Allen Carney was an athletic kid when he was growing up in Fayetteville, Arkansas, and one with diverse pursuits: he played football and took ballet. When it came time for college, Southern Methodist University in Texas offered him a football scholarship, but thanks to an injured knee, he decided to study geology at the University of Arkansas and pursue a career in the oil industry instead. But he still had an active physical life. After graduation, he spent the first few years working as a surveyor, “carrying lots of equipment and hiking up and down hills and mountains and everything else, just feeling wonderful,” he remembered.

But in 2000, Carney, who by this time was working as an information technology director while also caring for his 35-acre horse farm, started having trouble moving one of his legs and could no longer flex his right foot. A neurologist in Fort Smith suspected muscular dystrophy and ordered a muscle biopsy, which was inconclusive. Carney began doing his own research through the Muscular Dystrophy Association (MDA), which eventually led him to an expert at the University of Rochester Medical Center in New York. There, in 2005, Carney had a genetic test that confirmed the diagnosis definitively: facioscapulohumeral muscular dystrophy. He was 55 years old.

Carney’s story, of a physically active person who doesn’t experience symptoms of the disease until middle age, might surprise some people, including those whose understanding of muscular dystrophy comes from hearing about “Jerry’s Kids,” the moniker for the children on the MDA Labor Day Telethon, which comedian Jerry Lewis hosted annually from 1966 to 2010. But the disease varies, and the term “muscular dystrophy” actually refers to a group of diseases with more than 30 known types. Some types of muscular dystrophy present in childhood, while others don’t make themselves known until the person is an adult. Some forms of the disease are severe, cause rapid muscle deterioration and affect the heart, lungs or other organs, shortening the person’s life, while other types are mild and progress slowly, with much less impact on the person’s mobility or lifespan. Different forms of the disease also target different muscle groups.

The most severe type, Duchenne muscular dystrophy, typically starts causing symptoms between the ages of 2 and 3, according to the MDA, and overwhelmingly affects boys. Duchenne is also the most common muscular dystrophy, affecting 1 in 3,500 to 5,000 male births. Myotonic dystrophy, the second most common type, affects both sexes and symptoms can start from birth to age 70. Facioscapulohumeral muscular dystrophy, the disease Carney has, is the third most common type of muscular dystrophy. It starts showing symptoms for most people in early adulthood (Carney is not typical), and both sexes can have it.

“In general, muscular dystrophies are progressive diseases that tend to cause destruction of muscle and occur over the lifetime of the individual,” said Jeffrey Statland, M.D., professor of neurology at he University of Kansas School of Medicine. “They can be due to genetic changes that leave you with an absent structural protein in your muscle. But there are also other genetic reasons — the change could cause something that's just toxic to the muscle.”

Muscular dystrophies are also inherited. Carney believes that his father had facioscapulohumeral muscular dystrophy, albeit with mild symptoms, though his dad never sought a diagnosis or even acknowledged he had a problem. Carney remembers the way his father always struggled when he had to reach above his head, and he also now realizes the real reason his dad always wore cowboy boots, which Carney and his siblings used to make fun of.

“We thought, that’s just Dad, trying to be a cowboy or something,” said Carney. “But the way those boots fit him kept him from tripping over his own feet, because the form of the boot kept his foot from dropping.” (Difficulty raising the front of the foot, a condition known as foot drop, is a common symptom of facioscapulohumeral muscular dystrophy.)

Muscular dystrophies also share this unfortunate fact: They are not curable. But over the past decade, the field has experienced rapid progress.

“There has been a real revolution in treatment for our inherited neuromuscular disorders, and muscular dystrophies are no different,” said Statland, who also is Carney’s current physician. “This is largely being driven by molecularly designed and gene-targeted therapies. And this is not one treatment, but a series of different approaches for treating genetic diseases.”

Milestones

The obvious example is the 2023 U.S. Food and Drug Administration (FDA) approval of the first gene therapy for Duchenne muscular dystrophy. Beginning in early childhood, not only is Duchenne one of the most disabling forms of the disease — many boys need a wheelchair by the age of 12 — but it also can cause heart and respiratory problems as it progresses, and patients often die in their 20s and 30s.

Administered as a single infusion, the gene therapy, delandistrogene moxeparvovec (brand name, Elevidys), developed by Sarepta Therapeutics, delivers a gene that produces microdystrophin, a shortened version of the vital protein missing in boys with Duchenne. Clinical trial results showed that Elevidys improved motor function, and ambulatory patients had modest improvements in the time it took them to walk a short distance and stand up from the floor. Safety concerns arose in the summer of 2025 after two teenagers, both unable to walk, died from liver failure after receiving Elevidys, and Sarepta put a hold on the therapy. The hold was lifted less than two weeks later for patients still able to walk, who generally do not require as high of a dose. Sarepta also is exploring the use of immunosuppressants to lower the risk of liver injury. Elevidys cannot undo muscle damage, and it is not a cure, but it remains a milestone because it is the first systematically delivered gene replacement therapy approved by the FDA for the disease.

Constantine Farmakidis, M.D., who treats patients at KU’s muscular dystrophy clinic, which is part of the MDA Care Center Network, noted also the shift that has taken place over the past decade in how neuromuscular diseases are diagnosed, through the availability of genetic testing. In the past, most diagnoses relied on muscle biopsies, which are more invasive. But now doctors often can start with genetic testing using a blood sample, Farmakidis said, so a muscle biopsy may not be necessary. And treatment options are emerging as well.

“There are some important things we can say now to patients that we couldn’t say five, 10 or 20 years ago,” said Farmakidis, also an associate professor of neurology at KU School of Medicine. “Before, we didn’t even have clinical trials because the scientific community did not understand the genetic mechanism of the disease, the pathophysiology. But now there are some investigational agents and clinical trials trying to address the molecular problem in some of these diseases. That’s something we can say to a larger proportion of patients than we could before.”

A number of these trials are happening at KU Medical Center, which has become a leading institution in neuromuscular disease research, with one of the largest clinical trial units in North America. When Mazen Dimachkie, M.D., professor of neurology at KU School of Medicine, left the University of Texas Health Science Center at Houston to come to KU and head the Neuromuscular Division in 2007, the division had 12 active studies in neuromuscular diseases, he said. Now there are upward of 70. And it’s not just the increase in number that is an achievement.

“The division has done important studies, which are good and necessary, such as randomized controlled trials — Drug A versus placebo,” Dimachkie said. “And in the last several years, our research has evolved to being able to advance into the world of gene therapies and cell therapies, including CAR T-cell (chimeric antigen receptor T-cell), NKAR (natural killer) and mRNA CAR cell therapies.”

Dimachkie is himself an internationally known researcher in myositis, a group of inflammatory diseases that make the immune system attack the muscles, and in Pompe disease, a rare muscle-weakening disease that leads to respiratory failure and early death if untreated. If you ask him to name the most important research contributions made by the Neuromuscular Division over the past decade or two, he will resist identifying any favorites. But he will confirm that KU has been part of the international study group that, in collaboration with industry, introduced a breakthrough molecularly targeted treatment that improves the course of spinal muscular atrophy, a rare genetic syndrome that weakens voluntary muscles, causes them to waste away and, when untreated, leads to premature death. And he will mention that KU was part of the research study that led to the approval of the first drug on the market for Lambert-Eaton syndrome, an ultra-rare disorder in which the immune system attacks the area where nerves and muscles connect.

KU also participated in clinical trials for all of the six new medications approved since 2017 for myasthenia gravis, an autoimmune condition that breaks down the communication between nerves and muscle, causing double vision, droopy eyelids, choking and limb and respiratory muscle weakness that is worse after activity and improves after rest. There were very few drugs for the disease before these came along, and they were usually originally drugs for rheumatoid arthritis that had significant long-term side effects, noted Mamatha Pasnoor, M.D., professor of neurology at KU School of Medicine and an expert in the disease. Some of the new drugs are monoclonal antibodies designed specifically for myasthenia gravis.

For muscular dystrophies, researchers are looking to follow suit.

Networking

After spending many years traveling from Arkansas to the Kennedy Krieger Institute, an affiliate of Johns Hopkins Medicine in Baltimore, where he also participated in a number of research studies, Carney read about KU’s Neuromuscular Division in Kansas City. He asked his Hopkins doctor about it, and she confirmed that Statland was doing research in facioscapulohumeral muscular dystrophy at KU. In 2017, realizing that an internationally recognized expert in his disease was “right up the road,” Carney decided to make the switch.

Statland was mentored by Rabi Tawil, M.D., the doctor at the University of Rochester Medical Center who definitively diagnosed Carney, and one of the world’s leading experts on facioscapulohumeral muscular dystrophy. After Statland’s fellowship in Rochester ended and he began working at KU Medical Center in 2014, he and Tawil, now retired, worked together to establish the Facioscapulohumeral Muscular Dystrophy Clinical Trial Research Network, a consortium of 35 academic medical centers across more than 10 countries. The purpose of the network, directed by Statland, is to accelerate the development of treatments. Data from the studies the network supports, in addition to biological samples, are used by companies or researchers trying to develop therapies or understand the disease. Nearly all the clinical trials that have happened over the last 10 years had data from this network, Statland said.

Along with researchers at the University of Rochester Medical Center and Virginia Commonwealth University, Statland also created the Muscular Dystrophy Clinical Research Network, which is an umbrella network for several different consortiums for different muscular dystrophies. Michaela Walker, MPH, a research project manager for Statland who helps lead these networks and coordinates clinical trials, noted that muscular dystrophies are rare diseases. The Orphan Drug Act of 1983, which sought to facilitate drug development for rare diseases, defined rare diseases as those affecting fewer than 200,000 Americans. Networks enable multiple sites to pool expertise and resources and work together to increase the number of patients needed to participate in studies.

“Most of our diseases are going to be less than 100,000,” said Walker. “That’s why we need these networks.”

Works in progress

One of those rare diseases is Limb-Girdle muscular dystrophy, which is caused by gene mutations that result in the deficiency of proteins needed for muscle function, regulation and repair. Statland is the site principal investigator at KU Medical Center on a multi-site Phase 1/2 trial testing a gene therapy for a subtype of Limb-Girdle, caused by a facioscapulohumeral muscular dystrophy gene mutation, that affects fewer than 5,000 people in the United States. People with this condition experience muscle weakness and deterioration in their arms and legs, reduced mobility and impaired heart and lung function. There is no treatment beyond managing symptoms. Administered as a one-time infusion, the experimental therapy, AB-1003, developed by AskBio Inc., is designed to “give it [the gene] back, so it essentially delivers the enzyme so that the muscle can do what it’s supposed to do,” said Statland.

KU is also participating in a clinical trial for myotonic dystrophy, a disease that, Farmakidis said, did not have any clinical trials just a few years ago.

Affecting people of any age, myotonic dystrophy is a multisystem disease that causes progressive muscle loss and weakness and may also involve the heart, eyes and respiratory and endocrine systems. Early in the course of the disease, patients sometimes also have difficulty relaxing their muscles, making it hard, for example, to let go of someone’s hand. The Phase 3 trial will test an RNA-based investigational drug known as del-desiran, produced by Avidity Biosciences, that destroys the extra-long messenger RNA caused by a damaged gene, a hallmark of the disease. The trial will measure the effectiveness of the drug by its effect on the strength of the hand and the amount of time it takes participants to release their hand grip.

Work in muscular dystrophy at KU is even happening outside of the Neuromuscular Division. Pradeep P.A. Mammen, M.D., professor of cardiovascular medicine and division chief for Advanced Heart Failure Therapeutics and Cardiac Transplantation at The University of Kansas Health System, is the principal investigator on a trial for Duchenne muscular dystrophy. The trial does not attempt to reverse the underlying cause of the disease, but to address the resulting heart problems that so often kill boys with this condition. It is the first cardiovascular gene therapy trial for Duchenne, and KU is one of just three institutions participating.

The gene therapy in this trial targets the production of a protein known as SERCA2a, which is deficient in people with cardiomyopathy related to Duchenne. The SERCA2a protein is critical for the heart to be able to contract and relax and pump blood throughout the body. Using a catheter-based system that infuses the experimental gene therapy directly into the main coronary arteries, the trial will deliver extra copies of the gene that produces the SERCA2a protein to the heart muscle cells. The goal is to increase the production of the SERCA2a protein and regulate the movement of calcium, which helps the heart pump blood properly. The initiation of this trial marks an important step forward in addressing the cardiac complications that ultimately affect nearly all patients with Duchenne muscular dystrophy.

“This is a very big deal, for the Duchenne muscular dystrophy community and for rare diseases,” said Mammen.

Led by Statland, KU is also participating in the first trial of a drug designed specifically to go into muscle and target the molecular cause of facioscapulohumeral muscular dystrophy, which affects one in 20,000 people worldwide, according to the MDA. Facioscapulohumeral muscular dystrophy weakens and shrinks muscles in the face, shoulders, upper arms and lower legs. It also can impair other muscles in the body. The drug, dubbed del-brax by manufacturer Avidity Biosciences, decreases the expression of a gene called DUX4 that is usually inactive in healthy people but makes toxic proteins in the muscles of people with facioscapulohumeral muscular dystrophy. Early results of the Phase 1/2 trial showed that del-brax (short for delpacibart braxlosiran) lowered levels of DUX4-regulated genes in the trial participants by an average of more than 50% and levels of circulating DUX4-related proteins by 35%. Moreover, participants in this early trial who received del-brax saw some improvements in muscle strength and function compared with those who received the placebo. The drug also reduced levels of creatine kinase, which is an indicator of muscle damage. The trial is now enrolling more participants, including at KU, for Phase 3.

“We're really excited about these gene-targeted therapies, and there’s also a trial going on right now for muscle regenerative therapy and a repurposed drug that's in a Phase 1/2 study,” said Statland. “That's what you want to see for drug development for a rare disease.”

Hope

The repurposed drug that Statland referred to is Clenbuterol, a powerful prescription medication approved in the European Union to treat chronic obstructive pulmonary disorder. The FDA has not approved it for any kind of use in humans. But it has shown potential in preclinical studies to inhibit DUX4 in muscle sample cells from facioscapulohumeral muscular dystrophy patients, and it promotes muscle growth. KU is one of three sites conducting the Phase 1/2 study to begin assessing the safety of Clenbuterol, at three dose levels.

It doesn’t take a full-blown cure to make a difference for a patient, noted Statland.

Allen Carney could be one of those patients. He has participated in numerous studies over the years that do things like tracking the progression of the disease, but this is his first clinical trial testing a medication. And at age 75, it was the only trial he was eligible for. Meanwhile, his younger sister has been diagnosed with facioscapulohumeral muscular dystrophy, and his older brother has many of the same symptoms, though he has not been diagnosed. Carney says that one of the happiest days of his life was when his daughter called and told him that she had been tested for the disease and did not have it.

Today, Carney wears orthotics in both shoes to keep from tripping over his feet. He no longer can raise his arms very high, and the disease is affecting his upper legs more than it used to. He says he’s lucky that his facioscapulohumeral muscular dystrophy has not affected his face much.

“I would love to be able stop the progression of this muscle disease,” said Carney. “That's one of my hopes. The other hope is that if that doesn't occur, that they will learn something from the trial that will help others in the future.”