Efforts to find a cure for Fibrodysplasia Ossificans Progressiva (FOP), an extremely rare disorder that causes bone to form outside the skeleton, could transform the lives of people living with the condition and provide for the treatment of more common diseases caused by a similar problem. faulty mechanism, says one of the leading doctors studying FOP news week.
FOP, a congenital condition, is a progressive condition in which ribbons, sheets, and plates of bone eventually replace muscles and connective tissues, according to Dr. Frederick Kaplan, the Isaac and Rose Nassau Professor of Orthopedic Molecular Research at the Perelman School. from the University of Pennsylvania. of Medicine.
“Eventually, these episodic transformations, which we call flare-ups, form a second skeleton that completely immobilizes the entire body and makes movement impossible,” says Kaplan, who estimates he has met 90 percent of the roughly 1,000 patients worldwide with FOP.
“It’s a catastrophic disease that robs patients of their independence as they grow older.”
The condition, which affects only one to two people per million, occurs when people inherit an abnormal copy of the ACVR-1 gene, which is involved in normal bone formation. Children born with FOP may inherit the abnormal copy of the gene from one parent, or through a spontaneous mutation in the gene while developing in the womb, according to Focus on FOPa website developed by Ipsen Biopharmaceuticals Inc. in collaboration with those living with FOP and the health professionals who care for them.
Clutter Appears With Little Warning
Children born with FOP appear normal at birth, with the exception of a telltale malformation of the big toe, which tends to be shorter and pointed inward. Generally, between the ages of two and five, most develop swelling in the head, scalp, neck or back, says Kaplan.
In its early stages, the disease is often misdiagnosed as an aggressive tumor, he adds; instead, it is normal bone, which simply forms in the wrong place at the wrong time.
FOP tends to progress more rapidly in adolescence, where it comes in waves. Although most flare-ups are spontaneous, they can be caused by injury, biopsy or intramuscular injection, Kaplan says; some research suggests that the immune system is a trigger. Generally, by the age of 30, patients are completely immobilized by sheets of extra bone that prevent them from moving, with the result that many require assistance with activities of daily living.
Although FOP does not affect the internal organs, apart from crowding them, it compresses the chest wall and prevents it from expanding, which can lead to spinal deformity. Eventually, the restricted chest wall can contribute to heart failure, says Kaplan. The estimated median lifespan for those living with FOP is around 56 years.
Erin Danzer, 24, was diagnosed with FOP as a baby and careful management of her condition meant she was able to put off the rapid progress of the condition until her late teens.
“It’s something I’ve had to live with all my life and luckily I was diagnosed correctly at a very young age,” he says. news week. “So, growing up, my parents made sure that I was very careful and aware of my physical limitations and that I didn’t participate in any physical activities.”
Because his FOP did not progress rapidly at such a young age, as is the case for many FOP patients, Danzer maintained his mobility and was able to walk and even jog until he was 19 years old. Because her FOP was not noticeable while she was in school, she forgot to share her condition with others.
“I felt normal, despite the limited range of motion in my arms, shoulders and neck. And I wanted to be normal,” she says. “When I had my first big outbreak that took away my ability to walk at 19, I started to open up about it. Because now it was very clear that I had a disability and it was no longer something I could hide.”
Danzer describes that bout, which lasted almost two years, as the worst experience he has ever had to deal with, adding, “It really broke my confidence and I contemplated a lot about all the things I lost because of FOP, mainly my independence.”
Over the past five years, Danzer has started working, revamped his social life with friends, and adapted to doing things differently. After an outbreak in her jaw two years ago, her ability to eat was affected, limiting her diet to mostly soft foods, such as shakes and protein shakes.
“I still have little flare-ups from time to time, but nothing has been serious enough to make me lose mobility,” she says. “FOP is so unpredictable so I take it one day at a time and I appreciate today being a good day.” be involved with the FOP communityfundraising and reaching out to others with the disease are especially beneficial, she says.
Focusing on the future
Since the ACVR-1 gene mutation was discovered in 2006, efforts to develop a treatment have accelerated, Kaplan says. Thirty pharmaceutical and biotech companies have expressed interest and around 16 are actively developing drugs for clinical trials. At least six clinical trials for adults are currently underway.
For pharmaceutical companies, says Kaplan, rare diseases like FOP are a challenge in their own right and are attractive to study because they reveal seminal signaling pathways that drugs can target, which can also be used to treat more common conditions, such as hip and joint deterioration.
“We are just beginning to enter the era of clinical trials with small molecules that can inhibit extra bone,” he adds. “Some of these methods to inhibit an overactive pathway will help other researchers.”
Correction 08/03/22, 12:33 pm ET: Correct Focus On FOP website description