Friends With FOP

Posted by Karen

This week, the “19th Annual Report of the Fibrodysplasia Ossificans Progressiva (FOP) Collaborative Research Project” was released to the public.  This year’s report was written by Dr. Fred Kaplan, Dr. Robert Pignolo and Dr. Eileen Shore of the University of Pennsylvania.  While much of the work they describe was carried out at the authors’ own lab (colloquially known as the “FOP Lab”), the title of the report reflects that a  number of different research projects took place in locations around the world by various scientists.

I like reading this report every year.  It’s written for a lay audience, so is (mostly!) understandable and gives a good perspective on what steps were taken in the previous calendar year to advance the understanding of FOP and work toward a cure.  Just like I did last year with the 18th such report, I’m going to take a stab at summarizing this document.  If, however, you want to read the report in full yourself, go to www.ifopa.org and click on the link indicated on the web page. 

On page 3 of the report, the authors note, “The conclusion to the film was pre-determined by the discovery of the FOP gene (the fuse of the nuclear bomb) in 2006.  In 2008, we got our first glimpse of how the bomb was triggered.  In 2009, we used the first crude tools to try to disarm it.”  (NOTE – the “film” referred to is an extended metaphor used in the report of a movie about detonation of a nuclear bomb, with the bomb being of course FOP.)  This was the most exciting thing in the report, as far as I’m concerned. 

In fact, the writers comment that they have formulated 4 different possible approaches to “disarming the FOP bomb” (page 16), which include:

1. Blocking the activity of the mutant FOP receptor (disarming the fuse of the renegade nuclear weapon).

2. Blocking the inflammatory triggers (blocking the trigger of the bomb).

3. Blocking the responding connective tissue progenitor cells (inhibiting the working components of the bomb from orchestrating the explosion).

4. Altering the micro-environment that promotes heterotopic ossification (changing the conditions that lead to the explosion).

The scientists go on to indicate that in researchers around the world are focused on each of these approaches.

For instance, the authors indicate that in 2009, scientists began testing a family of pharmaceutical compounds which have the ability to block the FOP gene.  Apparently the first such substance they tested blocks the gene effectively, but is too toxic to other body systems.  However, the authors report that more selective and refined compounds are being identified and/or created which look promising in terms of affecting the FOP gene without causing intolerable side effects (page 17).

This is so fantastic to read about.  I know it’s early days yet, but it’s wonderful to learn that the scientists really are making progress on the “holy grail” of FOP research, the quest for a cure or effective treatment for FOP.

That part of the report is exciting to read, but there’s other good stuff in there too.  Here’s my little grab bag of  summaries of what’s in the report…

- The scientists at the FOP Lab worked together with Dr. Mary Mullins, a progressor of cell biology, to study how FOP develops at a molecular level.  As a result of this study, they learned a great deal about the specific set of cellular changes involved in FOP flare-ups.  They used an animal called a zebrafish in this study.  Scientists in the Netherlands also studied this subject, and produced an article describing the process of cell differentiation in FOP.

- Early studies into the involvement of oxygen in FOP flare-ups are showing that FOP cells react differently to a low oxygen environment than to normal cells.  This is said to have “important clinical implications for the formation and prevention of FOP lesions.” (page 9)

- The scientists at the FOP Lab wrote a paper about a study they conducted which revealed that the bone-forming cells which lead to new FOP bone originate in blood vessels.  This was a new and unexpected finding.

- Researchers at the FOP Lab also learned the identity of certain “helper cells” which assist the FOP gene in doing its dirty work.

In addition to explaining these studies, the report also talks about the “FOP zoo”, a set of animals which are proving to be invaluable to FOP research.  These animals include the zebrafish, chicken, engineered FOP “chimera” mouse and the fruit fly.

After describing the work done during the previous year, the authors go on to describe the various presentations they had made and conferences they had attended, as well as other relevant events.  One such occasion was the “mothers’ tour” of the lab which occurred at the end of the FOP mothers’ retreat in June of 2009.  A really terrific thing about the FOP Lab is the openness of the scientists to having FOP patients and their familes tour the lab and learn about what’s going on, and the scientists were at their most welcoming when the moms visited.  I know, because I was there!  The report even quotes yours truly when I gave a thank you speech after the tour (SO cool to see my name in print, even though my surname was incorrectly stated as my daughter Miranda’s surname, Friz…  it’s correctly indicated in the accompanying picture as Munro )  I said, “Drs. Shore and Kaplan took us all around the lab and showed where everything is done.  This was another emotional experience, and again there were lots of tears flowing.  I think it is fair to say we all felt the same thing: an immense and awestruck gratitude that these people are working so hard for a treatment for the rare and terrible disorder that affects our kinds.  I will never forget this tour.” (pages 22/23)

Here are all the moms and all the scientists posing for a photo. That's me with the bright blue striped T-shirt and glasses.

To all the scientists who study FOP – thank you again, and again, and again for all your hard work.

Erin McCloskey and my daughter, Miranda Friz... Two very special little girls who will benefit from the hard work by FOP scientists.

Miranda and another friend with FOP, Brooke Connell.