A novel approach to treating a genetic condition that causes muscle weakness could soon be on the horizon, after a gene-editing technique called CRISPR was successfully used to alleviate Duchenne muscular dystrophy(DMD) in mice.
DMD is caused by a mutation that inhibits the production of a protein called dystrophin. This vital protein helps to connect muscle fibers to the membranes that enclose them, and is, therefore, essential for ensuring the structural integrity of muscles. In its absence, muscles do not develop properly, causing a range of difficulties in developing children, often preventing them from walking. It can affect the chest and heart muscles, reducing a sufferers life expectancy considerably.
The mutation that causes the condition is carried on the X chromosome, and, therefore, tends to affect boys far more commonly than girls. This is because males have only one X chromosome, while females have two, meaning that girls who inherit one faulty version of the gene for dystrophin are likely to also have one healthy version, and can therefore still synthesize the protein.
Last week, three separate papers were published in the journal Science, each of which outlined an almost identical experiment using CRISPR to treat DMDin mice. CRISPR involves introducing proteins, called Cas9 proteins, into living cells. These proteins then cut the DNA of those cells like genetic scissors, enabling mutations and other undesirable sequences or exons to be removed.
In this case, the researchers inserted the CRISPR-Cas9 complex into a virus which then infected the cells of mouse fetuses. They targeted particular mutated exons on the gene for dystrophin, which were responsible for the mices inability to produce the protein.
The team noted that once these mutations were cut out of the mices genomes, the animals were once again able to produce dystrophin, although sometimes this protein was slightly truncated, since certain stretches of the DNA that encodes it were missing. Even in these cases, however, the mice displayed a significant improvement in symptoms, and did not suffer from DMD.
Though this is encouraging news, a number of stumbling blocks must be overcome before clinical trials on humans can begin. For instance, it is currently not known how the virus used to deliver the CRISPR complex will react with the human immune system. For this reason, Eric Olson, who led one of the three studies, told the New York Times that we need to scale up, improve efficacy and assess safety before any human studies can be launched.