Penn, CHOP researchers find major clue to crippling genetic disorder

by Marie McCullough

Published Apr. 18, 2016, 9:04 a.m. ET

Imagine a disease that turns your muscles, tendons, and ligaments into bone, progressively crippling you and interfering with such basic functions as eating and breathing. Any attempt to surgically remove the extra bone triggers explosive new growth.

The inherited disease that actually causes that nightmare scenario, fibrodysplasia ossificans progressiva (FOP) is, thankfully, very rare, afflicting about 2,500 patients worldwide. Now, they have reason to celebrate: Researchers at Children's Hospital of Philadelphia and the University of Pennsylvania have taken a big step toward finding a drug to treat or even prevent FOP.

In young laboratory mice bioengineered to carry the defective FOP gene, the researchers showed that the drug, called palovarotene, prevented abnormal bone formation, maintained limb mobility, and restored normal bone growth.

"If these results translate to humans, we may be able to treat children with FOP early in life, before the disease progresses," Children's researcher Masahiro Iwamoto, a senior author of the study, said in a press release.

Palvarotene is in a class of drugs that targets molecules involved in cartilage formation. It was originally developed and evaluated by Roche Pharmaceuticals to treat emphysema. When it showed no benefit for that purpose, Roche licensed the drug to biotech start-up Clementia Pharmaceuticals, which is currently conducting an international study to see whether the drug helps prevent FOP flare-ups in children and adults.

The leader of that international study is Penn orthopaedic medicine specialist Frederick S. Kaplan, who has spent much of his career studying FOP. In 2006, he announced the pivotal discovery of the genetic defect that prompts a bone-making protein to go awry in FOP. Kaplan was a co-author of new study, published online last month in the Journal of Bone and Mineral Research.

In 2011, the researchers showed that palvarotene was protective in animals bioengineered to grow the kind of abnormal bone that occurs after a traumatic injury.

Kaplan and his colleagues have stressed that while FOP affects relatively few people, undertanding it has implications for treating trauma, osteoporosis, fractures, bone malformations and joint damage.