Startups, BioPharma

Can CRISPR deliver real progress in Duchenne muscular dystrophy?

After two painfully incremental drug approvals, the Duchenne muscular dystrophy field is still searching for a therapy that can substantially improve patients’ lives and lifespan. Sounds like a job for CRISPR/Cas9.


After two painfully incremental drug approvals, the Duchenne muscular dystrophy (DMD) field is still searching for a therapy that can substantially improve patients’ lives and lifespan.

Enter Exonics Therapeutics and CRISPR/Cas9.

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On Monday the Boston, Massachusetts startup officially launched with $5 million in seed funding from CureDuchenne Ventures, the investment arm of a non-profit DMD advocacy group.

Exonics comes as an extension of the work of Scientific Founder and Chief Science Advisor Eric Olson at the University of Texas Southwestern Medical Center. In an email forwarded by a company representative, Olson said the company wants to use CRISPR/Cas9 technology to permanently fix the faulty gene.

“It is our hope that a one-time treatment with a gene editing therapy could provide a lifelong benefit to Duchenne patients, preventing further decline.”

Globally, DMD affects around one in every 3,600 male infants, making it the most common form of muscular dystrophy. It is caused by defects in the gene coding for a protein called dystrophin. Without dystrophin, the patient’s muscle cells are fragile and easily damaged. Over time they degenerate and progressively weaken.

On the surface, the fatal disorder seems like a good candidate for gene therapy. The challenge, however, comes with the extreme length of the dystrophin gene. At 2,300 kilobases (a measure of 1,000 nucleic acid molecules) it happens to be one of the largest genes in the human genome.

The size of the gene has confounded traditional gene therapy approaches, which use a vector or virus to carry a normal copy of the gene into the relevant cells (in this case, muscle cells).

CRISPR/Cas9 enables a more targeted approach. Guiding RNA are used to move the gene editing complex towards a specific stretch of DNA. The Cas9 enzyme then snips both ends of the gene fragment, triggering genome repair mechanisms within the cell.

Olson’s past work used an adeno-associated virus to deliver a CRISPR/Cas9 complex into the relevant cells, where it can identify and correct the mutations that block the production of dystrophin

Based on its preclinical data, Exonics estimates that the CRISPR gene therapy approach could permanently treat up to 80 percent of children who suffer from Duchenne — if it proves successful in human trials.

By contrast, Sarepta Therapeutics’ DMD drug Exondys 51 (eteplirsen), is approved for approximately 13 percent of the population.

As for the high-profile CRISPR patent interference dispute, Exonics’ president and interim CEO Jak Knowles said in an emailed statement that the company is concerned with the science, not the IP debates.

“Exonics is focused on generating robust preclinical data that supports the development of a safe and efficacious therapy and advancing our Duchenne program thoughtfully and expeditiously to the clinic,” Knowles said. “We, as many others, believe that the broader intellectual property debate around technologies like CRISPR/Cas9 should not delay the progress of drug development.”

Photo: wildpixel, Getty Images