Effort Aims to Improve Life for Patients With a Rare Disease

Fibrodysplasia ossificans progressiva (FOP), also known as Münchmeyer disease, is an extremely rare connective tissue disease which causes fibrous tissue—including muscles, tendons and ligaments—to turn to bone. FOP impacts an estimated 4,000 people worldwide.

A local team guided by Dr. Zvi Grunwald—Jefferson’s chair of anesthesiology—and Dr. Fred Kaplan, from Penn Medicine, works with the International Clinical Council on Fibrodysplasia Ossificans Progressiva (ICCFOP) to push the boundaries of understanding and treating this rare disease.

Their efforts have turned Philadelphia into a hub of FOP knowledge, with Drs. Grunwald and Kaplan at the helm, traversing the globe to share their expertise into what’s been deemed “a catastrophic sabotage of the body’s muscular skeletal system.”

“At Jefferson, we created a Center of Excellence for the perioperative care of patients with FOP, and the collaboration with Penn turned Philadelphia into a mega center converging best clinical practices, innovation and emerging therapeutic solutions to benefit these patients,” says Dr. Grunwald, who serves as executive director of the Jefferson Israel Center and The James D. Wentzler Professor and Emeritus Chair of Anesthesiology.

“The motto at Jefferson is, ‘We improve lives.’ Well, we’ve taken that one step further: we improve life and living for FOP patients,” Dr. Grunwald adds. “This remains an unfolding story, and we have a global mission to go.”

Dr. Kaplan and colleagues discovered the gene that causes FOP in 2006.

Currently the Isaac and Rose Nassau Professor of Orthopaedic Molecular Medicine in Orthopaedic Surgery, Dr. Kaplan concurs with Dr. Grunwald’s sentiments, noting that the “absolutely wonderful” cross-institutional cooperation has enabled the effort to “start moving from the backwaters of a rare disease toward a watershed of medicine.”

“In a sense, we’re caught between the past and future,” says Dr. Kaplan, who first teamed up with Dr. Grunwald many years ago while researching ways to safely anesthetize FOP patients for dental work despite their jaws being fused. “We are getting to the point where the obstacles from the past aren’t obstacles, but they are the past. This has been an absolutely wonderful collaboration.”

Something as simple as dental surgery can be a life-threatening prospect for FOP patients, lending a stark level of importance to these efforts. It’s all about making medical care safer for patients who are extremely sensitive to minor injuries and even immunizations, which is why medical professionals advise against COVID-19 vaccinations for FOP patients.

In addition to these global efforts, cross-disciplinary projects at the University have already made surgical options more accessible to patients, as well as honing in on innovative ways to help surpass hurdles that FOP brings to their day-to-day lives.

Specifically, Michelle Ho, a Sidney Kimmel Medical College student—with the help of the Health Design Lab—has created 3D prints of FOP patients’ chest cavities which assist both the medical team and the patients to see what challenges inherent in performing surgery.

Meanwhile, industrial design and occupational therapy faculty and students undertook a graduate project to design devices for use by people with FOP, including a device for reaching items and to help with feeding or showering independently. Eric Schneider and Tod Corlett, respectively the industrial design program’s professor and director, say these efforts will continue, with Dr. Grunwald deeming it a pathway to an international collaboration with design students in Israel.

Dr. Grunwald traces the 3D printing effort back to when he was treating a 26-year-old FOP patient who needed surgery, but was unable to open his mouth, which made surgical options eminently risky. He turned to medical student Michelle Ho with a question.

“I wished I could have a build of the patient’s thorax to determine the impact of the disease of the respiratory system and the risk surgery would present,” he says. “I asked Michelle if she could do a 3D printing of his thorax, and she could. It showed muscles that had turned to bone and significant skeletal derangement. The risk was too high, so there could be no surgery.”

A 3D model of a 27-year-old FOP patient showed a more favorable impact of the disease and the patient underwent a successful surgery while she was cared for by a multi-disciplinary team.

Ho notes that the effort continued, creating more models for FOP patients potentially undergoing surgical intervention. She explains that she used CT scans to create 3D models for a multi-disciplinary care team from across the hospital. In short, it helps everybody know what they’re up against.

“We are lucky at Jefferson that we have the 3D lab to create complicated models,” Ho says. “With FOP patients, heterotopic ossification can form in areas where there is normally not bone. We use a combination of image post-processing and CAD software for that, to create these models. It helps with patient education. It’s more intuitive for them to see it in 3D. It also helps clinicians pre-plan surgeries.”

Ho, who hopes to become a radiologist, says working with the Health Design Lab has helped her understand the future of her field, and the role it can play as healthcare evolves.

“It’s been incredible,” says Ho, currently on her clinical rotation. “I’m so grateful to have had the opportunity to be part of the patient visits when the 3D models are used, and to have had the chance to interact with the patients and everyone involved in their care.” 

Schneider notes that the project involving the industrial design and occupational therapy programs in East Falls was sparked when Dr. Grunwald approached them seeking a collaboration. Dr. Grunwald expanded the Jefferson moto and coined it “The WILL Project,” which is short for “We Improve Life and Living of FOP patients.”

“We learned that FOP patients need to use assisted devices, but nothing is designed well for them. The idea of doing this dovetailed nicely with our program’s long-standing relationship with occupational therapy,” says Schneider, pointing to an OT doctorate program which embeds two or three students within industrial design for two semesters. “It seemed like a perfect opportunity as it’s all about activities in daily living.”

In November 2019, Schneider and several students went to Florida for the International FOP Association family gathering, where they met with families and patients.

“We looked at the things that they were forced by necessity to make for themselves,” he recalls.

Corlett says that from a design perspective, students working on problems with very extreme cases helps them understand applications of a universal nature. Meshing with an occupational-therapy mindset “tends to be very productive,” he says.

“Very little had been done for them with customization,” says Corlett of assistive devices. “This project is about working with the people with FOP, rather than for them. It’s a true collaboration. If we can restore even small independence, it’s meaningful. It opens up possibilities and lessens their isolation.”

Three of the four projects which were worked upon by students last year—reaching devices/grabbers, an aquarium-pump style device for feeding and a modular system on a wheelchair arm—will be picked up by students this year.

“We’re developing ideas and want to see this stuff taken to the manufacture level,” he says. “There is clearly a need for this. With many design programs, the projects stop when students graduate or move on. This work is important enough to carry forward.”

The commitment comes as welcomed news to Dr. Grunwald, who has traveled to places including Sweden, South Africa, Israel, and Brazil with Dr. Kaplan to advance their FOP work.

With future clinical trials, they hope to discover new medicines which specifically target the molecular defect which causes FOP. It’s why the duo helped establish the ICCFOP five years ago, and it’s why each is grateful that they’re based in Philadelphia where they can work closely together, despite being at different institutions.

“What we want to do is maintain momentum,” Dr. Grunwald says. “Surgery for FOP patients is extremely rare because of the high risks involved. At Jefferson we cared for more than 100 patients with successful anesthesia and perioperative course.  We had FOP patients coming in from five different continents to an institute in Jefferson with global distinction. We’re on the map.”