical understanding of Von Willebrand disease (VWD), the most common hereditary bleeding disorder.

Pediatric hematologist Robert R. Montgomery, M.D., professor of pediatrics at the Medical College, senior investigator at the Blood Research Institute of the BloodCenter of Wisconsin, and pediatric hematologist at Children’s Hospital of Wisconsin, is principal investigator for the grant.

Von Willebrand disease is caused by a deficiency of von Willebrand factor (VWF), which is necessary for normal blood clotting. The disease affects both men and women. Most cases are mild, but aspirin and other nonsteroidal anti-inflammatory drugs can make the condition worse. Women may suffer very heavy menstrual bleeding, and family history of a bleeding disorder is the primary risk factor.

“There is a lack of understanding of the genetic causes of low or abnormal VWF, and the molecular mechanisms involved in the disorder,” says Dr. Montgomery. “While a large number of individuals have low VWF with abnormal bleeding symptoms, it is not scientifically clear if this is a disease, or if VWF is a continuous risk-factor for bleeding. For many practicing physicians, the general understanding of this group of disorders has not been optimal, and how to evaluate and treat these patients has been unclear.”

This study will determine the clinical and genetic characteristics of a large number of VWF patients as well as carriers of genes for various forms of the disease. The researchers will also explore the impact specific combinations of these genes and unrelated genetic mutations may have on individuals and families.

Dr. Montgomery’s co-investigators at the Medical College and Children’s Hospital of Wisconsin are: Sandra L. Haberichter, Ph.D., associate investigator at the Blood Research Institute and associate professor of pediatrics (hematology/oncology); Joan Cox Gill, M.D., professor of pediatrics (hematology/oncology) and Director of Comprehensive Center for Bleeding Disorders at the BloodCenter of Wisconsin; Raymond G. Hoffmann, Ph.D., professor of biostatistics in pediatrics; Veronica H. Flood, M.D., assistant professor of pediatrics (hematology/oncology); and Kenneth D. Friedman, M.D., associate professor of medicine (hematology/oncology) and Director of Hemostatis Laboratory and Medical Director at BloodCenter of Wisconsin.

In addition, there are seven primary clinical centers (Milwaukee, Atlanta, Detroit, Pittsburgh, New Orleans, Indianapolis, and Iowa City) and more than 25 secondary clinical centers throughout the United States that recruit research subjects and send the samples to Milwaukee for the specialized testing. More than 600 families have been recruited for this project.

The program project grant mechanism is designed to support synergistic research, in which the funding of several interdependent projects as a group offers significant scientific advantages over supporting these projects as individual research grants. This multinational grant is facilitated by teamwork between the Medical College of Wisconsin, BloodCenter of Wisconsin and Children’s Hospital of Wisconsin, who oversee subcontracts to Queens University in Canada and University of Sheffield in the United Kingdom.

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