Children with multiple hereditary exostoses (MHE), a rare inherited disease, suffer from multiple growths on their bones that cause pain, disfigurement, and stunted growth. At the moment, the only treatment is surgery to remove the growths, which sometimes number in the hundreds.

“MHE is not usually deadly, but it is debilitating,” said Dr. Yu Yamaguchi, professor in the Sanford Children’s Health Research Center at Sanford-Burnham. “And if not removed by surgery, there is a chance these bone growths will become cancerous.”

MHE research has long been hampered by the lack of a good model that would answer questions about the underlying cause and allow scientists to test new treatments. Today in the journal Proceedings of the National Academy of Sciences, Dr. Yamaguchi and his collaborators unveiled a mouse model that does just that.

“This research is profoundly important,” said Sarah Ziegler, vice president of the MHE Research Foundation, which has provided seed funding for Dr. Yamaguchi’s research.  “My son had more than a 100 of these tumors and has gone through 15 surgeries. When your child has such a debilitating condition, and you know there’s nothing you can do, it’s petrifying. With this model, researchers can start looking for a cure.”

Earlier attempts at creating a mouse model of MHE successfully replicated the human disease on a genetic level, but failed to reproduce the symptoms. In this new study, Dr. Yamaguchi and colleagues, including Sanford-Burnham scientists Dr. Kazu Matsumoto and Dr. Fumitoshi Irie, took a different approach. Instead of deleting the gene in the entire mouse, they targeted the gene in only bone cells. What’s more, they removed the gene in only a small fraction of these cells.

Surprisingly, this approach led to a mouse with all the symptoms of MHE, including bony protrusions, short stature and other skeletal deformities. Further investigations into the cellular make up of the bone growths answered some long-standing questions about how they develop.

“This new mouse system also provides a platform for screening potential drugs that inhibit bone growths in MHE,” Dr. Yamaguchi explained. “We are currently developing chemical inhibitors to block their formation.”