Gene-editing treatment has promise for sickle cell
Scientists are seeing promising early results fromthe first studies testing gene editing for painful, inherited blood disorders that plaguemillions worldwide.
Doctors hope the one-time treatment, which involves permanently altering DNA in blood cells with a tool called CRISPR, maytreat 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 EnglandJournal ofMedicine.
Doctors described 10 patients who are at least several months removed fromtheir treatment. All no longer need regular blood transfusions and are free frompaincrises 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. “Iwas hurting everywhere my blood flowed.”
Since her treatment a year ago, Gray has weaned herself from painmedications she depended on to manage her symptoms.
“It’s something I prayed for my whole life,” she said. “I pray everyone has the same results I did.”
Sickle cell affects millions, mostly Black people. Beta thalassemia strikes about one in 100,000 people. The only cure now is a bone marrow transplant from a closely matched donorwithout 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 oxygen well. 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 anemia, fatigue, shortness of breath and other symptoms. Severe cases require transfusions every two to fifive weeks.
The treatment studied attacks the problem at its genetic roots.
Inthewomb, fetusesmake a special type of hemoglobin. After birth, whenbabies breathe on theirown, a gene is activated that instructs cells to switch and make an adult form of hemoglobin instead. The adult hemoglobin iswhat’s defective in peoplewith one of these diseases. The CRISPR editing aims to cut out the switching gene.
“What we are doing is turning that switch back offff 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 Sarah Cannon Research Institute in Nashville.
The treatment involves removing stemcells fromthe patient’s blood, then using CRISPR in a lab to knock out the switching gene. Patients are given strongmedicines to kill off their other, flawed blood- producing cells. Then they are given back their own lab-altered stem cells.
Saturday’s results were on the first 10 patients, sevenwith 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 desiredwith no unintended effects, Frangoul said.
“The preliminary results are extremely encouraging,” he 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.