UI Study Reveals Important Information About Molecular Defect In Limb Girdle Muscular Dystrophy

March 04, 1999

IOWA CITY, Iowa -- For the first time ever, University of Iowa researchers have confirmed how a protein complex, when defective, causes limb girdle muscular dystrophy.

This information could help scientists to develop new ways to treat limb girdle forms of muscular dystrophy. Limb girdle varieties affect between one in 20,000 and one in 50,000 individuals.

"We have established a cell culture system that we can use to mimic the defect in limb girdle muscular dystrophy," said Kevin Campbell, Ph.D., UI professor of physiology and biophysics, and neurology, and a Howard Hughes Medical Institute Investigator.

The UI findings appeared in a recent issue of the Journal of Biological Chemistry.

Campbell, along with Kate Holt, Ph.D., a postdoctoral fellow in Campbell's lab, used the cell culture system to find out how the protein complex, called the sarcoglycan complex, forms. The sarcoglycan complex, composed of four distinct transmembrane glycoproteins, is part of the dystrophin-glycoprotein complex, a group of proteins located in muscle cell membranes. The dystrophin-glycoprotein complex is thought to stabilize the membrane against contraction-induced damage. Past studies have shown that mutations to the sarcoglycan complex cause various types of limb girdle muscular dystrophy.

Muscular dystrophy is a group of diseases characterized by hereditary progressive muscle weakness and degeneration. The unifying theme among limb girdle varieties of the disease is the initial involvement of the shoulder and pelvic girdle muscles, with relative sparing of most other muscle groups.

Despite rapid advances regarding the genetic defects that cause limb girdle muscular dystrophy, researchers know little about the molecular defects underlying the disease. Through their cell culture model, Campbell and Holt were able to show that complete assembly of the sarcoglycan complex is dependent on the simultaneous synthesis of all four sarcoglycans. Any mutant sarcoglycan blocks the complex formation and its insertion into the plasma membrane. Campbell and Holt's confirmation of how the sarcoglycan complex develops is a step toward learning more about the basic molecular underpinnings of the disease.

"If we can determine where the defect or blockage of the biosynthesis occurs, then that might give us a clue as to a way that we could potentially treat the disease," Holt said.

One potential treatment could involve developing pharmacological reagents that would allow proteins with mutations to be properly expressed, Campbell added.

"We're going to use the model to further study the sarcoglycan complex," Campbell said. "Now that we can synthesize the complex in the laboratory, it will be easier to study the function of these proteins and the molecular pathogenesis of limb girdle muscular dystrophy."
-end-


University of Iowa

Related Muscular Dystrophy Articles from Brightsurf:

Using CRISPR to find muscular dystrophy treatments
A study from Boston Children's Hospital used CRISPR-Cas9 to better understand facioscapulohumeral muscular dystrophy (FSHD) and explore potential treatments by systematically deleting every gene in the genome.

Duchenne muscular dystrophy diagnosis improved by simple accelerometers
Testing for Duchenne muscular dystrophy can require specialized equipment, invasive procedures and high expense, but measuring changes in muscle function and identifying compensatory walking gait could lead to earlier detection.

New therapy targets cause of adult-onset muscular dystrophy
The compound designed at Scripps Research, called Cugamycin, works by recognizing toxic RNA repeats and destroying the garbled gene transcript.

Gene therapy cassettes improved for muscular dystrophy
Experimental gene therapy cassettes for Duchenne muscular dystrophy have been modified to deliver better performance.

Discovery points to innovative new way to treat Duchenne muscular dystrophy
Researchers at The Ottawa Hospital and the University of Ottawa have discovered a new way to treat the loss of muscle function caused by Duchenne muscular dystrophy in animal models of the disease.

Extracellular RNA in urine may provide useful biomarkers for muscular dystrophy
Massachusetts General Hospital researchers have found that extracellular RNA in urine may be a source of biomarkers for the two most common forms of muscular dystrophy, noninvasively providing information about whether therapeutic drugs are having the desired effects on a molecular level.

Tamoxifen and raloxifene slow down the progression of muscular dystrophy
Steroids are currently the only available treatment to reduce the repetitive cycles of inflammation and disease progression associated with functional deterioration in patients with muscular dystrophy (MD).

Designed proteins to treat muscular dystrophy
The cell scaffolding holds muscle fibers together and protects them from damage.

Gene-editing alternative corrects Duchenne muscular dystrophy
Using the new gene-editing enzyme CRISPR-Cpf1, researchers at UT Southwestern Medical Center have successfully corrected Duchenne muscular dystrophy in human cells and mice in the lab.

GW researcher finds genetic cause of new type of muscular dystrophy
George Washington University & St. George's University of London research, published in The American Journal of Human Genetics, outlines a newly discovered genetic mutation associated with short stature, muscle weakness, intellectual disability, and cataracts, leading researchers to believe this is a new type of congenital muscular dystrophy.

Read More: Muscular Dystrophy News and Muscular Dystrophy Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.