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Victoria Gray patiently waits in a hospital room at the Sarah Cannon Research Institute in Nashville.
"It's a good time to be healed," she says. The 34-year-old from Forest, Miss., Has been struggling with sickle cell disease throughout her life.
Gray is in hospital because she volunteered for one of the most anticipated medical experiments for decades: the first attempt to use the gene-editing technique CRISPR to treat a genetic disorder in the US
is the first female patient to be publicly considered to be involved in such a study.
"I always hoped something would happen," says Gray in an exclusive interview with NPR. "It's just amazing how far things have progressed, I just want to help make this disease known and let others know there's hope."
Sickle cells affect millions of people around the world. About 100,000 are in the US and most of them, like Gray, are African Americans. A genetic defect causes the bone marrow to produce a defective protein that causes crescent, hard, and sticky blood cells. The deformed cells remain stuck in blood vessels and normally do not carry oxygen, resulting in a variety of debilitating and often life-shortening complications.
"It's awful," says Gray. "If you can not walk or lift a spoon to feed yourself, it will be very difficult."
For the study, physicians use cells from the patient's own bone marrow that are genetically inherited using CRISPR to produce a protein that is normally only produced by fetuses and babies for a short time after birth will be produced.
The hope is this protein will compensate for the defective protein that causes sickle cell disease, and allow patients a normal life for the rest of their lives.
"It is exciting to see that we are on the threshold of a highly effective therapy for sickle cell patients," says Dr. David Altshuler, Executive Vice President, Global Research and Chief Scientific Officer of Vertex Pharmaceuticals in Boston. Vertex is co-sponsoring the study with CRISPR Therapeutics of Cambridge, Massachusetts.
"People with sickle cell disease have long been waiting for therapies that could lead them to a normal life," says Altshuler.
"This is a very big deal," agrees Dr. Haydar Frangoul to, Medical Director of Pediatric Hematology / Oncology at the Institute where Gray volunteered. "This could benefit many patients."
Frangoul's Center, Sarah Cannon, is conducting the study at HCA Healthcare's TriStar Centennial Medical Center in Nashville, one of eight centers recruiting patients for research in the US, Canada and Europe. Up to 45 patients aged 18 to 35 years are eventually included.
Other doctors, scientists and bioethicists are also encouraged.
"This is an exciting moment in medicine, and CRISPR promises the ability to change the human genome and start addressing genetic diseases directly," says Laurie Zoloth, a bioethicist at the University of Chicago.
Zoloth, however, is also careful. She fears that these and other studies that began with CRISPR have not been reviewed by a panel of external experts compiled by the National Institutes of Health.
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"This is a brand new technology," says Zoloth. "It seems to work very well with animals and very well with culture dishes, it's completely unknown how it works in actual humans, so there are a lot of unknowns, it could make you sick."
Frangoul admits that there are always risks in experimental treatments. He says, however, that the research will be reviewed very slowly and carefully by the Food and Drug Administration and other advisory bodies.
"We are very cautious on how to do this study in a very systematic way to monitor the patients. Be wary of complications related to the therapy," he says.
Gray says there are risks. She also says that she knows the study is a first step and that other patients may not see any benefits for years.
"This gives me hope, if there is nothing else," says Gray.
It's likely to take several months before doctors see the first signs that the genetically engineered cells are producing useful amounts of the protein, and even longer, to see if the cells improve patient health. And it will probably take many years before we know if the benefits are expected to last a lifetime.
Gray, a married man and father of four, was diagnosed with sickle cell disease as an infant and started crying during a bath. A major symptom is agonizing, debilitating pain.
Like many sickle cell patients, their symptoms have prevented them from living a full life. She could not play like other children, was afraid of travel and had to give up her dream of becoming a doctor or nurse.
Meredith Rizzo / NPR
"Sometimes it feels like a lightning bolt in my chest and real, sharp pain," says Gray. "Sometimes I just crumple up and cry and can not do anything for myself."
Defective blood cells also increase the risk of infection and damage to vital organs such as the heart. They can also cause life-threatening strokes. Many people with sickle cell disease do not live older than 40 years. Gray's heart has already suffered damage. And that costs an additional psychological tribute.
"It's scary," she describes how her illness affected her eldest son, 12-year-old Jamarius.
"He's older, so he understands, so he does." started playing at school. And his teacher said to me, "I think Jamarius is playing because he really believes you're going to die," says Gray, choking back tears.
Some patients may get bone marrow transplants. However, these procedures are strenuous and can be dangerous if the cells of the immune system produced by the transplanted bone marrow attack their body. And most sickle cell patients do not have or find a suitable donor.
"It's very hard," says Gray. "It was just my religion that kept me going."
When she was thinking about a bone marrow transplant, she heard about the CRISPR study and took the opportunity to volunteer.
"I always knew something had to come and that God had something important in store for me," says Gray, "it felt like it was meant to be. It was a destiny. That was an amazing feeling. "
CRISPR enables scientists to make very precise changes to DNA, and raises hopes that it will lead to new ways to prevent and treat many diseases.
Doctors have already begun to treat cancer, especially in China. At least two patients in the US were treated for cancer in a study at the University of Pennsylvania in Philadelphia.
Later that year, Boston physicians plan to use CRISPR to treat cells in the retina of patients, hoping to restore vision in hereditary blind patients.
The companies that funded the Sickle Cell Study announced earlier this year that they had used CRISPR to treat the first patient with a similar blood disorder, beta-thalassemia, in Germany.
Beta-thalassemia and sickle cell disease are both genetically caused defects that cause problems with a protein called hemoglobin. Healthy red blood cells transport oxygen through the body with hemoglobin.
The red cells of sickle cell patients carry defective hemoglobin, which deforms the cells and does not carry enough oxygen. The hope is that another form of hemoglobin, called fetal hemoglobin, compensates for the defective protein.
Fetal hemoglobin is produced by fetuses in the womb to provide oxygen. In most people, fetal hemoglobin production ceases shortly after birth.
"Once a baby is born, a switch turns on," says Frangoul. "It's a gene that instructs the red blood cells – the bone marrow cells that produce red blood cells – to stop producing fetal hemoglobin."
This CRISPR treatment begins with doctors extracting bone marrow cells from the patient's blood. The company's scientists then use CRISPR to process a gene in the cells for the cells to produce fetal hemoglobin. "This will help the cells produce more fetal hemoglobin and make them happier and healthier," says Frangoul.
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Patients then receive the same strenuous chemotherapy that is given as part of a standard bone marrow transplant. This erases the existing cells that carry the genetic defect. Instead of receiving new cells from a donor, patients receive billions of their own cells that have been processed with CRISPR.
The hope is that it offers a treatment option for all patients, even those who can. & # 39; Find a suitable donor. Hopefully, the approach will be safer because the cells come from the patient's bone marrow. So you should not attack patients' bodies, says Frangoul.
"This opens the door for many patients to potentially be treated and mildly modify their disease" and to avoid the "terrible, terrible long-term side effects of sickle cell disease," he says.
Gray hopes it will work and describes how she envisioned a life without sickle cells:
"Being able to wake up and not have pain has done something – and not just groundless tiredness – and only to be outside and jump on the trampoline with my children.
"And to go to graduation parties and weddings. And see how they grow up. That means the world to me. "