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Rewriting Life

Startup Aims to Treat Muscular Dystrophy with CRISPR

Patients groups are backing gene-editing as potential “home run” against disease.

A foundation representing boys dying from muscular dystrophy says it will try to cure the disease using CRISPR, a breakthrough method of correcting DNA.

CureDuchenne, a patient charity based in Newport Beach, California, says it will spend $5 million to finance a new startup company, Exonics Therapeutics, based on research in which scientists cured mice of muscular dystrophy by altering the DNA letters inside their cells.

“We are looking for a home run—nothing less than correction of the DNA error,” says Jak Knowles, a doctor who is acting as CEO of the new company. 

The company hopes to move as quickly as possible toward a test of CRISPR in boys with Duchenne muscular dystrophy, Knowles says. CRISPR technology is a novel and potent way to precisely rewrite DNA. Delivered into the muscles of affected boys, it may be able to repair the genetic error that causes the fatal condition, afflicting about one in 3,500 male births.

The formation of Exonics shows how patients are placing their hopes on CRISPR and also how some charities have started financing drug development directly, a trend known as “venture philanthropy.” That practice can pay off handsomely. In 2014, the Cystic Fibrosis Foundation sold off rights to a drug, Kalydeco, for $3.3 billion after putting $150 million behind its development.

Knowles says the $5 million investment in Exonics is the largest ever by CureDuchenne in a single company, reflecting its belief that gene editing could go far beyond existing drugs for Duchenne. “CRISPR is not some repurposed drug doing the bare minimum,” says Knowles. “It’s something with high impact.”

Exonics will advance research underway at the University of Texas Southwestern Medical Center, where scientist Eric Olson and colleagues have cured mice of muscular dystrophy using CRISPR, stirring intense hopes among patients. MIT Technology Review profiled Olson’s efforts last year.

The protein dystrophin appears (red) in a microscopic image of normal muscle fibers. Patients with muscular dystrophy lack dystrophin.

Olson says his next step is to treat larger animals, such as dogs or monkeys. “If that is as positive as we think it will be, we would move to humans,” says Olson, who is a cofounder of the company and owns a stake in it. Exonics did not provide a timeline for when a human study could begin.

Olson says he had the chance to raise money from traditional investors or to partner with a large biotech company, but decided a company backed by a patient group would move the treatment along faster. “I get e-mails from mothers every day,” says Olson. “I think this enables me to move forward in the most effective way.”

Officially, CRISPR drug technology is dominated by three public biotechnology companies—Editas Medicine, Intellia Therapeutics, and CRISPR Therapeutics—all based in Cambridge, Massachusetts, and which have raised more than $1 billion among them.

Two, Editas and CRISPR Therapeutics, list muscular dystrophy among the diseases they are interested in, but it’s not a top priority. The companies are primarily developing treatments for blindness, blood disorders, liver disease, and cancer.

Knowles says CureDuchenne feared the muscle disease was not receiving enough attention by the bigger biotechs. “We want to move fast and we don’t have the conflict of priorities a larger company does,” says Knowles.

More patients groups could soon hatch their own break-away CRISPR plans. That’s because the technique is versatile enough that it could help with scores of ultra-rare inherited diseases, many of which are now untreatable.

The gene that goes wrong in Duchenne muscular dystrophy, called dystrophin, was discovered 30 years ago. Boys who lack a working copy of dystrophin become paralyzed when their muscles waste away and usually die of heart failure before they turn 25.

Olson and others have already shown CRISPR technology can repair the dystrophin gene in mice. But gene-editing ingredients have never been directly injected into a living person, which is Exonics’s goal. Patients would receive an injection of trillions of viruses, each harboring the instructions to edit the DNA of the dystrophin gene in their muscle cells.

If enough muscle cells get corrected—perhaps 15 percent—the progression of the disease could be halted, Olson thinks.

Because many different mutations in the dystrophin gene can lead to muscular dystrophy, initially a CRISPR treatment wouldn’t fix all of them. Olson says the treatment he’s working on targets part of the gene known as “exon 51” and, if it works, would help about 13 percent of boys with the disease.

Drug development experts caution that CRISPR studies may not work out as planned. “There is a concern in the Duchenne community that patients have become overly excited that CRISPR will let them get up and walk,” says Susan J. Ward, executive director of the Collaborative Trajectory Analysis Project, which helps drugmakers develop better ways of testing new drugs.

In fact, delays lasting years, or decades, are common when scientists attempt to craft treatments from a new technology, only to encounter unexpected roadblocks or safety issues. “I think CRISPR is truly exciting,” says Ward. “But it’s not a slam dunk yet.”

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The protein dystrophin appears (red) in a microscopic image of normal muscle fibers. Patients with muscular dystrophy lack dystrophin.
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