Research Briefs: LGMD, Myofibrillar Myopathy

A new zebrafish research model may speed myofibrillar myopathy research; published results of a gene transfer study in LGMD are now accessible

Article Highlights:
  • Myofibrillar myopathy: A new system of zebrafish research models that develops muscle fiber damage similar to that seen in myofibrillar myopathy has been developed in Australia and is likely to speed research in this subtype of limb-girdle muscular dystrophy.
  • Dysferlinopathies: Dysferlin gene transfer benefited dysferlin-deficient mice, setting the stage for human trials. Published results have been made available online at no charge.
by Amy Madsen on July 18, 2012 - 9:37am

Update (Aug. 8, 2012): This story was updated to reflect the availability of a podcast on the dysferlin gene transfer study.

Zebrafish research models mimic myofibrillar myopathy

Scientists in Australia have developed a system of zebrafish research models that develop muscle fiber damage similar to that seen in myofibrillar myopathy caused by mutations in the filamin C (FLNC) gene. The models are expected to speed research, including the development and testing of treatments.

Myofibrillar myopathies are a group of disorders — all subtypes of limb-girdle muscular dystrophy (LGMD)— in which skeletal muscle fibers disintegrate and clumps of proteins (protein aggregates) form in the contracting part of the muscle fiber (sarcomere).

In humans, the filamin proteins encoded by FLNC are critical for normal muscle development and for maintaining the structural integrity of muscle fibers.

The zebrafish research model known as sot (for "stretched out") carries a mutation in the filamin Cb gene, which is one of two zebrafish versions of FLNC. The other zebrafish version is called filamin Ca.

The researchers examined three zebrafish models:

  • the sot model with the filamin Cb mutation;
  • the flnca model, in which filamin Ca gene activity was decreased; and
  • the flnca+b model that had decreased activity of both the filamin Ca and filamin Cb genes.

Muscle fiber defects and protein aggregates were observed in all three models. Muscle damage was temporary in the sot and flnca models, however, it was permanent and more severe in the flnca+b model.

The observable physical and biochemical changes in the zebrafish models bear a "striking similarity" to those seen in myofibrillar myopathy, the researchers noted, making them "an excellent system" to study the myofibrillar myopathy disease process and potential therapies.

To learn more, see the following:

Published results of dysferlin gene transfer study now available free online

Encouraging results from a gene transfer (gene therapy) study in dysferlin-deficient mice have been made available for viewing at no charge online. The study, published June 15, 2012, in Plos One, focused on mutations in the dysferlin gene that can cause type 2B limb-girdle muscular dystrophy and a distal muscular dystrophy known as type 1 Miyoshi myopathy.

In the study, dysferlin-deficient mice received injections of dysferlin genes packaged into viral delivery vehicles known as AAV2/5 vectors. Robust dysferlin protein production was observed following injections of the genes into the diaphragm and, via the bloodstream, into lower leg muscles. Investigators reported that muscles that received the gene transfer were more resistant to laser-induced injury, and some diaphragm function was restored in the mice.

Study results were presented at the 2012 annual meeting of the American Academy of Neurology, held in New Orleans April 21-28, and reported in Quest News Online.

podcast featuring principal investigator Louise Rodino-Klapac became available in July 2012. It's archived at This Month in Muscular Dystrophy, a service of Nationwide Children's Hospital in Columbus, Ohio.


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