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The lone volunteer in a trial to test an experimental and controversial gene editing therapy has died of unknown causes.
Terry Horgan, of Montour Falls, New York, took part in the study in late August hoping to treat 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 produce a protein called dystrophin.
At this time, Horgan’s exact cause of death last month remains unclear.
But his death raises questions about the general prospect of gene editing therapies, which have sparked hope in many families dealing with rare and incurable diseases.
At this point, it’s unclear whether Horgan received the treatment and whether CRISPR, other aspects of the investigation, or the disease itself contributed to his death.
Deaths are not unheard of in clinical trials, testing experimental treatments and sometimes involving very sick people.
But trials of CRISPR are relatively new. And Fyodor Urnov, a CRISPR expert at the Innovative Genomics Institute at the University of California, Berkeley, said any death during a gene therapy trial is an opportunity for the field to settle.
“Step one is mourning the passing of a brave human soul who agreed to essentially participate in an experiment on a human,” Urnov said. “But then, as far as we can, we have to learn as much as we can to find a way forward.”
Terry Horgan, 27, died last month while participating in a trial for a new gene-editing technology aimed at treating his Duchenne muscular dystrophy, a fatal genetic condition that causes muscle deterioration.
CRISPR is a way of finding a specific strand of DNA in a cell and then removing, adding, or altering parts 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 approximately 20,000 children each year. the disorder occurs in one in 3,500 to 5,000 newborns worldwide.
The condition is caused by a mutation on the X chromosome that causes problems with the production of the protein dystrophin, which helps strengthen muscle cells and keep them intact.
Deficiency of dystrophin causes a person’s muscle fibers to break down when exposed to enzymes in the body, causing them to lose the strength needed to perform daily tasks.
The condition occurs mainly in males and is usually diagnosed early between the ages of two and six.
DMD is usually treated with a corticosteroid, which slows disease progression.
The introduction of corticosteroids can alter the levels of the hormone testosterone. This can lead to delayed puberty.
Many DMD patients die in their teens. However, medical advances in healthcare in recent years have extended the lifespan of many patients into their thirties, forties and fifties.
Cure Rare Disease, which funded the study and was founded by Horgan’s brother, said in a statement: “The loss of Terry is heartbreaking and he will be remembered as a hero.”
Cure Rare Disease said multiple research teams in the US are assessing Horgan’s probable cause of death, adding, “This is a complex undertaking that 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 results of the study, but also “on the challenges of gene therapy in general.” ‘.
The investigators provided a report of the incident 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 both praised and slammed since it was first unveiled 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 that gene-editing technology could one day help cure cancer or HIV patients, allowing doctors to repair defective 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 cancers and neurodegenerative disorders.
Despite its promise, CRISPR is not perfect.
dr. Arthur Caplan, medical ethicist at New York University, told Associated Press: ‘We know that CRISPR can miss its mark. We know that CRISPR can be partially effective. And we also know that there can be problems with … viral vectors that deliver the therapy into the body.”
Safety concerns in gene editing technology research are not unheard of.
There is a risk of accidentally altering the DNA or RNA in regions other than the target site, which could lead to unwanted side effects. For example, inadvertent alteration of a tumor suppressor gene can lead to cancer.
A major scandal shook the world in 2019 when Chinese scientist He Jiankui was imprisoned after modifying the DNA of twin girls Lulu and Nana to make them resistant to HIV before birth.
His work to manipulate the genes of human embryos was considered “monstrous”, “unethical” and “very dangerous”.
A group of more than 100 scientists in China denounced He’s work in 2018: “Performing direct human experiments can only be described as crazy.”
The group added: “Pandora’s box has been opened. We may still have a glimmer of hope to close it before it’s too late.’
In 2019, a group of scientists proposed a global moratorium on human germline editing.
They wrote: ‘By ‘global moratorium’ we do not mean a permanent ban. Rather, we advocate the creation of an international framework in which countries, while retaining the right to make their own decisions, voluntarily commit not to approve the use of clinical germline editing unless certain conditions are met.”
Late last year, Pfizer reported the death of an early-stage patient of a trial for another gene therapy for Duchenne muscular dystrophy.
In 1999, 18-year-old Jesse Gelsinger died during a study that placed healthy genes in his liver to fight a rare metabolic disease.
Scientists later found 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 in an ethical, safe manner.
The sample size of the study of only a single patient was a sticking point for Dr. Caplan.
Horgan’s death ‘may make us think about whether we like studies that are just on one person, and would we say, ‘No, ethically you should at least have a trial where you have 5, 10, 20 people (and) you learns from the data.”
Terry Horgan was diagnosed with DMD at the age of three. As a child, he was fond of computers — having once built his own — and playing in the driveway with his family when he could still walk, according to a statement from Cure Rare Disease.
Later in life, he used a motorized wheelchair. He studied computer science at Cornell University and then went on to work at the school in the information science department.
Cure Rare Disease called Horgan “a medical pioneer whose courage and unwavering determination have paved the way for increased focus and focus on funding and developing new therapies for patients with rare and extremely rare diseases.”