Practical Information for Families
Unfortunately, at the moment, no formal standard of care exists for Myofibrillar Myopathy type 13 (MFM13) with Rimmed Vacuoles. However, a standard of care has been developed and published for VCP (Valosin-containing protein) disease, thanks to the efforts of the Cure VCP advocacy group. VCP disease shares many overlapping features with MFM13, especially related to myopathic symptoms, and the supportive therapies section below is based on the guideline described. The full document can be accessed via this link.
There is currently no approved treatment to slow down or stop MFM13, so care focuses on managing symptoms. Patients should visit a multidisciplinary clinic every six months, where they can see an interdisciplinary team including a neurologist, physical therapist, occupational therapist, speech-language pathologist, respiratory therapist, and social worker. This team will help manage symptoms like muscle weakness, breathing problems, and muscle cramps. Supportive measures, such as using mechanical aids and maintaining a healthy weight to avoid obesity, can also be helpful.
Exercise
We know that MFM13 affects how muscle cells respond to mechanical stress. This means that not every type of exercise is equally safe—or helpful. No clinical studies have been done yet in MFM13, but below we summarize what we know about how exercise affects HSPB8, the protein involved in this disease.
What we know about HSPB8 and exercise
In healthy muscle, HSPB8 helps repair tiny injuries that happen when we move or train. The protein is part of a stress-response system called CASA (Chaperone-Assisted Selective Autophagy), which protects the muscle’s structure.
Research in healthy volunteers shows that:
- Gentle, low-intensity exercise does not change HSPB8 levels.
- High-intensity or eccentric exercise (where muscles lengthen under load—like downhill running or heavy lowering movements) causes micro-damage to muscle fibers.
This strongly activates CASA and temporarily uses up HSPB8, followed by a rise in HSPB8 production.
- Regular strength training over time increases the amount of HSPB8 the muscle produces.
Why this matters in MFM13
People with MFM13 produce a mutant form of HSPB8. This mutant protein has a toxic gain-of-function, meaning that higher levels can worsen the underlying problem in muscle cells.
This leads to several important conclusions:
1. High-intensity exercise can increase production of the mutant protein
Anything that strongly activates CASA—heavy, damaging, or eccentric exercise—signals the muscle to make more HSPB8. In MFM13, this includes more mutant HSPB8, which may increase stress on the muscle.
2. High mechanical strain may overload an already stressed repair system
MFM13 already affects how the muscle handles structural proteins like filamin and how efficiently CASA works.
Activities that create a lot of mechanical damage can push this system beyond its limits.
3. Low-intensity exercise is expected to be safe—and likely helpful
Gentle activity does not trigger large changes in HSPB8 and does not cause significant muscle disruption. It supports overall health, reduces fatigue, helps maintain mobility, and is widely used safely in other myofibrillar myopathies.
What to avoid
As far as we know, to protect the muscle from unnecessary strain, it is best to avoid or minimize:
- Eccentric-heavy exercises (e.g., downhill running, fast downhill hiking, heavy lowering movements)
- High-intensity interval training (HIIT)
- Maximal-effort strength training
- “No pain, no gain” workouts designed to cause muscle soreness
- Sudden jumps in training volume or intensity
These activities can activate HSPB8 production and increase damage to Z-disks—areas already fragile in MFM13.
Recommended types of exercise
To the best of our knowledge, it is safer for an MFM13 patient to perform low-to-moderate, steady, non-eccentric activity. Examples include:
1. Concentric-focused strengthening
- Resistance bands or machines
- Light weights, slow controlled movements
- Higher repetitions at low loads
- Stopping well before form breaks down or fatigue hits
2. Aerobic (endurance) activities
- Cycling (excellent because it minimizes eccentric load)
- Swimming or water exercise
- Walking on level ground
- Elliptical trainer
Consistency is key
Short, regular sessions are better than infrequent hard workouts.
The goal is supporting health, mobility, and quality of life—without stressing the muscle’s repair system.
If you live with MFM13, it is helpful to:
- Work with a physiotherapist familiar with neuromuscular disease
- Track how your body responds to different activities
- Avoid exercise that causes unusual or prolonged muscle pain
Key messages
- Exercise affects HSPB8 levels depending on intensity and type.
- In MFM13, higher HSPB8 production means more mutant protein.
- High-intensity or eccentric exercise can overload the muscle’s repair system.
- Low-intensity, steady activity is expected to be safer.
- Gentle movement, done regularly, supports overall wellbeing without activating harmful pathways.
References: (1)–(3)
1. Ulbricht A et al. Cellular Mechanotransduction Relies on Tension-Induced and Chaperone-Assisted Autophagy. Curr Biol. Published online 2013:430-435.
2. Ulbricht A et al. Induction and adaptation of chaperone-assisted selective autophagy CASA in response to resistance exercise in human skeletal muscle. Autophagy. 2015;11(3):538-546.
3. Ottensmeyer J et al. Force-induced dephosphorylation activates the cochaperone BAG3 to coordinate protein homeostasis and membrane traffic. Curr Biol. Published online 2024:4170-4183.
Respiratory Therapy
Respiratory therapy is crucial for monitoring and managing breathing function. Pulmonary function tests should be done at least once a year, measuring forced vital capacity (FVC) in both sitting and lying down positions. Timely use of chest physiotherapy, non-invasive ventilation, and devices that help with breathing in and out can be very beneficial.
Speech-Language Pathology
Assessing bulbar function, which involves the muscles used for speech and swallowing, is crucial because it is closely connected to breathing and nutritional health. Speech-language pathologists evaluate how well a person can swallow, their speaking rate, and overall clarity of speech. A swallow study, using techniques like videofluoroscopy or flexible endoscopy, can detect swallowing difficulties and guide targeted treatments.
Specific diets and supplements haven't been properly studied in individuals with MFM13. However, a lipid-enriched diet has been shown to improve survival and muscle health in mice with a similar condition, though more research is needed to confirm these effects in humans.
It's reasonable to recommend an anti-inflammatory diet. This diet should be rich in fruits and vegetables, whole grains, lean proteins, and fatty fish, while avoiding highly processed foods and products with preservatives, pesticides, and artificial ingredients. Additionally, there is some evidence that a Mediterranean diet, which is protective against dementia and cardiovascular disease, might also be beneficial for the patients.
Family monitoring
People with HSPB8 mutations who do not yet have muscle weakness, as well as family members at risk, should be regularly checked for early signs of muscle problems. This involves standard strength and functional tests conducted by a multidisciplinary team. If muscle weakness is detected, they should have regular follow-ups to monitor for any progression and consider possible interventions. These check-ups should occur every 6 to 12 months, or more frequently if the muscle weakness worsens more quickly.
