orlando giri
In a landmark decision, the Food and Drug Administration on Friday approved the first gene-editing treatment to alleviate disease in humans.
The FDA has approved two gene therapies for people 12 and older who suffer from the most severe form of sickle cell disease, a brutal blood disorder that has long been ignored by medical research.
The decision is being hailed as a milestone for the treatment of sickle cell and the rapidly advancing field of gene editing, which is sparking excitement in the treatment of many diseases.
“Sickle cell disease is a rare, debilitating, and life-threatening blood disease with significant unmet need. Today, by approving two cell-based gene therapies, we are specifically We are excited to move this field forward for individuals whose lives are severely disrupted by cancer,” said Dr. Nicole Berdin, director of the Office of Therapeutic Products in the FDA's Center for Biologics Evaluation and Research, in a statement. mentioned in.
“Gene therapy has the potential to provide more targeted and effective treatments, especially for patients with rare diseases for whom current treatment options are limited.”
Jennifer Doudna of the University of California, Berkeley, who helped discover the gene-editing technology called CRISPR used in one of the sickle cell treatments, said: “I am overjoyed, excited and in awe.'' '' he said in an interview with NPR. “Today is an exciting day and the beginning of a new day in medicine.”
CRISPR therapy, developed by Boston-based Vertex Pharmaceuticals and CRISPR Therapeutics, allows doctors to remove cells from each patient's bone marrow, edit genes with CRISPR, and transfer billions of modified cells to the patient. Inject into.
The edited cells produce a type of hemoglobin known as fetal hemoglobin, which restores the normal function of red blood cells. Although there is no cure for this disease, hope is a cure. The brand name Kasugebi is designed to provide lifelong symptom relief with a one-time treatment.
According to data submitted to the FDA, this treatment resolved severe pain attacks for at least 18 months in 29 (96.7%) of the participants. This treatment has had similar results in patients suffering from a related disease known as beta-thalassemia.
The FDA has approved another gene therapy called Lifgenia, developed by Bluebird Bio. The research institute in Somerville, Massachusetts, is not using his CRISPR to treat sickle cell disease. Instead, Rifgenia uses a more traditional gene therapy that uses a virus to deliver genes into cells.
Treatment is expensive
But the excitement over the approval was tempered by concerns that many sickle cell patients would not have access to the breakthrough treatment.
Both are very expensive. Vertex said Kasgeby's wholesale price will be $2.2 million. Bluebird has set the wholesale price for Rifgenia at $3.1 million.
Treatment also requires complex and arduous procedures that many hospitals are not equipped to provide. Many patients may find treatment too physically and logistically difficult.
“There's still a lot of work to do” to make gene-editing treatments widely available, Berkeley's Doudna said.
Gene editing, which allows scientists to manipulate the fundamental building blocks of life more easily than ever before, is helping to transform everything from rare genetic diseases such as muscular dystrophy to common diseases such as cancer, heart disease, diabetes and AIDS. It is being researched as a treatment for a variety of illnesses. Alzheimer's disease.
Sickle cell disease is caused by a genetic defect that causes red blood cells to produce an abnormal form of the protein hemoglobin, which is needed to carry oxygen throughout the body. As a result, sickle cell patients have red blood cells that become misshapen and become stuck in blood vessels. It causes excruciating and unpredictable pain attacks, damages vital organs, and shortens the patient's life.
Sickle cell occurs disproportionately among people of African, Middle Eastern, and Indian descent, and affects millions of people worldwide and approximately 100,000 people in the United States. Although sickle cell is rare, it is one of the most common genetic disorders.
Although some patients can be cured by bone marrow transplantation, most patients are unable to find a suitable donor. Approximately 20,000 patients in the United States have severe forms of the disease that CRISPR therapy was originally planned to treat.
“I'm really excited,” Dr. Louis Hsu, a pediatric hematologist at the University of Illinois at Chicago and chief medical officer of the American Sickle Cell Association, said in an interview with NPR. “This is something we've been waiting for basically 70 years in the sickle cell community. This is a huge deal.”
life changed completely
The approval of CRISPR gene editing therapy was also welcomed by Victoria Gray of Forest, Mississippi, the first sickle cell patient in the United States to receive CRISPR gene editing therapy. NPR had exclusive access to document her experiences since she underwent treatment. 2019.
“I'm very happy. It's a blessing that this treatment has been approved. It's a new beginning for people with sickle cell disease,” Gray told NPR in a new interview.
Like many sickle cell patients, Gray was forced to rush to the hospital many times throughout his life for powerful painkillers and blood transfusions. She was often unable to finish school, keep her job, or even take care of herself or her children.
“This turned my life around. It gave me a new lease on life. It changed my life more than I could have imagined,” Gray says.
After treatment, Gray felt much better and was able to start selling cosmetics full time at Walmart, allowing her to spend more time with her four children, who are now teenagers. became.
“Since undergoing CRISPR treatment, I have had a new start. Best of all, I no longer have to fear leaving my children without a mother to die,” Gray says. “My life is limitless now. I'm full of energy. There's no pain. It's a real change.”
Technical complexity and prolonged hospitalization
Apart from the cost of treatment, another concern is that the procedure is long, difficult, and complex, requiring multiple visits to the hospital for tests, a grueling and potentially dangerous bone marrow transplant, and long hospital stays. That is to say. These factors could limit treatment from reaching those who need it most, not only in the United States but also in less affluent countries where the disease is most prevalent.
“I have mixed reactions,” says Melissa Cleary, an assistant professor at the University of Michigan who studies sickle cell at the University of Michigan School of Public Health and who has the disease herself. “We are excited about the promise this technology holds for people living with sickle cell disease. However, it will be very difficult to see how the benefits will outweigh social justice once this technology is brought to market.” It will be interesting.”
Many of the countries where many sickle cell patients live do not have enough advanced medical centers to provide complex treatment. Even in the United States, this treatment may not be widely available and is difficult to access.
“Patients in rural areas are likely at a disadvantage, and there may be entire states or regions that don't have gene therapy options,” Hsu said.
More gene editing treatments under research
Doudna leads a center in Berkeley that aims to make gene-editing treatments simpler and more accessible. The National Institutes of Health is also trying to address this issue.
The biotech company said it is working with private and public insurance companies to cover the procedure. Proponents point out that the higher costs of avoiding sickle cell complications for life can easily be offset.
Another concern is whether enough research has been conducted to detect “off-target” effects of treatments, or unintentional editing mistakes that can unmark DNA and cause long-term health problems. . The FDA warns that lifgenia, which uses more conventional gene therapy, may increase the risk of blood cancers.
The companies will follow all patients treated in the study for 15 years to determine whether and how effective the treatment actually helps patients live longer and monitor any signs of long-term complications. We'll see if it continues.
CRISPR-based therapies have also shown promise in treating a rare liver disease known as amyloidosis and an inherited form of hypercholesterolemia known as familial hypercholesterolemia.
“This is just the beginning,” says CRISPR researcher Doudna.