Therapeutic Strategies

Shown in gray below is the chain of events that causes disease in dysferlinopathy patients. In red are potential therapeutic approaches that may block this disease pathway and improve pathology. This is a dynamic illustration that will continue to change with increasing knowledge of dysferlin biology and ideas for novel interventions, and how each strategy blocks the progression of disease. Hover your mouse over the strategies in the diagram for explanations.

Gray = Disease pathway
Red = Therapeutic strategy


Gene editing involves triggering muscle cells to edit their own DNA and change their dysferlin gene mutations back to the correct dysferlin DNA sequence. This strategy is still in development.
Stop codon readthrough involves using a small molecule to make cells ignore premature stop mutations while producing proteins, so that full-length dysferlin protein is produced instead of truncated protein. This strategy is currently in clinical trials for cystic fibrosis and Duchenne muscular dystrophy.
Exon skipping involves giving cells instructions to skip a portion of the dysferlin coding sequence - a portion that contains a mutation - while producing the dysferlin protein, so that (almost) full-length dysferlin is produced instead of truncated protein. This strategy is currently in clinical trials for Duchenne muscular dystrophy.
Chaperones are small molecules or proteins that can bind to and stabilize the normal 3-dimensional shape of proteins such as dysferlin, so that missense mutants are more likely to fold correctly instead of misfolding. This strategy is currently in clinical trials for cystic fibrosis but is still in development for dysferlin deficiency.
Gene therapy involves adding a new copy of the dysferlin gene (without mutations) to a patient's muscle cells, so that functional dysferlin protein can be produced from this new copy despite the mutations in the original two copies of a patient's dysferlin gene. This strategy is currently in clinical trials for Duchenne muscular dystrophy.
Stem cell therapy involves giving patients new muscle stem cells carrying normal copies of the dysferlin gene, so that these stem cells will give rise to new muscle fibers that can produce functional dysferlin protein. This strategy will soon be in clinical trials for Duchenne muscular dystrophy.
Repair-mediating proteins are other proteins coded by the genome that may be able to substitute for the function of dysferlin in membrane repair, and whose expression might be turned on or increased in muscle cells. Repair-mediating drugs are small molecules that may enhance cellular membrane repair processes or may improve the membrane fusion step of cellular membrane repair even in the absense of dysferlin. This strategy is still in development.
Repair-mediating proteins are other proteins coded by the genome that may be able to substitute for the function of dysferlin in membrane repair, and whose expression might be turned on or increased in muscle cells.Repair-mediating drugs are small molecules that may enhance cellular membrane repair processes or may improve the membrane fusion step of cellular membrane repair even in the absense of dysferlin. This strategy is still in development.
Membrane stabilization involves using small molecules and lipids to stabilize the muscle cell membrane and either help the the membrane resist tears or help it close tears on its own without requiring specific cellular repair mechanisms. This strategy is still in development.
Calcium regulation involves interfering with cellular signalling pathways and with calcium release from compartments within a cell, so that muscle cells do not necessarily die in response to membrane damage. This strategy is still in development.
Cell death regulation involves changing the way that muscle fibers die - from uncontrolled death to a controlled death pathway that does not cause inflammation or additional damage to other nearby cells. This strategy is still in development.
Immune modulation involves using drugs to suppress inflammation so that a patient's immune response to degenerating muscle does not cause additional death of muscle cells. This strategy is used to partially manage other muscular dystrophies but is still in development for dysferlin deficiency.
Increased regeneration involves stimulating a patient's existing muscle stem cells to form new muscle fibers at a faster rate, in order to replace the fibers that are dying. One method of implementing this strategy is currently in clinical trials for a range of muscular dystrophies.