Frequently Asked Questions

Calpainopathy is the most common form of limb-girdle muscular dystrophy, representing an estimated 20% of all LGMD cases. However, LGMD2A/R1 and LGMDD4 are still categorized as rare diseases; scientists estimate that they affect about 1-5 in every 100,000 people.

Patients with calpainopathy typically have normal early motor milestones, but signs of muscle deterioration can be detected by elevated creatine kinase (CK) levels in the blood.

Early signs include a “waddling” gait, walking on tiptoes, scapular winging (shoulder blades protrude from the back), and/or difficulty climbing stairs. Some patients also report fatigue or muscle pain as early symptoms. Learn more about the signs and symptoms of calpainopathy.

Each form of muscular dystrophy is caused by a different genetic defect, which is why there are such large differences between the ages of onset, the types of symptoms, and the progression of symptoms.

Calpainopathy is less severe than more common forms of muscular dystrophy, such as myotonic dystrophy and Duchenne, and unlike Duchenne, it affects both genders. The large differences in the biology of muscular dystrophies make it important to obtain an accurate diagnosis.

Each of these diseases must be studied separately to develop therapeutics that will be effective. One unique feature of calpainopathy is that the mutation affects the calpain 3 enzyme, as opposed to a structural protein, as in many muscular dystrophies. This difference means that therapies that work for one type of muscular dystrophy – or even one type of LGMD – will not necessarily be effective for calpainopathies.

Mutations in the calpain 3 gene cause LGMD2A/R1. This slowly progressive muscular dystrophy affects skeletal muscles but typically not the heart or lungs.

Onset of weakness usually occurs in childhood or early adulthood and first affects the upper leg muscles. Toe walking and protrusion of the shoulder blades (scapular winging) are common, and patients typically lose their ability to walk within 10 to 30 years from the first onset of symptoms.

The most reliable way to diagnose calpainopathy is by performing a genetic test on a blood or saliva sample, which can confirm the presence of one or more mutations in the calpain 3 gene. Alternatively, calpainopathy can be diagnosed by performing calpain 3 immunoblot analysis on tissue collected via a muscle biopsy.

There is currently no treatment that stops the progression of calpainopathy.

However, some interventions may be helpful for certain symptoms of the disease. For example, stretching and physical therapy help prevent or lessen muscle contractures.

Gentle exercise can help to maintain muscle strength and reduce the effects of disease progression. All exercise regimens should be undertaken cautiously and with the guidance of a neurologist, since too much high intensity activity could actually increase the rate of muscle deterioration.

Individuals with calpainopathy should see a neurologist regularly (usually every 6-12 months) to monitor the progression of the disease. The neurologist can make referrals to other specialists and physical therapists as needed and address secondary symptoms which may arise. For example, pulmonary complications may develop.

Coalition to Cure Calpain 3 is actively funding scientific research projects to find a treatment or cure for calpainopathy.

One potential cure cure for calpainopathy would involve gene editing where the CAPN3 gene mutations are “fixed,” or gene therapy where a healthy gene is introduced to replace the defective one. In both cases, cells would begin producing a working calpain 3 enzyme, which would enable the patient’s muscles to function and grow normally.

There is early research currently studying gene editing and gene therapy for LGMD2A/R1. Gene therapies for several other types of LGMDs are currently being tested in clinical trials.

Some scientists believe that stem cell therapy might also be able to cure calpainopathy. Stem cells are cells that have the unique ability to self-renew and to transform into many specialized cell types. In this case, stem cells with a working gene would be introduced into the patient, where they could develop into muscle cells.

It is important to understand that this type of treatment is still in development and has not been proven to treat muscular dystrophy.

“Stem cell clinics” advertising a cure for calpainopathy are exploiting the hopes of patients and their families. Not only are these treatments unproven and unlikely to be beneficial to patients, but they can even harm patients. Additionally, patients who undergo these procedures may be ineligible to participate in future clinical trials.

Scientists are currently attempting to understand the basic workings of the calpain 3 enzyme, including the molecular function(s) it has in muscle cells. Once these roles are understood, researchers will be able to search for drugs which regulate the same functions. This approach will not directly cure the disease, but might improve patient strength and muscle health, and/or slow the progression of the disease.

There are some clinical trials underway to study the usual progression of different forms of muscular dystrophy, including calpainopathy; these are usually called natural history studies.

The best way to stay up-to-date on clinical trials is to join the C3 mailing list and our patient registry, as we will use these mailing lists to keep members informed about the latest research and clinical trials. C3 has compiled information about clinical research and a list of studies that are currently recruiting, which we update regularly.

Join the global C3 Community, a private Facebook group that fosters an environment for patients and their families to provide support to one another and share information.

You can also explore patient stories on our website or share your own story to connect with others through your experiences.