Melissa Spencer, professor of neurology and neuromuscular program director in the David Geffen School of Medicine at UCLA, has received a five-year, $2.8 million grant from the National Institutes of Health to develop targeted gene therapy for a rare form of muscular dystrophy called limb girdle muscular dystrophy type 2A.

Limb girdle muscular dystrophy type 2A is an inherited disease that results from defects in the gene that encodes a protein called calpain 3. There is no cure and people with the disease are usually confined to wheelchairs by middle age.  

Spencer and her collaborators at the University of Washington, with whom she will share the grant, are working on a gene therapy to restore the missing calpain 3 protein to the muscles of the arms and legs. The concern with developing this missing protein is that if it goes to the heart, it can cause serious damage.

To prevent this, the researchers must design a delivery system that allows the gene to do its work only in the cells where it’s needed. Every gene in the body is associated with a short sequence of DNA called a promoter. This promoter tells the cell to “turn on” that gene, and this is how the body can make specialized cells, like heart, brain and bone. Each cell type activates different genes, and promoter sequences are key to that specialization.

The team will test many different promoters to find one that will tell skeletal muscle cells, but not heart cells, to turn on the gene. With the right promoter sequence, “even if [it] gets to the heart, the gene won’t be active,” Spencer said.