The sole volunteer in a trial to test an experimental and controversial gene-editing therapy has died of unknown causes.
Terry Horgan, from Montour Falls, New York, enrolled in the study in late August with the hope of treating Duchenne muscular dystrophy (DMD).
The 27-year-old was one of the first Americans to be treated with CRISPR, which works by editing genes by precisely cutting DNA and letting the natural repair process take over.
His rare genetic muscle wasting disease is caused by a mutation in the gene needed to make a protein called dystrophin.
As of now, the exact cause of Horgan’s death last month remains unclear.
But his death raises questions about the broader outlook for gene-editing therapies, which have raised hopes among many families facing rare and incurable diseases.
At this time, it’s unclear whether Horgan received the treatment and whether CRISPR, other aspects of the study, or the disease itself contributed to his death.
Deaths are not unheard of in clinical trials, which test experimental treatments and sometimes involve very sick people.
But CRISPR trials are relatively new. And Fyodor Urnov, a CRISPR expert at the Institute for Innovative Genomics at the University of California, Berkeley, said any death during a gene therapy trial is an opportunity for the field to have a reckoning.
“The first step is to mourn the death of a brave human soul who agreed to basically be a participant in an experiment with a human being,” Urnov said. “But then, to the extent that we can, we need to learn as much as we can to forge a path forward.”
Terry Horgan, 27, died last month while taking part in a trial of a new gene-editing technology aimed at treating his Duchenne muscular dystrophy, a fatal genetic disorder that causes muscle wasting.
CRISPR is a way of finding a specific strand of DNA in a cell and then removing, adding, or altering sections of the DNA sequence. It has the potential to transform the way diseases such as cancer and neurodegenerative disorders are treated.
DMD is a genetic disorder that affects around 20,000 boys each year. The mess occurs in one in 3,500 to 5,000 newborns worldwide.
The condition is caused by a mutation on the X chromosome that creates problems making the protein dystrophin, which helps build muscle cells and keep them intact.
A shortage of dystrophin causes a person’s muscle fibers to break down when exposed to the body’s enzymes, causing them to lose the strength needed to perform daily tasks.
The condition occurs mainly in men and is usually diagnosed early between the ages of two and six.
DMD is usually treated with a corticosteroid, which slows the progression of the disease.
The introduction of corticosteroids can alter the levels of the hormone testosterone. That can lead to delayed puberty.
Many DMD sufferers die in their teens. However, medical advances in care have extended the lifespans of many patients into their 30s, 40s, and 50s in recent years.
Cure Rare Disease, which funded the study and was founded by Horgan’s brother, said in a statement: “Terry’s loss is heartbreaking and he will be remembered as a hero.”
cure rare diseases said Multiple investigative teams across the US are reviewing the probable cause of Horgan’s death, adding: “This is a complex task and could take up to four months.”
Cure Rare Disease, which supports the development of 18 other therapies, said in its statement that the teams’ work is essential not only to shed light on the study’s outcome, but also “on the challenges of gene therapy in general.”
Investigators have provided an incident report to the Food and Drug Administration (FDA), as required for clinical trials.
The agency also approved the trial, which was led by Dr. Brenda Wong, a pediatric neurologist at the University of Massachusetts.
CRISPR has been praised and criticized since it was first introduced in 2012.
The technology works by finding a particular strand of DNA in a cell and then altering or removing that DNA.
Some scientists believe gene-editing technology could one day help cure cancer or HIV patients by allowing doctors to repair faulty DNA.
The inventors of the tool won a Nobel Prize in 2020.
CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, has the potential to transform medicine by helping to treat and prevent serious diseases such as cancer and neurodegenerative diseases.
Despite its promise, CRISPR is not perfect.
Dr. Arthur Caplan, a medical ethicist at New York University, saying Associated Press: ‘We know that CRISPR may miss its target. We know that CRISPR can be partially effective. And we also know that there may be problems with… the viral vectors that deliver the therapy in the body.
Safety issues in gene-editing technology research are not unknown.
There is a risk of mistakenly changing DNA or RNA in regions other than the target site, which could lead to unwanted side effects. For example, unintentional modification of a tumor suppressor gene can cause cancer.
A major scandal rocked the world in 2019 when Chinese scientist He Jiankui was jailed after modifying the DNA of twins Lulu and Nana before they were born to make them resistant to HIV.
His work to manipulate the genes of human embryos was deemed “monstrous”, “unethical” and “highly dangerous”.
A group of more than 100 scientists in China criticized He’s work in 2018: “Performing direct human experiments can only be described as insane.”
The group added: ‘Pandora’s box has been opened. We could still have a ray of hope to close it before it’s too late.
In 2019, a group of scientists proposed a worldwide moratorium on human germline editing.
They wrote: ‘By ‘global moratorium’, we do not mean a permanent ban. Rather, we call for the establishment of an international framework in which nations, retaining the right to make their own decisions, voluntarily commit not to approve any use of clinical germline editing unless certain conditions are met.’
Late last year, Pfizer reported the death of a patient in its early-stage trial for a different gene therapy for Duchenne muscular dystrophy.
Meanwhile, in 1999, 18-year-old Jesse Gelsinger died during a study that involved placing healthy genes in his liver to combat a rare metabolic disease.
Scientists later learned that his immune system overreacted to the virus used to deliver the therapy.
The latest fatality related to CRISPR technology is likely to undermine public confidence that it is being used ethically and safely.
The sample size of the single-patient study was a sticking point for Dr. Caplan.
Horgan’s death ‘may make us wonder if we really like studies that are just about one person, and if we want to say, ‘No, ethically, you have to at least have a trial where you line up 5, 10, 20 people (and ) you learn from the data”.
Terry Horgan was diagnosed with DMD at age three. He loved computers as a child, once building his own, and playing ball in the driveway with his family when he could still walk, according to a release from Cure Rare Disease.
He used a motorized wheelchair later in his life. He studied data science at Cornell University and then worked at the school in the data science department.
Cure Rare Disease called Horgan “a medical pioneer whose courage and unwavering determination have paved the way for increased focus and attention on the funding and development of new therapies for patients with rare and ultra-rare diseases.”