Muscular dystrophy patient who was first in line for a custom CRISPR therapy dies

Few details are available about Horgan’s death. It’s unclear when, or even if, he received the experimental therapy. A spokesperson for UMass Chan Medical School deferred all questions to Cure Rare Disease. A spokesperson for organization said no further details are being shared at this time. Richard Horgan did not respond to request for comment.

The death was first reported by the Associated Press on Friday. Cure Rare Disease posted a statement on its website earlier in the week confirming the death. The organization said that “multiple teams across the country” are working to understand what happened, but cautioned that it “could take up to four months” to find answers.

Richard Horgan founded the nonprofit in 2017 when he was a student at Harvard Business School. His goal was to find a treatment for his brother’s form of Duchenne muscular dystrophy, which is caused by a mutation that impeded his ability to make a crucial muscle protein called dystrophin.

Terry had long been too old to participate in clinical trials of experimental therapies for the disease, which are often geared towards young boys.

By 2019, his brother had assembled a team of scientists at Charles River Laboratories, UMass Chan Medical School, Yale University, and other institutions to help design a bespoke therapy for Terry. The treatment used a new version of CRISPR to turn on a backup copy of the dystrophin gene that mysteriously lies dormant in our muscles.

After more than three years of crafting the therapy, testing it in the lab, and manufacturing it, the US Food and Drug Administration gave the group a go-ahead to administer the therapy to Terry this summer. Soon after Cure Rare Disease announced that positive news in August, Richard Horgan told the Globe that his brother should “soon” get the treatment.

Although several companies are developing treatments based on CRISPR gene editing technology, and early data suggests that they might be safe and effective, there are no approved drugs based on the approach.

The clinical trial was to be the first time anyone got a gene editing therapy for muscular dystrophy. It was the first time that a gene editing therapy was custom-made to address a single individual’s unique genetic mutation. And it was the first time that a new version of CRISPR technology, broadly known as epigenome editing, was tested in humans.

Epigenome editing aims to dial the expression of genes up or down. Many scientists hope that the approach proves to be a safer alternative to gene editing therapies that make permanent changes to DNA itself. It is unclear whether this new technology played a role in Terry’s death.

One aspect of the therapy that was not entirely new was the use of engineered viruses to deliver instructions for the gene editing therapy into Terry’s cells. Like many gene therapy companies, Cure Rare Disease packaged the therapy in adeno-associated viruses. High doses of gene therapies based on these viruses have been linked to deaths in other experimental gene therapies.

Experts not involved in the trial have also cautioned that Terry was much older than most participants in studies of MD drugs.

Monkel Lek, a scientist at Yale School of Medicine who designed the therapy, and Dr. Brenda Wong, a physician who specializes in muscular dystrophy at UMass Chan Medical School and was in charge of the clinical trial, did not respond to requests for comment.

Cure Rare Disease said in its statement that it was committed to sharing its findings with other scientists, and that it would continue working on 18 additional experimental therapies in its pipeline.

Ryan Cross can be reached at [email protected]. Follow him on Twitter @RLCscienceboss.