Published January 13, 2015
This therapy involves injecting patients with a virus that has corrective genetic material added into its viral DNA core. It has been successful in treating head and neck cancer, correcting a severe form of immune deficiency in children and reviving dead heart tissue after a heart attack.
"These [results] are beginning to show the promise that can be realized for gene therapy if appropriate delivery vehicles are used," said Inder Verma, director of laboratory genetics at the Salk Institute and president of the American Society of Gene Therapy. "Gene therapy can influence nearly all aspects of human health in the coming century."
"The death of Jesse Gelsinger marked a turnaround," added Abbey Years, president of the National Organization of Rare Diseases, which advocates safe research on 6,000 serious genetic conditions. "The gene therapy field has really cleaned up its act quite a bit and we're finally beginning to see some success," she noted.
Gelsinger, an Arizona teenager who suffered from a genetic liver disease, volunteered for an experimental form of gene therapy at the University of Pennsylvania Institute for Human Gene Therapy. Researchers injected him with an adenovirus — a flu virus — into which they had spliced a segment of corrective genetic material. Although they said it might give him flu-like symptoms, they hoped it would "infect" Gelsinger's liver cells enough to counter their genetic defect.
But on September 16, 1999, Gelsinger died from a toxic reaction to the injection.
In the wake of his death, U.S. Government investigators closely scrutinized the study. They discovered that previous patients had suffered reactions, and that Gelsinger had not been notified. At the end of May this year, the University ordered the Institute to stop all human gene therapy experiments forever.
On Monday, Gelsinger's family filed a wrongful death suit against the University of Pennsylvania, accusing the University and the doctors and hospitals involved of minimizing the experiment's risks, Reuters reported Wednesday.
Meanwhile, the National Institutes of Health discovered other gene therapy researchers had failed to report 652 adverse events, many involving serious reactions to gene therapy experiments.
Since these discoveries, the FDA and NIH have reportedly started monitoring gene therapy experiments much more closely.
"There is more scrutiny now of the [treatment] protocols, and the training of personnel" in the gene therapy studies, said Verma. "But the increased scrutiny is justified."
The Brain Cancer Puzzle?
In the recent experiment involving head and neck cancer, researchers injected patients with the same virus that Gelsinger received, the ONYX-15 adenovirus. But the virus was modified differently, leading to less toxic results.
Instead of adding a human gene, the joint team of American and British researchers removed one of the viruses' own genes. This subtractive therapy caused the virus to attack cancer cells but not regular cells, the researchers reported in the August 2 issue of Nature Medicine.
The study results are particularly promising because head and neck cancers are difficult to surgically remove or kill with radiation without causing brain damage, according to the American Cancer Society. If the gene therapy can be injected instead, the cancer could potentially be treated more precisely and effectively.
Natural-Born Killer Cells
Children with a severe immune deficiency have also begun to benefit from gene therapy experiments.
This year, researchers at a Paris hospital treated these children, who had a severe genetic disease that made them unable to produce disease fighting white blood cells called T calls and natural killer lymphocytes, with genes that would correct this deficiency.
After ten months, two of the patients had fully functioning immune cells, the researchers reported in the April 28, 2000 issue of Science. The researchers traced the production of these cells to the genes they had injected in the patients.
Resurrecting Heart Tissue
A new heart disease study promises similar advances in treating this common killer.
In this study, scientists injected the gene for vascular endothelial growth factor (VEGF) into areas of dead heart tissue. The gene stimulated new blood vessel growth in these areas and increased blood flow to the heart, according to the study results published in the August 29 issue of Circulation, the Journal of the American Heart Association.
This therapy could one day be used to treat heart attack patients, the researchers said. In a heart attack, blood vessel blockage causes the heart tissue to be deprived of oxygen, and leads to rapid heart cell death. For some of the 13 patients in this study, the gene therapy revived areas of the heart that appeared to be dead.
Additionally, the patients experienced fewer angina attacks over a six month period, with the average number dropping from 48 per week to two per week, and their average use of nitroglycerin tablets — which treat angina attacks — decreased from 55 to two, the study reported.
This study came along with a big caveat: the treatment is still highly experimental and further studies are needed to confirm its safety and effectiveness, according to an accompanying editorial. But this qualification did not dampen the scientists' enthusiasm at their findings.
"There has been great concern about whether gene therapy works," said Dr. Jeffrey M. Isner of Tufts University School of Medicine, the study's lead author. "This is very solid evidence that it does."