CRISPR-Cas9 and new promising advances for Duchenne muscular dystrophy

The revolutionary genetic technique CRISPR-Cas9 is gaining more and more attention. Some new scientific studies have just been published which present the work which has been carried out in treating a very serious pathology, thus far, unfortunately considered incurable: Duchenne myopathy.

This neuromuscular disease is marked by severe muscular weakness, and progressive pathological atrophy in all body muscles. This genetic disease is set off by gene mutations of the DMD gene, which codes for an essential muscular functioning protein: dystrophin. This very large gene is carried by chromosome X.

Three independent research teams working on this subject, published simultaneously in the review Science the result of their work carried out on mice with CRISPR-Cas9, a technique which opens unprecedented possibilities for correcting those mutations. This genetic engineering technique allows targeting DNA zones to be cut out in order to inhibit or replace the defective gene. Thus the three teams worked on cutting out the defective gene in the DNA sequence concerned. In the absence of the defective DNA segment, the muscular cell produces a shorter, yet functional dystrophin protein, visibly allowing the mice to recuperate some strength.

At first, one of the teams performed this genome modification experiment on a mouse embryo (fertilized egg), thus creating a subject considered to be healthy. But this modification becomes transmissible to future generations, and these experiments do not respond to the needs of patients with muscular dystrophy. This team then worked on modifying the genome of the muscular cells of the young mouse. To do this, they used an inoffensive virus carrying the genome modification system capable of infecting the muscular cells in the entire body of the mouse to depose in each one these “scissors” used to cut out the DNA. The cells of the genome thus “repaired” then started coding a functional dystrophin.

The two other teams conducted similar experiments, targeting other zones of the defective gene. But one of the teams, decided to go even further, by using a virus capable of carrying the CRISPR-cas9 equipment to the heart of the germ cells which produce the new muscular cells, to modify the genome. Treating the muscular germ cells of a patient could achieve a more permanent therapeutic result, than the correction of ordinary, mature muscular cells, which are renewed at a rapid pace in patients with muscular dystrophy compared to patients who do not suffer from this disease.

The three teams filed patents. Even if a genetic therapy for muscular dystrophy can be envisioned, there is still considerable work to be done before human clinical trials can begin. It remains to be seen: how the human immune system will react to components from the gene modification system or to the modified dystrophin proteins to which it is not accustomed.

Les Echos, a daily newspaper, underlines that “At the forefront of the fight against genetic diseases, genome modification constitutes a formidable weapon in the hands of doctors.” This genome modification technique is revolutionary and lets one imagine countless potential therapies, as in these studies. It depends on how the technique is used.

Let us keep in mind that the CRISPR-Cas9 technique leads to major ethical questions if used on human embryos or human germ cells. “It’s a red line not to be crossed” recently recalled, Tugdaul Derville, Alliance VITA’s General Deputy. “Applying these techniques of editing DNA to human reproductive cells or human embryos legitimately causes dizziness. We are risking the emergence of custom-made babies and the modification, in a transmissible manner, of the human genome, which constitutes a world heritage of humanity and which therefore deserves all our necessary precautions.”


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