Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder that progressively weakens skeletal muscles, particularly those in the face, shoulders, and upper arms. While no cure currently exists, ongoing research into innovative treatments offers hope, and many effective approaches are already available to help people with FSHD manage symptoms, maintain function, and improve their quality of life.

Treatment Goals and Current Approaches for FSHD

When someone receives a diagnosis of facioscapulohumeral muscular dystrophy, the immediate question often becomes: what can be done? The answer is more hopeful than many realize. While medical science has not yet developed a treatment that can reverse or halt FSHD completely, the focus of care is on managing symptoms, slowing disease progression where possible, preserving muscle function, and maintaining the best possible quality of life^[9].

Treatment strategies for FSHD must be tailored to each individual, as the disease manifests very differently from person to person. Some people experience only mild symptoms that appear later in life, while others face more significant challenges beginning in childhood. The variability means that what helps one person may not be appropriate for another^[19]. Healthcare providers consider factors such as disease stage, which muscle groups are affected, the severity of weakness, and how symptoms impact daily activities.

It’s important to understand that “treatment” and “cure” are different concepts. A cure would eliminate the disease entirely and restore complete health. A treatment, on the other hand, helps manage symptoms and improve function even when the underlying condition remains. Many chronic diseases—such as diabetes—cannot be cured but can be managed very effectively for decades with appropriate treatment^[9].

Standard care for FSHD draws on medical guidelines developed by specialists in neuromuscular diseases. At the same time, researchers worldwide are conducting clinical trials—carefully controlled studies that test experimental drugs and therapies. These trials represent the cutting edge of FSHD research and offer paths toward future treatments. Some of these experimental approaches have already shown promising early results^[15].

Standard Treatment Options for FSHD

Currently, no medications have been specifically approved by regulatory agencies like the U.S. Food and Drug Administration solely for treating FSHD. However, doctors use several established treatments to address specific symptoms and complications that arise from this condition^[8].

Pain Management

Pain is one of the most common and challenging symptoms in FSHD. Between 50 and 80 percent of people with this condition experience chronic pain^[12][13]. The pain can have many sources: muscles working harder to compensate for weakness, joints stressed by abnormal movement patterns, or direct muscle damage from the disease process.

Healthcare providers often start with nonsteroidal anti-inflammatory drugs (NSAIDs), which are the same medications many people take for arthritis or other inflammatory conditions. These drugs reduce inflammation and provide pain relief. For chronic pain that doesn’t respond to NSAIDs, doctors may prescribe antidepressants or antiepileptic medications. While these drugs were originally developed for depression or seizures, they have proven effective for certain types of chronic pain by changing how the nervous system processes pain signals^[8].

Pain management specialists can work with FSHD patients to develop comprehensive strategies. Non-drug approaches such as cognitive behavioral therapy and mindfulness techniques can be as effective as medication for some people. The key is finding an individualized approach, as pain is highly subjective and what works varies greatly from person to person^[20].

Physical Therapy and Rehabilitation

Physical therapy plays a central role in FSHD management. Unlike many rehabilitation programs that focus on recovery, physical therapy for FSHD aims to maintain current function, support fitness, and improve or preserve balance. Because FSHD is a progressive condition, the realistic goal is often to slow decline rather than to regain lost muscle strength^[20].

Finding a physical therapist with experience in neuromuscular or degenerative conditions is important. These specialists understand that standard strengthening exercises designed for recovery may not be appropriate. Instead, they work with patients to develop safe exercise programs that won’t cause overwork damage to already weakened muscles. Activity and movement are encouraged, as complete inactivity can actually worsen muscle disease^[12].

Occupational Therapy

Occupational therapists help people with FSHD maintain independence in daily activities. They can suggest adaptive equipment, teach energy conservation techniques, and recommend modifications to home or work environments. These practical interventions help people continue performing important tasks despite progressive weakness^[12].

Supportive Devices and Equipment

Various devices can compensate for muscle weakness and improve function. Orthoses—supportive devices such as braces—are commonly used. Back supports, corsets, girdles, and specialized bras can help compensate for weakening muscles in the upper and lower back. These supports are often recommended by physical therapists^[8].

Lower leg braces, known as ankle-foot orthoses (AFOs), are particularly helpful for people who develop foot drop—the inability to lift the front part of the foot. This condition makes walking difficult and increases the risk of tripping and falling. AFOs can be purchased as off-the-shelf models or custom-made to fit individual needs^[8].

Surgical Interventions

In some cases, surgery can improve function for people with FSHD. The most common surgical procedure involves stabilizing the shoulder blades by attaching them to the ribs. This procedure is called scapular fixation. In FSHD, weak shoulder muscles allow the shoulder blades to move abnormally, creating the characteristic “winging” appearance and making it difficult to raise the arms^[8].

During scapular fixation surgery, the shoulder blades are secured to the ribs so they cannot slide around. While this actually decreases the arm’s range of motion—because the shoulder blade can no longer rotate normally—many patients gain better arm function because the arm has a stable leverage point. This can make it easier to perform daily tasks. However, it’s crucial to seek a surgeon who fully understands FSHD and has specific experience with this procedure^[8].

Managing Complications

Because FSHD can affect various body systems, regular monitoring for complications is important. Some people develop abnormalities in the blood vessels at the back of the eye, a condition called retinal telangiectasia, or more rarely, Coats disease. Regular eye examinations can detect these problems early^[12][13].

High-frequency hearing loss occurs in about 50 percent of people with FSHD, though it often doesn’t cause noticeable symptoms and may only be discovered during medical testing^[5]. Hearing tests can identify this issue if it develops.

Rarely, FSHD affects the heart muscle or the muscles needed for breathing. For this reason, some doctors recommend periodic cardiac testing and pulmonary function tests to monitor heart and lung health. If respiratory muscle weakness develops, devices such as BiPAP (bilevel positive airway pressure) can help support breathing^[12].

Speech Therapy

When facial muscle weakness affects the ability to speak clearly or swallow safely, speech therapists can provide exercises and strategies to improve communication and eating^[12].

Experimental Treatments in Clinical Trials

The landscape of FSHD treatment is rapidly evolving as scientists develop a clearer understanding of what causes the disease at a molecular level. This knowledge has opened the door to targeted therapies designed to address the root cause of FSHD rather than just managing symptoms. Multiple experimental drugs are now being tested in clinical trials at various stages^[15].

Understanding the Disease Mechanism

To understand how new experimental treatments work, it helps to know the basic mechanism of FSHD. The disease results from inappropriate expression of a gene called DUX4. Normally, the DUX4 gene is active only in very early embryonic development and is turned off in nearly all adult tissues. In people with FSHD, genetic changes cause DUX4 to become active in muscle cells throughout life. The DUX4 protein is toxic to muscle cells, causing them to die and leading to progressive muscle weakness and atrophy^[3][5].

There are two types of FSHD based on the genetic cause. FSHD1, which accounts for about 95 percent of cases, occurs when a region of DNA called D4Z4 on chromosome 4 becomes abnormally shortened, reducing the number of repeat segments from the normal 11 to 100 down to between 1 and 10. This contraction leads to reduced methylation—chemical modifications that normally keep genes turned off—allowing DUX4 to become active^[5][6].

FSHD2 accounts for the remaining 5 percent of cases and usually results from mutations in a different gene called SMCHD1. This gene normally produces a protein that helps keep the D4Z4 region highly methylated and DUX4 turned off. When SMCHD1 is mutated, methylation decreases, and DUX4 becomes inappropriately active—just as in FSHD1, but through a different route^[5][7].

Targeting DUX4 with Antisense Therapy

One promising approach being explored uses antisense oligonucleotides (AOs). These are short pieces of synthetic genetic material designed to bind to specific RNA molecules—the messages that carry genetic instructions from DNA to the protein-making machinery of cells. When an antisense oligonucleotide binds to DUX4 messenger RNA (mRNA), it can prevent the toxic DUX4 protein from being made^[14].

Research has shown that antisense oligonucleotides can successfully reduce expression of DUX4 and related downstream molecules such as PITX1 (paired-like homeodomain transcription factor 1), which is activated by DUX4 and contributes to muscle damage. Laboratory studies have demonstrated successful suppression of these targets in animal models, raising hopes that this approach could be translated into human treatments^[14].

Delpacibart Braxlosiran (Del-Brax): A Phase 1/2 Trial

One of the most exciting recent developments in FSHD research involves a drug called delpacibart braxlosiran, shortened to “del-brax.” This experimental medication represents the first molecularly designed, gene-targeted treatment specifically created to go into muscle tissue and knock down the DUX4 protein^[15].

Del-brax, developed by Avidity Biosciences, is being tested in a multi-site clinical trial called FORTITUDE. This is a Phase 1/2 trial, meaning it is designed both to assess safety (Phase 1) and to gather preliminary evidence about whether the drug works (Phase 2). The University of Kansas Medical Center is among the sites conducting this trial^[15].

Preliminary results from the FORTITUDE trial have been encouraging. After four months of treatment, participants receiving del-brax showed an average reduction of more than 50 percent in levels of DUX4 expression in their muscles. Levels of DUX4-related proteins decreased by 25 percent. These reductions represent the first proof of principle that directly targeting DUX4 in muscle can be achieved in humans^[15].

The trial represents an important milestone because it demonstrates that the therapeutic strategy—delivering a treatment directly to muscle to silence the disease-causing gene—is feasible. While these are early results and do not yet show whether patients experience functional improvements, they provide crucial evidence that the approach has biological activity^[15].

Losmapimod: Targeting Inflammation

Another experimental drug being studied for FSHD is losmapimod. This medication works differently from antisense approaches. Losmapimod is a small molecule that inhibits an enzyme called p38 mitogen-activated protein kinase (p38 MAPK). This enzyme plays a role in inflammatory pathways and cellular stress responses. The theory is that blocking this enzyme might reduce the downstream muscle damage caused by DUX4 activation^[10].

Losmapimod is currently being tested in a Phase 1 trial called ReDUX4. Phase 1 trials focus primarily on safety—determining whether the drug is well-tolerated at various doses and identifying any side effects. Early results from this trial have been described as promising, though detailed data have not yet been fully published^[10].

Albuterol: Repurposing an Existing Drug

Sometimes, drugs developed for other conditions prove useful for FSHD. Albuterol (also known as salbutamol) is a medication commonly used to treat asthma by relaxing airway muscles. Researchers discovered that this drug might also increase muscle mass in FSHD patients^[10][12].

Several clinical trials have tested oral albuterol in people with FSHD. Results have been mixed but somewhat encouraging. Three out of four clinical trials found statistically significant improvements in muscle strength, particularly in the elbow flexors (the muscles that bend the arm at the elbow). However, while albuterol appeared to increase muscle mass, it did not consistently improve muscle strength across all muscle groups tested^[10].

This distinction is important: having more muscle tissue doesn’t always translate into better function if the muscle quality is compromised by the disease process. Nevertheless, some doctors do prescribe albuterol to FSHD patients, though it is not specifically approved for this use^[12].

Antioxidant Combinations

Because oxidative stress—damage caused by unstable molecules called free radicals—may play a role in muscle damage in FSHD, researchers have tested combinations of antioxidants. One clinical trial evaluated a combination of vitamin C, vitamin E, zinc gluconate, and selenomethionine (a form of the mineral selenium)^[10].

The study found significant improvement in two measures: maximal voluntary contraction (the maximum force a muscle can generate) and endurance limit time (how long a muscle can sustain effort) of the quadriceps muscle (the large muscle on the front of the thigh). These results suggest that reducing oxidative stress might have some benefit, though more research is needed to confirm these findings and understand their practical significance^[10].

Drugs That Haven’t Worked

It’s also important to understand which experimental approaches have been tried but did not prove effective. Diltiazem, a calcium channel blocker normally used to treat high blood pressure and heart conditions, was tested in FSHD but showed no improvement in muscle function, strength, or mass^[10].

Similarly, MYO-029, an experimental drug designed to block myostatin (a protein that limits muscle growth), was also tested. Despite the theoretical rationale that blocking myostatin might allow muscles to grow larger and stronger, MYO-029 demonstrated no benefit in FSHD patients^[10].

These negative results are still valuable. They help researchers understand which pathways are or are not promising targets for therapy and guide the direction of future research.

Hormone Combination Therapy

A recent Phase 1/2 clinical trial tested a combination of recombinant human growth hormone (rhGH) and testosterone in adult men with FSHD. The rationale was that growth hormone helps cells grow and regenerate, while testosterone supports muscle building. Together, they might help counteract muscle loss^[11].

Twenty men with FSHD who could still walk independently participated. For six months, they gave themselves daily injections of growth hormone and received testosterone shots every two weeks. The results were encouraging: participants gained an average of about 4.5 pounds of lean muscle and lost around 3 pounds of fat. In a standard walking test (the six-minute walk test), they improved by roughly 37 meters (120 feet)—enough to make everyday activities noticeably easier. Muscle strength increased by about 3 percent, and participants reported feeling better overall^[11].

Importantly, many of these gains persisted even three months after treatment stopped. The treatment was well-tolerated, with 19 of 20 participants completing the program and experiencing only mild side effects, mostly soreness at injection sites. The lead researcher, Chad Heatwole, MD, noted that this represents “the first treatment to not only slow this disease, but help patients regain function”^[11].

This success has prompted plans for larger, multi-center randomized controlled trials to confirm the benefits. The researchers also plan to include women with FSHD and fine-tune dosing. If future studies support these findings, the hormone combination could become an important treatment option^[11].

How Clinical Trial Phases Work

Understanding clinical trial phases helps make sense of where different experimental treatments stand in the development process. Phase 1 trials focus primarily on safety. They involve small numbers of participants and aim to determine whether a treatment is safe, identify appropriate doses, and watch for side effects^[10].

Phase 2 trials expand to larger groups and focus on whether the treatment actually works—does it have the intended biological effect? Does it improve symptoms or function? These trials provide the first real evidence of efficacy^[10].

Phase 3 trials are large studies that compare the new treatment to current standard care or placebo. These trials provide the definitive evidence needed for regulatory approval. Phase 4 trials occur after a drug is approved and monitor its long-term safety and effectiveness in broader populations^[10].

Where Trials Are Conducted

FSHD clinical trials are being conducted at specialized neuromuscular centers around the world, including locations in the United States, Europe, and other regions. Major research institutions and academic medical centers often serve as trial sites. Organizations like the FSHD Society maintain clinical trial networks to connect eligible patients with ongoing studies^[9].

Most common treatment methods

• Pain management approaches
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce inflammation and provide pain relief
  • Antidepressants or antiepileptic medications for chronic pain by modifying nervous system pain processing
  • Cognitive behavioral therapy and mindfulness techniques as non-drug alternatives
  • Individualized pain management plans developed with specialists
• Physical and occupational therapy
  • Physical therapy programs designed to maintain function rather than promote recovery
  • Safe exercise programs that avoid overwork damage to weakened muscles
  • Balance and fitness support from therapists experienced in neuromuscular conditions
  • Occupational therapy to maintain independence in daily activities
  • Energy conservation techniques and adaptive equipment recommendations
• Orthotic devices and supports
  • Ankle-foot orthoses (AFOs) to compensate for foot drop and prevent falls
  • Back supports, corsets, girdles, and specialized bras for trunk weakness
  • Custom-made or off-the-shelf braces recommended by physical therapists
• Surgical interventions
  • Scapular fixation surgery to stabilize shoulder blades and improve arm leverage
  • Procedures performed by surgeons with specific FSHD experience
• Experimental antisense therapies
  • Delpacibart braxlosiran (del-brax) targeting DUX4 messenger RNA in the FORTITUDE Phase 1/2 trial
  • Antisense oligonucleotides designed to knock down toxic DUX4 protein production
  • Approaches targeting downstream molecules like PITX1
• Small molecule drugs
  • Losmapimod inhibiting p38 MAPK enzyme in the ReDUX4 Phase 1 trial
  • Albuterol to potentially increase muscle mass (tested in multiple trials with mixed results)
• Hormone therapy combinations
  • Recombinant human growth hormone plus testosterone showing improved muscle mass, strength, and walking distance in Phase 1/2 trials
  • Daily growth hormone injections combined with biweekly testosterone injections
• Antioxidant supplementation
  • Combinations of vitamin C, vitamin E, zinc gluconate, and selenomethionine showing improvement in quadriceps muscle contraction and endurance
• Supportive care
  • Speech therapy for facial weakness affecting speaking or swallowing
  • Regular monitoring for eye complications like retinal telangiectasia
  • Hearing tests for high-frequency hearing loss
  • Cardiac and pulmonary function monitoring
  • BiPAP devices for respiratory muscle weakness