CRISPR-Cas9 for Duchenne muscular dystrophy: between hype and hope

Blog by Annemieke Aartsma-Rus

With the arrival of the CRISPR-Cas9 technology it has become much easier to repair mistakes in the DNA. This provides potential for therapy development for genetic diseases, such as Duchenne muscular dystrophy. Scientists and the media even refer to the “CRISPR Cure”. However, the question is whether this is justified?

On August 30 2018 the scientific journal Science published an article about the use of the CRISPR-Cas9 technology in dogs with Duchenne muscular dystrophy. Similar to Duchenne patients, these dogs lack the protein dystrophin due to a mistake in the DNA that makes the genetic code unreadable. Using the CRISPR-Cas9 technology a small piece can be removed from the gene to make the code readable again. This would allow the production of a shorter, but partially functional dystrophin protein.

Dog muscles
Three dogs were treated with a local injection of viruses carrying the CRISPR-Cas9 system. However, since Duchenne is a disease that affects all of the 750+ skeletal muscles, systemic treatment is required. Hereto, the researchers injected viruses with the CRISPR-Cas9 system intravenously into the circulation of two dogs. One dog received a relatively low dose and the other a high dose. After two months, the muscles of the dogs were analysed. Hardly any dystrophin was found in the muscles of the dog that received the lower dose. However, dystrophin was detected for the dog that received the higher dose, albeit at varying levels in different muscles.

The scientists who performed the study were carefully optimistic and indicated that studies in patients are far off. This was only a short study in a very small group of dogs. Furthermore, the safety of the CRISPR-Cas9 system needs to be evaluated further, since it recently became clear that this system can cause both intended and unintended changes in the DNA.

With the publishing of the research article, Science published their own commentary. The author states here that CRISPR-Cas9 solves muscular dystrophy in dogs. But, he adds, studies in humans will not happen in the near future. In the hours after the commentary appeared online, headlines were copied and within a day, headlines appeared about how the dogs were cured and how trials in patients are imminent. These headlines were of course picked up by the parents of Duchenne patients and shared widely on the internet and social media.

Wrong expectations
The problem of this media-hype is that it sets the wrong expectations with the patients and their families. The CRISPR-Cas9 technology cannot cure Duchenne: the protein produced will only be partially functional. It can be compared with the dystrophin that Becker muscular dystrophy patients produce. Although the symptoms start later in life and the disease progression is slower for Becker patients, they do have a debilitating muscle disease. In addition, the CRISPR-Cas9 treatment will not restore the muscle mass and muscle function already lost by Duchenne patients.

So let’s be clear: even if CRISPR-Cas9 will become available for Duchenne patients, it will unfortunately not be a cure. And while one always should have hope, having false hope is not productive.

Annemieke Aartsma-Rus is professor of Translationel Genetics. One of her research focuses is developing therapies for Duchenne spierdystrofie