For the past five years, Baylor College of Medicine has received funding from the National Institutes of Health to lead the Brittle Bone Disorders Consortium of the Rare Disease Clinical Research Network. The goal has been to advance the study and treatment of osteogenesis imperfecta, a genetic disorder affecting both children and adults characterized by brittle bones that break easily. The NIH has awarded a $7 million grant to fund the BBDC for five more years.
“The formation of the consortium has been transformational in furthering OI research,” said Dr. Brendan Lee, Brittle Bone Disorders Consortium (BBDC) principal investigator and professor and chair of molecular and human genetics at Baylor. “With this new funding, we will be able to continue learning about this disorder and finding better ways to treat those who are living with it.”
The BBDC aims to better understand all genetic forms of OI, expand treatment options and train the next generation of physicians and scientists to study and treat this disorder. Baylor College of Medicine serves as the lead site of the 14-center BBDC. Other BBDC clinical centers include Shriners Hospital for Children, Montreal/McGill University; Oregon Health and Science University; University of California Los Angeles; Kennedy Krieger Institute; Children’s National Medical Center; Hospital for Special Surgery; Shriners Hospital for Children, Chicago/Marquette University; University of South Florida/Shriners Hospital for Children, Tampa; University of Washington; Osteogenesis Imperfecta Foundation; University of Nebraska Medical Center; and Alfred I. duPont Hospital for Children.
As part of the goal to better understand OI, Baylor researchers are leading a longitudinal study to map out the natural history of the disease. In the last five years, the BBDC has enrolled nearly 1,000 patients in North America to study disease progression. That includes examining the effect of the current standard-of-care treatment — IV medications called bisphosphonates. Researchers also are studying craniofacial and dental disease and pregnancy complications stemming from osteogenesis imperfecta.
“We are delighted to receive funding to continue our longitudinal study,” said Lee, the Robert and Janice McNair Endowed chair and director of Center for Skeletal Medicine and Biology at Baylor. “The next round of our study will focus more on quality of life measures. We want to make sure that when we give a therapy, it doesn’t negatively impact the patient’s quality of life.”
BBDC research has led the way to the first therapy that targets the cause of brittle bone disease, rather than the consequencees. Baylor researchers found that activation of TGF-β, a protein important in bone formation, is a common factor among osteogenesis imperfecta patients. A phase I clinical trial currently is testing fresolimumab, an antibody that targets TGF-β, and can lead to higher bone mass, quality and strength.
The BBDC will also use the new funding to start the first-ever orthodontic interventional trial in OI. Patients often have severe orthodontic problems that can impact their ability to eat. But due to the fragile nature of their teeth, they cannot use traditional metal braces. The BBDC clinical trial will test whether clear aligner treatment can improve dental function.
Part of the BBDC mission includes working with OI patient support groups to help those patients who wish to be involved in research connect with those doctors conducting the research. The Osteogenesis Imperfecta Foundation helps facilitate this goal.
“We at the Osteogenesis Imperfecta Foundation are thrilled to be a part of the Brittle Bone Disorders Consortium once again,” Osteogenesis Imperfecta Foundation CEO Tracy Hart said. “Our first five years as the advocacy partner of the BBDC proved very successful. We were able to use the data collected to make significant changes in the way we provided information to our constituents and benefitted greatly from the collaboration with the principal investigators at all of the BBDC sites.”
Baylor College of Medicine also participates in several other consortia of the Rare Disease Clinical Research Network that the NIH has funded for another five years. Those include in the Consortium of Eosinophilic Gastrointestinal Disease Researchers, the Dystonia Coalition (BCM PI Dr. Joseph Jankovic), the North American Mitochondrial Disorders Consortium (BCM PI Dr. F. Scaglia), the Primary Immune Deficiency Treatment Consortium (BCM PI Dr. Imelda Hanson), and the Urea Cycle Disorders Consortium (BCM PIs Drs. S. Nagamani and L. Burrage). Newly funded consortia that also involve Baylor include the Global Leukodystrophy Initiative Clinical Trials Network (BCM PI Dr. L. Emrick), and the Frontiers in Congenital Disorders of Glycosylation (led by BCM PI Dr. F. Scaglia). Find a full description of these consortia.