Steve Wilton, foundation chair in molecular therapies at the Centre for Comparative Genomics at Murdoch (Australia) University, was awarded an MDA research grant totaling $300,000 over a period of three years to develop exon-skipping compounds for the less common mutations causing Duchenne muscular dystrophy (DMD).
Exon skipping has emerged as a promising therapeutic strategy for DMD. An exon is a section of a gene; multiple exons are combined to make the instructions for a protein. In DMD, a mutation that affects one or more exons of the dystrophin gene can prevent the protein from being made properly.
By blocking an exon or exons near the mutation, it is sometimes possible to restore the cell’s ability to create a smaller-than-normal, but still functional, dystrophin protein.
Different people carry different mutations and will require that different exons be blocked to treat those mutations. Experimental treatments that block (“skip”) exon 51 are now being tested in clinical trials, and results from early trials indicate these treatments may be beneficial.
But these treatments can only treat those who can benefit from blocking exon 51, Wilton points out, accounting for about 15 percent of all cases of DMD.
“Individuals with different mutations in their dystrophin gene need to have other morpholino oligos [the name for the exon-skipping treatment] designed to address their dystrophin mutations. Our project will extend exon skipping to the rare exons and other mutations that require multiple exons to be removed.”
The goal, he says, is to have these treatments ready to test if the current exon 51-targeting therapies continue to show promise in the clinic.
“If this therapy is shown to be able to slow or halt the progression of DMD, we want to have lead morpholino candidates ready to treat as many other DMD mutations as possible.”
Funding for this MDA grant began August 1, 2013.