Research Needs
What Needs to Be Done
The FOP gene discovery is relevant to every disease that affects the formation of bone and every disease that affects the formation of the skeleton. Answers to FOP are relevant to many common skeletal conditions such as unwanted bone growth that forms after hip replacement surgery, athletic injury, brain injury, spinal cord injury, soft tissue injury, burns, war wounds, valvular heart disease, and even bone spurs from osteoarthritis. Eventually, through progress being made in FOP research, much of which has been highlighted in this Eighteenth Annual Report, it might be possible to harness the FOP gene, and create bone in a more controlled way where it is desperately needed such as in fractures that do not heal, surgical spine fusions, severe bone loss from trauma, osteoporosis, tumors, and congenital malformations. The FOP gene discovery is a great beacon of hope for all of us in the FOP community, and for millions in a much wider global community who are affected with common skeletal disorders such as osteoporosis, fractures, and bone cancer. Better treatments for FOP are not just a dream – they are now likely, and a cure is a distinct possibility.
During the past several years, we have begun to turn the FOP gene discovery into insight, and insight into development. We have set our sights on the distant horizon. But, we won’t get there by wishing it, and we cannot do it alone. We continue to need your help.
- We have continued to expand the network of physicians and scientists who are working on FOP through targeted identification and funding of those who can help most and of those who can help the fastest – wherever they may be. In 2008, we funded our first international collaborative research grant at the laboratory of Dr. Petra Seemann in Berlin, Germany who is performing groundbreaking experimental work on the developmental effects of the FOP gene. Importantly, we are funding the first collaborative development of novel ACVR1 inhibitors in the laboratory of Dr. Charles Hong at Vanderbilt University. We need to expand these programs and others like them, and we need your help.
- We have continued to develop cellular and animal models to determine how the renegade FOP gene acts at the molecular level. We now have a chimeric animal model for FOP and several animal models that have features of FOP. We need those critical models to design new drugs and to test them, and we need germline transmission and larger animal colonies to accomplish those goals. We need to continue that work, to expand it, and we need your help.
- We have continued to crystallize the mutant FOP protein to study its atomic structure, its catalytic domains, and its interactions with other co-conspiratory proteins in the molecular switch that is detonated to form catastrophic new bone formation. Such knowledge will be needed to custom-design the best medications to block the mutant switch. We need to continue that work, to expand it, and we need your help.
- We have continued to model the mutant ACVR1 receptor, the so-called “fuse” of the FOP “hydrogen bomb.” We are beginning to use that knowledge to design the best methods to block, jam, and bypass it. We need to continue that work, to expand it, and we need your help.
- We have identified the inflammatory detonator of the mutant FOP receptor and have begun to probe the mechanisms by which the inflammatory microenvironment of an injury detonates the receptor to form heterotopic bone. When we truly understand that complex molecular mechanism, we’ll be able to use that knowledge to inhibit the chain reaction. We need to continue that work, to expand it, and we need your help.
- We have begun to scour the world’s available libraries of medicinal compounds to identify those that may block the abnormal FOP switch and its downstream molecular circuits. We have identified one such class of compounds that is under intense investigation. We need to continue that work, to expand it, and we need your help.
These goals and the tasks they support are easy to articulate and all have been started, but they need continued funding to be fulfilled. These are challenging financial times for all, but we need your help to continue these vital programs and ensure their success, to do more, to do it faster, to expand our horizons, and to make sure that no clue is ignored. It could be the clue that leads to a cure.
Our research budget of $1.5 million annually supports a core laboratory of 15 scientists as well as collaborators around the world. Each year, we struggle to find the funds to persist. But we need to do more than persist. We need to prevail. We need your help.
FOP is an uncommon condition of uncommon brutality, but there is finally a chance to do something intelligent and rational to interrupt the inexorable progression of what has been described as a “horrible nightmare disease.” Chemistry combined with compassion will lead to orphan drug development, to more effective treatments for those with FOP, and for those with more common forms of heterotopic ossification. We have worked hard to get this far, and your generosity has helped get us there. But, we need your help to go farther. We all know what needs to be done, and we need your help to prevail.
As we have said many times, cause and cure are the two words that propel us and provide the guiding principle for all we do: to discover the cause of FOP, and to use that knowledge to develop effective treatments and eventually a cure. Many said that identifying the gene mutation that causes FOP couldn’t be done. In 2006, with your commitment and generosity, we reached the summit of a great mountain and discovered the genetic cause of FOP. In 2007, we headed for a higher and more distant summit – the treatment and cure of FOP. In 2008, we have made great progress in our journey to that summit. We need to continue that journey, to expand it, and we need your help.
What needs to be done? As David Ben Gurion, the first Prime Minister of Israel said, “The difficult we do immediately; the impossible takes a little longer.” With your help, we plan to do the impossible, not just climb mountains, but also move them. Finding an effective treatment and cure for FOP is not a job; it is a mission.
