CRISPR Eliminated Symptoms of Genetic Disease in 2 Patients

But it’s too soon to know if it’s a cure

Credit: Janice Haney Carr, Sickle Cell Foundation of Georgia and Jackie George, Beverly Sinclair, USCDCP

Victoria Gray was used to the attacks of excruciating pain. They came regularly, more than a half-dozen times per year, and were a side effect of her sickle cell disease. But since receiving a revolutionary new gene-editing treatment in July that uses CRISPR, Gray has yet to have one of these painful episodes.

On Tuesday, CRISPR Therapeutics and Vertex Pharmaceuticals, the companies that are developing the experimental therapy, announced that Gray, as well as another patient suffering from a related genetic disorder called beta thalassemia, now appear to be free of disease symptoms after receiving the treatment.

The news comes on the heels of another report of CRISPR being used to treat three patients with advanced cancers. CRISPR has spurred hope that it could be a one-shot treatment — or possibly even a cure — for a wide range of diseases. And now scientists are putting that notion to the test in the first human experiments of the gene-editing technique.

Sickle cell anemia and beta thalassemia affect millions of patients around the world. Both diseases arise from mutations in the HBB gene, which provides instructions for making hemoglobin, a critical protein in the blood that helps transport oxygen throughout the body. In sickle cell disease, malfunctioning hemoglobin makes misshapen red blood cells that look like sickles — hence the name. In beta thalassemia, the body simply doesn’t make enough hemoglobin. Complications from the two diseases, like organ damage, can result in early death.

But the experimental treatment that Gray received at a Nashville hospital could change that. On Tuesday, CRISPR Therapeutics CEO Samarth Kulkarni told investors in a conference call that the companies’ experimental treatment “has the potential to be a curative approach” for patients with sickle cell disease and beta thalassemia.

To treat these diseases, scientists at the companies made a single genetic edit in patients’ cells. Doing so first involves withdrawing blood from patients, then isolating the blood-producing stem cells. Next, using CRISPR, scientists edit the diseased cells in the lab and then infuse the modified cells back into the bloodstream. The idea is that the edited stem cells will give rise to a population of healthy blood cells, enough to eliminate a patient’s symptoms. And so far, the approach seems to be working.

The bouts of pain that Gray experienced are a hallmark of sickle cell anemia, caused by misshapen hemoglobin sticking together and blocking the flow of oxygen in the blood vessels. Since receiving the CRISPR therapy, which created cells that produced a healthy version of hemoglobin, she has been pain-free. (NPR has had exclusive access to document Gray’s treatment.)

The beta thalassemia patient, who was treated in Germany and hasn’t been publicly identified, is also faring well, according to the companies. Before getting the treatment, the patient needed 16 blood transfusions a year, which is typical for people with the condition. Beta thalassemia patients often require regular blood transfusions every two to five weeks throughout their lifetimes to supplement their blood with the hemoglobin that their own blood naturally lacks. But the companies report that the patient in the trial has not needed a transfusion in the nine months since receiving the CRISPR-edited cells. Both patients experienced some temporary but treatable side effects that were not considered related to the CRISPR therapy.

“It bodes well for the technology moving forward.”

The single genetic edit the scientists made to both patients’ cells was meant to switch on production of fetal hemoglobin, a protein that can substitute for the diseased hemoglobin. Fetal hemoglobin is made by human fetuses but production normally turns off after birth. In rare cases, some people continue to make fetal hemoglobin into adulthood, which shields them from the effects of sickle cell and beta thalassemia. Using CRISPR, the scientists hope to mimic this protective ability.

“This approach is supported by decades of human genetic studies of rare patients who have naturally high levels of fetal hemoglobin and are protected from disease symptoms without any harmful side effects,” explained Dr. Tony Ho, head of research and development for CRISPR Therapeutics, on the conference call.

Scientists think if they can make 25% to 30% of a patient’s total blood cells produce fetal hemoglobin, it would be enough to essentially cure sickle cell. Gray’s fetal hemoglobin levels, according to the companies, are close to 47%.

To know whether the treatment actually represents a permanent cure, researchers will need to test it in many more patients and follow their progress for years. CRISPR Therapeutics and Vertex already plan to enroll 45 sickle cell patients and another 45 with beta thalassemia in its two clinical trials.

If the cure proves successful, cost and accessibility will be the next challenge. Gene therapies that don’t use CRISPR have come with multimillion-dollar price tags. Some sickle cell and beta thalassemia patients have already been cured with bone marrow transplants, also known as stem cell transplants, but the procedure can cost anywhere from $100,000 to $300,000 and can have side effects, such as inflammation and infection — and that’s assuming patients can find rare matching donors.

“It bodes well for the technology moving forward,” Jennifer Doudna, a co-inventor of CRISPR and biochemist at the University of California, Berkeley, told OneZero about the early trial results. Doudna is a co-founder of several CRISPR companies but is not involved in CRISPR Therapeutics or Vertex. “Obviously, this was just in two patients and there’s a lot more work that needs to be done, but I think this is an exciting development in the field for sure.”

Former staff writer at Medium, where I covered biotech, genetics, and Covid-19 for OneZero, Future Human, Elemental, and the Coronavirus Blog.

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