US FDA Grants Expanded Approval of ELEVIDYS Gene Therapy for DMD Patients Ages 4 and Above

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Limb-Girdle Muscular Dystrophy (LGMD)


Throughout the 1990s and the first decade of the 21st century, MDA-supported researchers identified dozens of genes that, when defective, cause LGMD.

This gene identification work continues to the present day, along with research to determine the precise function of these genes so that missing functions can be compensated for and toxic functions can be inhibited.

In the recessive forms of LGMD, it may be possible to insert a new gene to compensate for one that is not working properly. This type of intervention — gene-replacement therapy — has shown promise in a pilot trial in people with the alpha-sarcoglycan-deficient form of LGMD.

In the dominant forms of LGMD, blocking a toxic function using strategies such as antisense oligonucleotides, which keep cells from interpreting genetic information, may become a treatment in the future.

Some genetic mutations, known as premature stop codons, cause cells to stop reading genetic instructions before a fully functional protein has been synthesized. A drug that causes cells to “read through” these stop codons is being tested in another form of muscular dystrophy (Duchenne) and may have some application in LGMD.

Some genetic mutations add or remove DNA and change the way cells interpret the information in a gene. In Duchenne muscular dystrophy, clinical trials are underway to evaluate compounds that coax cells to skip over these error-containing DNA regions, or exons. This research also may have relevance for LGMD treatment.

Still another strategy is to use stem cells to help ailing muscles regain strength. Stem cells are early-stage, flexible cells that can give rise to mature muscle fibers. They are found in muscle tissue and other places in the body, and scientists are working to determine which cells are the safest and most effective to test in people with LGMD and other diseases.

An additional avenue of investigation is blocking a natural protein called myostatin, which puts a brake on muscle growth. Growth hormone is also being studied as a treatment for LGMD, but effectiveness and safety remains to be determined.

MDA supports scientists and clinicians conducting LGMD research. Among recent projects: 

  1. Dr. Aron Beedle at the State University of New York at Binghamton University aims to test a pharmacological inhibitor for mTOR to block common intercellular pathways that will improve muscle function, reduce pathology, and increase lifespan.
  2. Dr. Chakravorty and colleagues at Emory University in Atlanta, Ga., plan to use a discovery-driven approach to correlate gene networks with disease phenotype using patient muscle biopsy tissue to test the hypothesis that complex genetic pathways contribute to the Pompe and LGMD mechanism with high prevalence, potentially by synergistic effects of multiple genes.
  3. Dr. Davies and colleagues at Queen’s University in Kingston, Ontario, will determine the structure of calpain-3 by X-ray crystallography. The goal is to have a complete map of the enzyme as well as binding partners that help the enzyme regulate its action. Locating the mutations on the map will help explain what causes the enzyme to fail and predict which cases of LGMD2A might be treatable with small molecules to stabilize the enzyme.

Sanofi Genzyme is collaborating with PerkinElmer Genomics to offer a complimentary genetic testing program called The Lantern Project that offers diagnostic testing for several disorders, such as Pompe disease, LGMD, Gusher, and others.

The Lantern project helps patients to get a better and more precise genetic diagnosis. Patients with clinical symptoms suggesting LGMD or those who has unspecified LGMD genetic diagnosis, are eligible to apply. Additionally, patients with the physical manifestation of Pompe disease, or those who screened positive for Pompe are welcome to participate as well. For more details about the program please visit the Lantern Project Website.

Participants will be tested against 98 different genes that are known to cause LGMD, Pompe (GAA genetic variants), other myopathies, and myasthenic syndrome in order to provide them with better diagnosis.

The Lantern project offers limb-girdle muscular dystrophy (LGMD) genetic testing program at no cost to families.

To read the most current news about any of the research strategies mentioned here, use the MDA search box found at the top of this page.

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