UAMS lands $1.54 million research grant for brittle bone disease

The University of Arkansas for Medical Sciences (UAMS) has landed a $1.54 million research grant to study better treatments for osteogenesis imperfecta (OI), also known as brittle bone disease.

The four-year award from the National Institutes of Health will support Roy Morello, Ph.D., and his interdisciplinary team to test whether lung abnormalities in OI patients can be treated separately from OI’s bone-related defects.

An estimated 25,000 to 50,000 people in the United States live with OI, a rare genetic disorder of connective tissues that has no cure. It is mainly caused by mutations in the genes responsible for producing Type I collagen, a protein that normally holds bones together and makes them strong. With inadequate collagen, bones become brittle and prone to fractures.

“Collagen is a primary building block for bones, and OI is like the perfect storm for the skeleton,” said Morello, associate professor in the College of Medicine departments Physiology & Cell Biology, Orthopaedic Surgery, and the Division of Genetics.

OI also plagues other organs and tissues, including the lungs, skin, teeth and heart, and it affects hearing. In severe cases, the disease can be lethal in infants.

“Collagen really covers a broad spectrum of issues that these patients unfortunately are subjected to,” Morello said. “There is obviously a desperate need for new therapies.”

The impact of OI on respiration has long been thought to result from the OI-caused bone issues, such as chest wall deformities and abnormal spine curvature, but recent studies by Morello’s team challenge that view. The findings have led to their hypothesis that respiratory defects in OI patients could be treated separately from their skeletal fragility.

“We were among the first to show that there were primary changes in the lung caused by mutations in Type I collagen,” Morello said. “This is a completely new model to study the disease, and it should lead us to a much better understanding of OI,” he said. “Our long-term goal is to identify new treatments for the respiratory disease and prevent disability and death from OI.”

Collaborators on the research project include John L. Carroll, M.D., a professor and section chief for the Pediatric Pulmonary and Sleep Medicine Division in the College of Medicine Department of Pediatrics.

Other collaborators are:

Intawat Nookaew, Ph.D., associate professor, College of Medicine Department of Biomedical Informatics
Milena Dimori, Ph.D., DVM, research associate and lab manager
Anne-Karina Perl, Ph.D., Cincinnati Children’s Hospital Division of Pulmonary Biology
Sergey Leikin, Ph.D., senior investigator, NIH Section on Physical Biochemistry