Yesterday it was muscles and connective tissue, today suddenly bones - what sounds as if taken from one of Franz Kafka's disturbing novels is experienced as a cruel reality by people affected by Fibrodysplasia Ossificans Progressiva (FOP). Due to a genetic disorder, their bodies do not form scar tissue when wounds heal; instead, they form bone. Even minor injuries can cause joints to suddenly become immobile and the body to slowly stiffen. In view of new successes in basic research, the about 800 patients worldwide may have new hope. On February 27, 2020, Eva Luise Köhler will awarding Prof. Dr. Martina Rauner and Dr. Ulrike Baschant from the Medical Faculty of the Technical University of Dresden for a promising new therapeutic approach that could inhibit the progressive ossification. With the award money of 50,000 euros, they will work with an international team to test the mode of action of a recently discovered protein that inhibits excessive bone formation in genetically modified FOP mice.
Early diagnosis and guidance by experienced doctors who are familiar with the right treatment strategies can save a lot of unnecessary suffering, explains Nadine Großmann, who received her FOP diagnosis at the age of 13. For example, she says, many doctors do not know that surgical procedures must be avoided at all costs because they can trigger massive bone spasms. A jaw operation had dramatic consequences for her, after which she was only able to open her mouth 2 mm within a few days. The next disease episode spontaneously stiffened her right shoulder.
"And that makes me lucky," explains the young biochemist, who is currently also researching molecular signal transmission in FOP as part of her doctoral thesis at the FU Berlin/ Charité. Often, by the end of puberty, all joints close to the trunk are fixed in patients with FOP, so that they can only move around in a wheelchair and are dependent on outside help.
A surprising therapeutic approach
In their search for therapeutic options that could specifically inhibit the progressive ossification of connective tissue, scientists in the "Bone Lab" at the TU Dresden last year also investigated the interaction between iron and bone metabolism - two systems that at first seem unrelated. The fact that transferrin receptor-2 (Tfr2) of all things - a protein molecule that is predominantly formed in the liver and is responsible for iron transport - turned out to be an extremely effective regulator in the derailed bone metabolism of FOP cells surprised even Martina Rauner, who has dedicated herself to the study of rare bone diseases for years: "When we saw how potent the binding region of Tfr2 was in inhibiting unwanted ossification, i.e. excessive bone growth, it was clear to us that this discovery had potential for further clinical development. "
Eva Luise Köhler awards the research award named after her on 27th February 2020
The fact that the results could be significant not only for patients with FOP, but beyond that for other indications as well, is explained by Prof. Dr. Annette Grüters-Kieslich, Chairman of the Foundation: "Even in patients without an ACVR1 mutation, for example after the implantation of hip joint endoprostheses, ossification of the surrounding tissue is a common complication that can lead to permanent pain and movement restrictions. As often, rare diseases teach us what treatment strategies might look like for common diseases as well."
"The confidence and energy with which the patients not only master their challenging fate, but actively work to advance FOP research and increase knowledge about this extremely rare disease, impresses and touches me deeply," commented the former First Lady and patron of the Alliance of Chronic Rare Diseases (ACHSE) e. V. on the commitment of the patient representatives.
The Eva Luise Köhler Research Award for Rare Diseases is awarded for the 13th time in collaboration with ACHSE e. V..
Detailed information about the research project, the award winners and FOP can be found in our Hintergrundinformationen.