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What We Owe Terry Horgan: Reflections from Providers, Family, and Scientists

October 12, 2023

I first saw Terry Horgan as a patient. I was filling in as the pediatric pulmonary specialist in the UMass-Duchenne Muscular Dystrophy (DMD) center, an excellent multidisciplinary clinic exclusively for DMD patients that is run by Dr. Brenda Wong. My role on this one visit was to evaluate every patient's respiratory status and make recommendations for their care. During that visit I also met Terry's brother and his mother. I learned that Terry's brother, Richard Horgan, was working to create a gene therapy for Terry. In my research career as a gene therapy scientist, I knew that several DMD gene therapies were in the pipeline, but DMD was not a disease that my own laboratory had worked on, so I had only followed that work from distance. After making my pulmonary recommendations, I wished them all well, and did not see them again for some time.

Years later, Dr. Wong contacted me to tell me that she wanted to treat Terry with an innovative “bespoke” gene therapy, one designed just for his own personal mutation. This approach was chosen because Terry, at age 27, was too old for any of the proprietary gene therapies that were in clinical trials. I gave Dr. Wong and her team advice from time to time but was not deeply involved with the case until September 2022, after the therapy had been manufactured. In the weeks before Terry's therapy was given, I became more involved, providing my own insights on preventing immune complications in his case. Our concerns about such risks were amplified in his case because Terry's age and stage of disease gave him less physiological reserves to deal with adverse effects from the therapy. After suggesting as many safeguards as I could think of, I also made sure to be a part of the informed consent process with Terry and his family. I wanted to make sure that he was fully informed of the risks.

The rest of the story is, unfortunately, familiar to many in the field. Terry received the gene therapy, but began experiencing cardiac complications in the first few days afterward. As his condition gradually worsened, multiple additional doses of immune-suppressive, anti-inflammatory, anti-cytokine, and anti-complement therapies were given. Despite intensive care unit support, mechanical ventilation, and extracorporeal membrane oxygenation at UMass and Boston Children's hospitals, Terry died. A limited autopsy was done at Boston Children's hospital, which showed that Terry had suffered from adult respiratory distress syndrome most likely as part of a “cytokine storm” that the vector had triggered. This process had caused his lungs to fill with fluid and had put stress on his heart that it simply could not take.

After Terry passed, there was flurry of commentary among scientists and in the press. Various parties sought to use Terry's case a “talking point” in an argument about the risks of gene therapy or of CRISPR-based therapies or of some other aspect of the clinical trial process in the United States. Some drew parallels to Jesse Gelsinger, a young man whose death in one of the earliest recombinant adenovirus gene therapies has been viewed as a trigger for the decline in support for gene therapy in the early 2000s.

In my view, it is deeply wrong to turn the suffering endured by Terry Horgan and his family into a punch line. Terry was, in fact, a bright and courageous man who understood that he as taking a serious risk with his life by undergoing this experimental therapy. Terry understood that he might die from side effects of the therapy. Yet, I never once heard him waver from his resolve to try it. He made it very clear that he wanted to do this whether it helped him personally or not. He recognized that there were no therapies available that were going to help DMD patients in their 20s. He was determined to “rage, rage, against the dying of the light.” He and his family wanted the therapy to work for Terry, but at the very least they were bravely resolved to have his participation in this trial provide data to inform future trials for other DMD patients who currently have no good options.

Since Terry's passing, I have also reflected on all these events. Although Terry never expressed regrets, I deeply regret that the therapy did not work for him. I regret that neither I, nor any other member of the team, was smart enough to prevent or reverse the terrible consequences that ensued. But along with that regret, I also owe Terry many things. I owe it to him to get every possible bit of data from his case published and disseminated to all gene therapy scientists working in this field. I owe it to him to do my part in scientific discussions of how to overcome obstacles preventing older DMD patients from gaining the benefits of gene therapy. I owe it him to speak out on behalf of patients who are being left behind as gene therapy advances, because they are too old or too sick or have a disease that is too rare to make for a neat and easy gene therapy success story.

In this field, we have a moral obligation to make gene therapies accessible to all, regardless of disease rarity, financial circumstance, or geographic location. I owe it to him to remind myself and my colleagues that our patients are people, not just experimental subjects. We have been granted the privilege to access their outcomes as data to inform the science of gene therapy, but we owe it to them to respect the fact that they are each unique persons with thoughts, hopes, and dreams for the future. Patients should never be used as punch lines. In the end, Terry Horgan was not a victim, he was a warrior. We should all recognize that fact and respect him for it.

Terry Flotte, MD

What We Owe Terry Horgan: Reflections from Providers, Family, and Scientists.Human Gene Therapy.ahead of print



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