June 24, 2022
This #FactFriday, we’re breaking down the basics of Limb-girdle muscular dystrophy type 2B (LGMD2B) - a progressive, genetic muscle-wasting disease. Cure Rare Disease’s mission is to develop advanced therapeutics for all people impacted by rare diseases.
What is LGMD2B? Mutations in the DYSF gene are responsible for LGMD2B. This gene carries the instructions to make a protein called dysferlin. Dysferlin is found in a membrane called the sarcolemma, which surrounds muscle fibers. The protein is believed to help in repairing the sarcolemma if it is damaged. Some research demonstrates that dysferlin may also play roles in forming muscle fibers and in inflammation.
How is LGMD2B acquired? LGMD2B is a genetic disorder, meaning it is inherited. The abnormal gene, DYSF, is passed down by family members who carry the mutation. People of Libyan Jewish descent are more likely to have LGMD2B. The disease is autosomal recessive, which means an individual must inherit two copies of the mutated gene (one from each parent) to inherit the disorder. To date, over 140 mutations in the DYSF gene have been found to cause LGMD2B.
What are some of the symptoms of LGMD2B? Common symptoms of LGMD2B include muscle weakness in the pelvis and shoulder. The age of onset of symptoms varies, but is often seen between the ages of 20 and 30. Breathing difficulty can occur in later stages of the disease, but it is generally less severe than in other types of muscular dystrophy. Cardiac dysfunction is rarely observed.
What is CRD doing to help LGMD2B? CRD is developing therapies that use recombinant protein therapeutics. Recombinant protein therapy involves inserting the DNA that codes for a protein into bacterial or mammal cells in order to produce the protein in those cells. Gene replacement therapy is not possible to treat LGMD2B because of the large size of the DYSF gene.