August 6, 2019

'A very big deal': New study will use CRISPR to treat sickle cell disease

Daily Briefing

    Doctors are testing whether they can use CRISPR to treat patients with sickle cell disease, marking the first time doctors in the United States have used the gene-editing tool to treat a genetic disorder, NPR's "Shots" reports.

    Related: CRISPR—and 7 other technologies that could transform health care

    About sickle cell disease

    About 100,000 people in the United States have sickle cell disease. The disease mostly affects African Americans and results from a genetic defect that causes a patient's bone marrow to develop a defective protein that produces sickle-shaped blood cells. Because of their shape, the blood cells get stuck inside blood vessels and struggle to carry oxygen throughout the body, causing people who live with the disease to face a host of complications, including organ damage and infections.

    Victoria Gray, 34, was born with sickle cell disease, and has struggled with multiple sickle cell complications throughout her lifetime, including damage to her heart. "It's horrible," she said. "When you can't walk or lift up a spoon to feed yourself, it gets real hard."

    There is no cure for the disease, but some patients undergo bone marrow transplants as treatment. However, the transplants can be painful and cells from the transplanted bone marrow attack their bodies. It also can be difficult for patients to find a donor for the procedure.

    The 'landmark' study

    Gray was considering a bone marrow transplant when she came across a landmark trial testing whether CRISPR can be used to treat the genetic disease. She is the first patient to be publicly identified as involved in a study testing CRISPR as a way to treat a genetic disease, according to "Shots."

    For the study, doctors are extracting bone marrow cells from sickle cell patients' blood and using CRISPR to genetically modify the cells to make them produce fetal hemoglobin, a protein produced by fetuses in the womb to provide oxygen. The patients then undergo chemotherapy to kill the cells that carrying the defective protein. Once the patients are rid of those defective cells, doctors inject the CRISPR-modified bone marrow cells into the patient.

    The hope is that the fetal hemoglobin will make the blood cells "happier and healthier," Haydar Frangoul, medical director of pediatric hematology/oncology at the Sarah Cannon Research Institute in Nashville, said. And since the cells come from the patients' own bone marrow, Frangoul said they shouldn't attack the patients' bodies.

    The research is being conducted across eight sites in the United States, Canada, and Europe. The researchers hope to enroll up to 45 patients between the ages of 18 to 35.

    It will likely take the researchers months before they can tell whether the treatment is producing enough fetal hemoglobin and maybe years determine whether the treatment is causing any improvements in patients' health, "Shots" reports.

    "We don't really know how much fetal hemoglobin we need to treat a patient," said Vivien Sheehan, assistant professor of pediatrics and hematology at the Baylor College of Medicine, who is not involved with the trial. "That's why it's hard to know so early whether the edited cells from CRISPR will actually be effective."

    The risks vs. the benefits

    The treatment could be a safer alternative to a bone marrow transplant and could help patients who are struggling to find a bone marrow donor by allowing patients to be their own donor, according to Alexis Thompson, hematology section head at the Ann and Robert H. Lurie Children's Hospital of Chicago, who is not involved in the trial

    "This is a very big deal," Frangoul said. "This opens the door for many patients to potentially be treated and to have their disease modified to be mild."

    Laurie Zoloth, a bioethicist at the University of Chicago said the study could also pave the way for CRISPR being used to treat other genetic diseases. For instance, the method is also being tested to treat beta thalassemia, a genetic blood disorder where the body doesn't make enough hemoglobin.  "This is an exciting moment in medicine. CRISPR promises the capacity to alter the human genome and to begin to directly address genetic diseases," she said.

    But Zoloth is also concerned that the sickle cell study and other CRISPR studies haven't been subjected to enough scrutiny, adding that the method should be analyzed by a panel of experts through NIH.

    "This is a brand-new technology," she said. "It seems to work really well in animals and really well in culture dishes. It's completely unknown how it works in actual human beings. So there are a lot of unknowns. It might make you sicker."

    Frangoul said the study is being conducted under close review by FDA. "We are very cautious about how we do this trial in a very systematic way to monitor the patients carefully for any complications related to the therapy," he said.

    Patients like Gray, who were made aware of the risks, said the treatment was still "really hard and painful" at times, especially when the doctors transferred the edited cells into her body. But Gray said was relieved to have the "supercells" in her body. "This gives me hope if it gives me nothing else" (Stein, "Shots," NPR, 7/29; Nedelman/Nigam, CNN, 7/30).

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