Gene-editing treatment shows promise for sickle cell disease
Scientists are seeing promising early results from the first studies testing gene editing for painful, inherited blood disorders that plague millionsworldwide.
Doctors hope the onetime treatment, which involves permanently altering DNA in blood cells with a tool called CRISPR, may treat and possibly cure sickle cell disease and beta thalassemia.
Partial results were presented Saturday at an American Society of Hematology conference and some were published by the New England Journal ofMedicine.
Doctors described 10 patients who are at least several months removed from their treatment. All no longer need regular blood transfusions and are free from pain crises that plagued their lives before.
Victoria Gray, the first patient in the sickle cell study, had long suffered severe pain bouts that often sent her to the hospital.
“I had aching pains, sharp pains, burning pains, you name it. That’s all I’ve knownmy entire life,” said Gray, 35, who lives in Forest, Mississippi. “I was hurting everywhere my blood flowed.”
Since her treatment a year ago, Gray has weaned herself from pain medications she depended on to manage her symptoms.
Sickle cell affects millions, mostly Black people. Beta thalassemia strikes about one in 100,000 people. The only cure nowis a bone marrow transplant from a closely matched donor without the disease like a sibling, which most people don’t have.
Both diseases involve mutations in a gene for hemoglobin, the substance in red blood cells that carries oxygen throughout the body.
In sickle cell, defective hemoglobin leads to deformed, crescent-shaped blood cells that don’t carry oxygenwell. They can stick together and clog small vessels, causing pain, organ damage and strokes.
Those with beta thalassemia don’t have enough normal hemoglobin, and suffer fromanemia, fatigue, shortness of breath and other symptoms. Severe cases require transfusions every two to fiveweeks.
The treatment studied attacks the problem at its genetic roots.
In the womb, fetuses make a special type of hemoglobin. After birth, when babies breathe on their own, a gene is activated that instructs cells to switch and make an adult form of hemoglobin instead. The adult hemoglobin is what’s defective in people with one of these diseases. The CRISPR editing aims to cut out the switching gene.
“What we are doing is turning that switch back off and making the cells think they are back in utero, basically,” so they make fetal hemoglobin again, said one study leader, Dr. Haydar Frangoul of the SarahCannonResearch Institute inNashville.
The treatment involves removing stem cells from the patient’s blood, then using CRISPR in a lab to
knock out the switching gene. Patients are given strong medicines to kill off their other, flawed bloodproducing cells. Then they are given back their own lab-altered stem cells.
Saturday’s results were on the first 10 patients, seven with beta thalassemia and three with sickle cell. The two studies in Europe and the United States are ongoing and will enroll 45 patients each.
Tests so far suggest the gene editing is working as desired with no unintended effects, Frangoul said.
The study was sponsored by the therapy’s makers — CRISPR Therapeutics, with headquarters in Zug, Switzerland, and Massachusetts-based Vertex Pharmaceuticals. Some study leaders consult for the companies.
Separately, Dr. David Williams of Harvard-affiliated Boston Children’s Hospital gave partial results from a study testing a novel type of gene therapy that also seeks to restore fetal hemoglobin production for those with sickle cell.
Six patients, including one as young as 7, were given the treatment, in which some of their blood stem cells were removed and altered in the lab to muffle the hemoglobin switching gene.