Breakthrough For Rare Orthopedic Genetic Disorder; Broad Implications For Orthopedics
BY ARIELLA P. GOLOMB, MD, JUNE 9, 2006
A Single Codon Mutation Causes A Debilitating Disease
Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant genetic disorder that causes muscles and other connective tissue to turn into bone and is estimated to affect one in two million patients worldwide. When the disease progresses, it causes immobility as bone fuses joints. In essence, FOP patients begin to develop a second skeleton, the only known example of one normal organ system turning into another.
Thanks to the pioneering work of Fred Kaplan, MD and Dr. Eileen M. Shore, PhD, and other scientists in the International FOP Research Consortium, patients with this disease have new found hope. In the May 2006 edition of Nature Genetics this team of scientists describes the cause of FOP: a single amino substitution in the Activin Receptor Type IA (ACVR1) protein, a bone morphogenic protein (BMP) receptor. This mutation represents a highly specific target for future drug development to cure FOP, not merely a treatment of the symptoms. The next step is to develop an animal model with the same mutation in ACVR1 that is found in people with FOP.
The identified FOP mutation is one of the most specific codons in the human genome to be associated with a disease phenotype. Achondroplasia and Timothy Syndrome are two additional disorders mainly associated with mutations in a single condon.
Broad Implications For Orthopedics
As Dr. Kaplan explains, the future transition of the scientific understanding from the genetic to molecular level will shed light on the treatment of FOP. It will also help explain "conditions such as non-genetic forms of extra bone growth that may occur following total hip replacement, head injuries, spinal cord injuries, sports injuries, blast injuries from war, and even osteoarthritis and damaged heart valves. Perhaps someday we will be able to harness the gene mutation that causes the renegade bone formation in FOP and make bone in a controlled way - for patients who have severe osteoporosis, for those with severe bone loss from trauma, for those with fractures that fail to heal or spinal fusions that are slow to heal, or for those with congenital malformations of the spine and limbs. We have reached a summit on our epic journey to understand FOP - knowledge we desperately need to help the kids and that will likely help many others. We still have a long way to go, but finally we can see a therapeutic horizon above the clouds, and the view is promising."
Supporting Basic Science Research Funding
We applaud the research team on this project who dedicated the last 15 years to the identification of a cure for a crippling disorder that imprisons an estimated 2,500 children. Their success reinforces the need to focus on and fund basic science research so that breakthroughs of this caliber can continue.
