CU joins trial network taking aim at rare disease

November 12th, 2020

The University of Colorado is one of four sites recently named to join a research consortium dedicated to finding treatments for a rare, debilitating neuromuscular disease called facioscapulohumeral muscular dystrophy, or FSHD.

With the August 11 announcement, CU becomes one of 15 institutions in the United States and Europe comprising the Facioscapulohumeral Muscular Dystrophy (FSHD) Clinical Trial Research Network (CTRN). The network’s target, FSHD, is a genetic disease that attacks and progressively weakens the muscles of the face, shoulders, upper arms and legs.

The FSHD Society, an advocacy group founded nearly 30 years ago by patients with the disease, provided $300,000 to fund the CTRN expansion, which also includes the University of Florida, University of Texas Southwestern Medical Center and Stanford University School of Medicine. The CTRN aims to pool the strengths of institutions with expertise in neuromuscular disease in the hopes of finding a medical therapy for facioscapulohumeral muscular dystrophy. As yet there is none.

selfie of Justin and Amanda in the mountains, Jeff suffers from FSHD.
Justin and wife Amanda hope the University of Colorado’s inclusion in the FSHD Clinical Trials Research Network (CTRN) helps produce a therapy for the disease. Photo courtesy of Justin Hill.

A strategic approach to FSHD

The CTRN improves the chances of getting there, said Brianna Blume, manager of the Neuromuscular Research Development Program at CU. The network already runs the ReSolve trial, which aims to follow 180 to 220 FSHD patients for 18 to 24 months. As part of the CTRN, CU will be involved in a new trial, Motor Outcomes to Validate Evaluations in FSHD, or MOVE FSHD.

The overall goal of the studies: discover the best ways to measure how the arms, shoulders, hands and legs of FSHD patients function, and how their muscles change as the disease progresses.

“The point of participating in the network is to establish how we measure patients and how we create trials that accurately capture whether a drug is working or not,” she said. In turn, drug companies can use the findings of ReSolve and MOVE FSHD to design and tailor their drug trials, Blume added.

The trials and the CTRN framework, she said, will enable companies “to test their drugs against the patient population that we have already defined for them,” she said.

Ready to roll

profile shot of Dr. Matthew Wicklund
Dr. Matthew Wicklund, director of the Neuromuscular Section of the UCHealth Neurosciences Center, says FSHD patients in Colorado and the Rocky Mountain region will benefit from CU joining the CTRN. Photo courtesy of Matthew Wicklund.

The 15-center network offers drug companies a “plug-and-play” model for launching their trials, added Dr. Matthew Wicklund, a professor in the Department of Neurology at the CU School of Medicine. Wicklund also directs the Neuromuscular Section of the UCHealth Neurosciences Clinic on the Anschutz Medical Campus.

“The CTRN is like a factory built with multiple assembly lines,” he said. “You decide on what product you want to make.”

Blume said the CTRN also minimizes efforts wasted when several research centers independently work on similar projects.

“We’re all on the same page and have a say if a measure isn’t working and we’re exhausting our patients without having sufficient data,” Blume said.

In addition, the CTRN centralizes Institutional Review Board approval and regulatory oversight for trials, Blume said, and creates a far deeper pool of patients for trials than any one institution could hope to find.

Regional benefit for FSHD patients

The CTRN expansion is good news for FSHD patients in Colorado, Wicklund said. It means that a greater number in the 11-state region that CU and UCHealth University of Colorado Hospital serve will have easier access to clinical trials and a team of researchers with long-running expertise in genetic muscle disease. Prior to the expansion, the closest options in the CTRN were the University of Utah or the University of Kansas Medical Center.

“As the largest metropolitan area between St. Louis and the West Coast, we should be involved,” Wicklund said.

Blume noted that the Neuromuscular Program closely follows around 50 FSHD patients. Ten have already expressed interest in joining the research effort. In addition, the lab of Dr. Sujatha Jagannathan on the Anschutz Medical Campus, in CU’s Department of Biochemistry and Molecular Genetics, focuses its research almost exclusively on the gene responsible for FSHD.

The genetic link; signs and symptoms

Wicklund hopes CU’s inclusion in the CTRN helps to raise the profile of a disease that hasn’t gotten much attention – it affects about 1 in 8,000 individuals – but can devastate the lives of those who have it. The origins of FSHD are complex (the FSHD Society has a detailed explanation here), but the vast majority of cases spring from a mutation in the DUX4 gene that causes muscle death.

The DUX4 gene prevents unrestrained muscle growth as youngsters develop, but in people with FSHD, it becomes “disinhibited,” Wicklund explained, and muscles wither. The disease produces a host of other symptoms, including chronic fatigue, pain, and weakness.

“We need the [DUX4] gene early, but it must also be turned off early,” he said. “The ‘holy grail’ is a therapy that would turn DUX4 back off. That would theoretically turn off progression of the disease.” A gene-based therapy could be the answer, he added, “but we’re not quite there yet with this disorder.”

In Colorado, some 400 to 600 people with FSHD would stand to benefit from a therapy, said Beth Johnston, chief community development officer for the FSHD Society. But the total number in the state and internationally is probably higher, she added, because the disease produces warning signs like muscle weakness, frequent falls and face drooping that may go undiagnosed.

FSHD: A debilitating disease

Johnston sees FSHD up close every day. Her husband Jeff, now 50, began experiencing symptoms in his mid-20s that were odd for a guy who golfed three times a week, loved sports and was in good enough shape to complete the Triple Bypass Bicycle Ride over three Colorado mountain passes. In his mid-20s, though, he began tripping for no apparent reason. His knees buckled at times, his hands weakened and he lost feeling in his fingers.

As time passed, “he had more and more trouble walking, climbing stairs and lifting things over his head,” Beth said. Jeff eventually received his FSHD diagnosis at CU. He continues to work as an economist, but he now needs a scooter to get around.

Many FSHD patients and their loved ones face the same or similar difficult situations, Beth said.

“The biggest impact is watching patients progress in the disease and lose their independence and lose the things they love to do,” she said.

communication officer of FSHD society with her two teenage daughters and husband.
Beth Johnston (third from left) with husband Jeff and daughters Samantha and Nicole. Beth is chief community development officer for the FSHD Society, which funded the inclusion of CU and three other centers in the CTRN.

Unpredictable effects for affected individuals

The disease progresses unpredictably, another source of stress. Justin Hill, 35, of Highlands Ranch can attest to that. Hill, an electronics engineer at Lockheed Martin, works on the Orion spacecraft, designed one day to carry humans into deep space. No easy task, but Hill faces his own daunting challenge here on Earth.

About eight years ago, he said, he noticed that his regular workouts weren’t building muscle mass the way he expected. He hired a personal trainer, but that didn’t help. He talked to his primary care physician, who didn’t give much of an answer to the puzzling problem.

A couple of years later, the problem worsened. “I was not only not making any progress in the gym, I was going backward in terms of what I could do,” Hill said. “At that point, I was kind of freaking out.”

His PCP finally referred him to Dr. Heidi Ray, a CU-trained neurologist at Kaiser Permanente who looked at Hill’s physique and immediately suspected FSHD. She performed an electromyogram to measure electrical activity in the muscles and confirmed the FSHD diagnosis with a genetic test.

“I’d never heard of it,” Hill said. “At first I was relieved that I wasn’t just crazy and that I could put a pin in it.” But then the uncertainty of what lay ahead sunk in.

“The first couple of months after the diagnosis were pretty devastating,” Hill said. “It certainly changed my outlook on what my life was going to look like.”

Physical and mental battles against the disease

The diagnosis had profound emotional fallout. Realizing that he is a genetic carrier for FSHD, Hill and his wife Amanda, a research administrator with the CU School of Medicine and director of the Colorado chapter of the FSHD Society, decided against having children.

“The decision was for the very reason that I don’t want to pass it on,” Hill said.

Justin, who suffers from FSHD, on a boat of the California coast.
Justin Hill enjoys time on the water off the coast of Santa Cruz, California. Justin was diagnosed several years ago with facioscapulohumeral muscular dystrophy (FSHD), a genetic disease that attacks the muscles. Photo courtesy of Justin Hill.

Several years after his diagnosis, Hill continues to work full-time, grateful that the disease has thus far not affected his legs. Through trial and error, he’s found treatments that alleviate his chronic soreness and stiffness and fatigue. These include acupuncture, massages, cold laser therapy, and infrared sauna. He acknowledged the benefits may be mental, but believes the treatments have helped to relieve his symptoms.

Hill does not minimize what FSHD has taken from him. Born and raised in the Black Hills of South Dakota, he brought a love of camping, hiking, backpacking and climbing to Colorado. His weakened arms have made rock climbing a thing of the past and he struggles to walk at high altitudes. Everyday life presents challenges he never imagined. Lifting a watermelon out of a grocery store bin is too difficult. When he tried to take down Christmas lights from an overhead shelf last year, he found he couldn’t do it.

“Those realizations are hard to take,” Hill said. “That’s when you really feel like [the disease] has made progress.”

The mystery of where his life is headed compounds the physical deficits he faces. While he says fatigue bothers him the most, he’s also nagged by worries that he will lose his ability to walk.

“I was an energetic go-getter,” he said. “That bothers me a lot. The mental battle is just as hard, if not harder, than the fatigue.”

Hope for a brighter future

Still, he’s buoyed by the support of the FSHD Society and the prospect of new research and the possibility of joining clinical trials close to home that aim to stop or slow the progression of his disease.

“It’s going to be really nice for us to be able to have access to a local facility for trials,” Hill said. “Research will be a huge booster in keeping the community involved.”

The inclusion of CU in the CTRN once “seemed beyond reach,” Beth Johnston added. “People who wanted to participate in trials had to travel, and that meant they weren’t in the mix. We’ve now given people hope.”

The CTRN promises to benefit both patients and providers, Wicklund added.

“It allows patients to participate in creating the metrics that will define the future treatments of their disorder,” he said. “They will be guiding where we go in terms of therapies. For a patient, FSHD may be a rare disease, but it’s your disease.”

For more information on the CTRN, contact Jacob Bockhorst, administrative assistant for the Neuromuscular Section of the CU Department of Neurology, at 303-724-2188 or jacob.bockhorst@cuanschutz.edu.

About the author

Tyler Smith has been a health care writer, with a focus on hospitals, since 1996. He served as a writer and editor for the Marketing and Communications team at University of Colorado Hospital and UCHealth from 2007 to 2017. More recently, he has reported for and contributed stories to the University of Colorado School of Medicine, the Colorado School of Public Health and the Colorado Bioscience Association.