Researchers link the death in the gene-editing study to a virus used to deliver the treatment, not CRISPR

The only volunteer in a gene-editing study targeting a rare form of Duchenne muscular dystrophy likely died after having a reaction to the virus that delivered the therapy into his body, researchers concluded in an initial study.

Terry Horgan, 27, of Montour Falls, New York, died last year during one of the first tests of a gene-editing treatment designed for a person. Some scientists have wondered whether the gene-editing tool CRISPR played a role in his death. The tool has transformed genetic research, sparked the development of dozens of experimental drugs and won its inventors the Nobel Prize in 2020.

But researchers said the virus used to deliver the treatment into the body because it usually doesn’t make people sick combined with its condition triggered the problems that ultimately killed it.

Horgan appears to have had a more severe immune reaction than others who received similar or slightly higher doses of the virus, the authors wrote in the study, which has not yet been peer-reviewed.

Horgan was enrolled in an early stage safety study approved by the Food and Drug Administration. He was sponsored by Cure Rare Disease, a Connecticut-based non-profit organization founded by his brother Rich, to try to save him from the muscle-wasting disease caused by a mutation in the gene needed to make a protein called dystrophin.

In a statement, Rich Horgan thanked the research team led by the University of Massachusetts Chan Medical School and Yale University for a thorough and comprehensive investigation that provided valuable insights. He added, “On a personal note, this study is another important step in honoring Terry’s legacy and his commitment, as well as our entire family, to the rare disease community.

The therapy Horgan got aimed to use CRISPR to boost a form of the protein dystrophin. The process began with suppressing Horgan’s immune system to prepare her body for the therapy, which was administered intravenously with a high dose of what’s known as an adeno-associated viral vector, or AAV, according to Cure Rare disease..

But Horgan soon started having problems, going into cardiac arrest six days after treatment and died two days later of organ failure and brain damage. Due to the timing of the symptoms and the fact that the researchers were able to find very little gene-editing enzyme in his body, they concluded that the therapy had not yet been activated.

This isn’t the first time viral vectors have been implicated in a gene therapy death. In a major setback for the field, 18-year-old Jesse Gelsinger died in 1999 during a study aimed at battling his rare metabolic disease. Scientists later learned that his immune system overreacted to the virus used to deliver the treatment. The virus used in the Horgans trial is considered to be safer but it is not without its problems.

People have tried to make carriers safer, but they still remain a challenge, said Arthur Caplan, a medical ethicist at New York University who was not involved in the study but has been following the case closely. We really don’t understand why some people get into trouble and others don’t. We don’t know if it’s their underlying disease, some comorbidity, or some weird immunology.

Rich Horgan said they plan to submit the study to a peer-reviewed journal. Meanwhile, Cure Rare Disease said it will use alternative viruses for the other treatments it is looking to develop.

Dr. Terence Flotte, dean of UMass medical school and senior author of the study, said he hoped it would lead to more research on how to identify subsets of patients who may be prone to severe and unexpected reactions like this one.

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