U.S. health officials are eliminating special regulations for gene therapy experiments, saying that what was once exotic science is quickly becoming an established form of medical care with no extraordinary risks.
A special National Institutes of Health oversight panel will no longer review all gene therapy applications and will instead take on a broader advisory role, according to changes proposed Wednesday. The Food and Drug Administration will vet gene therapy experiments and products as it does with other treatments and drugs.
It’s an extraordinary milestone for a field that has produced only a few approved treatments so far, and not all experts agree that it doesn’t still need special precautions.
With gene editing and other frontiers looming, “this is not the right time to be making any moves based on the idea that we know what the risks are,” said Stanford bioethicist Mildred Cho.
Gene therapy aims to attack the root cause of a problem by deleting, adding or altering DNA, the chemical code of life, rather than just treating symptoms that result from a genetic flaw.
What is gene therapy?
Gene therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery. Researchers are testing several approaches to gene therapy, including:
- Replacing a mutated gene that causes disease with a healthy copy of the gene.
- Inactivating, or “knocking out,” a mutated gene that is functioning improperly.
- Introducing a new gene into the body to help fight a disease.
Source: NIH
- Additional information: Read more about gene therapy at a special NIH website.
Although gene therapy is a promising treatment option for a number of diseases (including inherited disorders, some types of cancer, and certain viral infections), the technique remains risky and is still under study to make sure that it will be safe and effective. Gene therapy is currently being tested only for diseases that have no other cures.
When it was first proposed, there were so many safety worries and scientific unknowns that the NIH created a panel of independent scientists, called the Recombinant DNA Advisory Committee, or RAC, to assess each experiment and potential risks to patients. The risks were underscored in 1999, when a teen’s death in a gene experiment put a chill on the field.
Since then, much has been learned about safety, and last year the FDA approved the nation’s first gene therapies, for cancer and an inherited form of blindness.
It’s time to let the FDA review gene therapy proposals on its own without duplicating regulatory efforts, the NIH’s director, Dr. Francis Collins, and FDA chief Dr. Scott Gottlieb wrote Wednesday in the New England Journal of Medicine. The proposed changes will go into effect after a public comment period.
More than 700 proposals for gene therapy are pending now, and “it seems reasonable to envision a day when gene therapy will be a mainstay of treatment for many diseases,” they wrote. “The tools we use to address other areas of science are now well suited to gene therapy.”
Gene therapy research in the Triangle
Gene therapy is a hot research topic across the Triangle, which is one of the nation’s largest life science hubs. Three recent developments:
Several independent experts agreed.
“This is something the FDA has the tools to handle. I don’t think this is somehow a massive deregulation,” said Leigh Turner of the University of Minnesota Center for Bioethics. “We never want to become blase or cavalier about gene therapy clinical trials. Careful scrutiny, whether by one body or two, is as important as ever.”
Jeffrey Kahn, director of the Bioethics Institute at Johns Hopkins University, said the move is consistent with recommendations from the Institute of Medicine several years ago.
“We have mechanisms in place to protect patients,” he said. “It doesn’t need to be treated as a special case of clinical research any longer.”
But Cho, who is a member of the RAC, said gene therapies are biologically complex treatments, and “we really don’t understand how they work,” in many cases. “There are miraculous recoveries and remissions that we haven’t seen before but there also are very spectacular failures.”
Important caveat: The rules in question govern gene therapies that alter DNA to treat diseases after someone is born — not altering embryos, eggs or sperm to make permanent changes that would be passed down through generations. That’s prohibited under current rules.
“We need to strengthen rather than weaken the review apparatus if the FDA were to start to consider proposals” for that, said Marcy Darnovsky, executive director of the Center for Genetics and Society, a group that advocates for oversight and responsible use of biotechnologies.
How does gene therapy work?
Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. If a mutated gene causes a necessary protein to be faulty or missing, gene therapy may be able to introduce a normal copy of the gene to restore the function of the protein.
A gene that is inserted directly into a cell usually does not function. Instead, a carrier called a vector is genetically engineered to deliver the gene. Certain viruses are often used as vectors because they can deliver the new gene by infecting the cell. The viruses are modified so they can’t cause disease when used in people. Some types of virus, such as retroviruses, integrate their genetic material (including the new gene) into a chromosome in the human cell. Other viruses, such as adenoviruses, introduce their DNA into the nucleus of the cell, but the DNA is not integrated into a chromosome.
The vector can be injected or given intravenously (by IV) directly into a specific tissue in the body, where it is taken up by individual cells. Alternately, a sample of the patient’s cells can be removed and exposed to the vector in a laboratory setting. The cells containing the vector are then returned to the patient. If the treatment is successful, the new gene delivered by the vector will make a functioning protein.
Researchers must overcome many technical challenges before gene therapy will be a practical approach to treating disease. For example, scientists must find better ways to deliver genes and target them to particular cells. They must also ensure that new genes are precisely controlled by the body.
Source: NIH
