JUL 05, 2020 4:48 AM PDT

Two Deaths Occur During Gene Therapy Trial

WRITTEN BY: Carmen Leitch

There is great promise, as well as serious risks in gene therapy. Many diseases can be traced back to an error or mutation in the sequence of the genome, and sometimes those errors are very small. If a disease-causing genetic mutation can simply be corrected, which is easier said than done, many genetic diseases could be cured. Scientists have been trying to find ways to not only create a genetic template that can be used to correct mutations, but also a delivery system that can take gene therapy to the nucleus of a cell, where the genome is.

One recent trial of a gene therapy called AT132 was meant to treat X-linked myotubular myopathy, a rare neuromuscular disorder. Like many gene therapies, it is delivered with what was engineered to be a non-pathogenic virus called adeno-associated virus 8 (AAV8). Early tests of the therapy had been promising. In the case of a neuromuscular disease, the treatment must enter the bloodstream, which can dilute it before it reaches its target, thus requiring high doses. That's where problems seem to have arisen.

Now, two children in a clinical trial have died after they got a high dose of the AT132 gene therapy. In both cases, liver problems started and led to sepsis. While the company conducting the trials, Audentes, meant to submit applications to approve the treatment this year, those plans have been halted.

Image credit: Max Pixel

Though there are some approved gene therapies, researchers that have spent years in the field have cautioned against using high doses.

Jim Wilson led a pioneering gene therapy trial at The University of Pennsylvania about two decades ago. He and colleagues were concerned enough about high doses that they published a recent report about their concerns in the journal Human Gene Therapy, which noted that liver and nerve damage happened in animals that received some kinds of gene therapy.

Audentes reported on May 6 that high doses of AT132 had caused death due to sepsis in two patients, and two others were experiencing serious side effects. On June 23, the company reported that one of the two people experiencing side effects had also died due to progressive liver dysfunction and sepsis due to bacterial infection. These patients had also come into the study with pre-existing liver problems.

"There have been some incredible outcome measures with some of the children but the science needs to continue to evolve," said Alison Rockett Frase, president of the Joshua Frase Foundation, one of the patient groups Audentes wrote. "Our community is devastated by the loss of these two children," she added in an interview.

There are 17 other patients that are still being monitored after getting high doses of AT132. Six patients that received a low dose were not experiencing problems, even years after the treatment.

Sources: Joshua Frase Foundation/Audentes, Biopharma Dive

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
MAY 13, 2021
Genetics & Genomics
Explore Ways to Enhance Biomarker Discovery Research
MAY 13, 2021
Explore Ways to Enhance Biomarker Discovery Research
Enhance your existing research or discover new methods with a suite of NGS tools and techniques to find and characterize ...
MAY 20, 2021
Genetics & Genomics
Mitochondrial DNA May be Affecting More Traits Than we Knew
MAY 20, 2021
Mitochondrial DNA May be Affecting More Traits Than we Knew
While the vast majority of our genes are in the genome that's held in the nuclei of cells, mitochondria are also known t ...
MAY 27, 2021
Neuroscience
Research Less Likely to Be True is Cited More
MAY 27, 2021
Research Less Likely to Be True is Cited More
Researchers from the University of California San Diego have found that non-replicable data is cited 153 times more ofte ...
JUN 06, 2021
Cell & Molecular Biology
Caught in the Act of RNA Transcription
JUN 06, 2021
Caught in the Act of RNA Transcription
Researchers have now been able to capture an enzyme called RNA polymerase on video as it copies a DNA sequence into an R ...
JUN 23, 2021
Genetics & Genomics
Expansive RNA Atlas Includes Coding & Non-Coding Molecules
JUN 23, 2021
Expansive RNA Atlas Includes Coding & Non-Coding Molecules
We'e sequenced the human genome, even the parts that are highly repetitive, don't code for protein, and are extremely ch ...
JUL 18, 2021
Cannabis Sciences
Genetic Analysis Reveals Cannabis First Grown in China
JUL 18, 2021
Genetic Analysis Reveals Cannabis First Grown in China
Genetic analysis of over 100 cannabis Sativa genomes has revealed that the plants’ wild ancestors likely came from ...
Loading Comments...