FOP, a congenital condition, is a progressive condition in which ribbons, sheets and plates of bone eventually replace the muscles and connective tissues, according to Dr. Frederick Kaplan, Isaac and Rose Nassau Professor of Orthopedic Molecular Research at the University of Pennsylvania’s Perelman School of Medicine.
“Eventually, these episodic transformations, which we called flare-ups, form a second skeleton that completely immobilizes all the body and makes movement impossible,” says Kaplan, who estimates that he has met 90 percent of the approximately thousand patients around the world with FOP.
“It’s a catastrophic disease that steals independence from patients as they are growing.”
The condition, which affects only one or two people per million, is caused when people inherit an abnormal copy of the ACVR-1 gene, which is involved in normal formation of bone. Children born with FOP can inherit the abnormal copy of the gene from a parent, or via a spontaneous mutation in the gene while developing in the womb, according to Focus On FOP, a website developed by Ipsen Biopharmaceuticals Inc. in collaboration with those living with FOP and healthcare professionals who care for them.
Disorder appears with little warning
Children born with FOP look normal at birth with the exception of a telltale malformation of the big toe, which tends to be shorter and pointed inwards. Generally, between two and five years of age, most develop swelling on their heads, scalp, neck or back, Kaplan says.
In its early stages, the disease is often misdiagnosed as an aggressive tumor, he adds; instead, it is normal bone, just forming 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 injuries, biopsies or intramuscular injections, 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 make it impossible to move, with the result that many require assistance with activities of daily living.
Although FOP doesn’t affect internal organs, other than crowding them, it compresses the chest wall and prohibits it from expanding, which can cause spinal deformity. Eventually, the restricted chest wall can contribute to heart failure, Kaplan says. The estimated median life span for those living with FOP is around 56.
Erin Danzer, 24, was diagnosed with FOP as an infant and careful management of her condition meant that she managed to put off rapid progress of the condition until her late teens.
“It’s something I’ve had to live with my whole life and thankfully, I was properly diagnosed very young,” she tells Newsweek. “So, growing up, my parents made sure I was very careful and aware of my physical limitations and to make sure I didn’t take part in any physical activities. "
Because her FOP didn’t rapidly progress at such a young age, as is the case with many FOP patients, Danzer remained mobile and able to walk and even jog until she turned 19. Because her FOP wasn’t noticeable while she was in school, she neglected 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 flare up that took away my walking ability at 19, I started to open up about it. Because it was now very clear I had a disability and it wasn’t something I could hide anymore.”
Danzer describes that flare up, which lasted nearly two years, as the worst experience she had ever had to deal with, adding, “It really broke my confidence and I contemplated a lot on all the things I lost because of FOP, mainly my independence.”
In the past five years, Danzer has started a job, renewed her social life with friends and adapted to doing things differently. Following a jaw flare-up two years ago, her ability to eat was affected, limiting her diet to mainly soft foods, such as smoothies and protein shakes.
“I still get little flares every now and then but nothing has been serious enough that I’ve lost any mobility,” she says. “FOP is so unpredictable so I just take it one day at a time and appreciate that today is a good day.” Being involved with the FOP community, fundraising 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 biotechnology companies have expressed interest and around 16 are actively developing drugs for clinical trials. At least six clinical trials are currently going on now for adults.
For pharmaceutical companies, Kaplan says, rare diseases such as FOP are challenging in their own right and are attractive to study because they reveal seminal signalling pathways that are targetable by drugs, which can also be used to treat more common conditions, such as hip and joint deterioration.
“We are just starting to enter into the era of clinical trials with small molecules that can inhibit the extra bone,” he adds. “Some of these methods to inhibit an overactive pathway will help other investigators.”
Correction 08/03/22, 12:33 p.m. ET: Corrects description of Focus On FOP website
