Scientists are seeing promising early results from the first studies to examine the effects of gene editing on painful, inherited blood disorders that plague millions worldwide, especially black people.
Doctors hope the one-time 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 at an American Society of Haematology conference, and some were published by the New England Journal of Medicine.
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 that had plagued their lives before.
Victoria Gray, the first patient in the sickle cell study, was a lifelong sufferer of severe pain bouts that often sent her to hospital.
“I had aching pains, sharp pains, burning pains, you name it. That’s all I’ve known my entire life,” said Ms Gray, 35, who lives in Forest, Mississippi. “I was hurting everywhere my blood flowed.”
Since her treatment a year ago, Ms Gray has weaned herself from pain medication 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 for now is a bone marrow transplant from a closely matched donor without the disease, such as a sibling.
Both diseases involve mutations in a gene for haemoglobin, the substance in red blood cells that carries oxygen throughout the body.
In sickle cell, defective haemoglobin leads to deformed, crescent-shaped blood cells that do not carry oxygen well. They can stick together and clog small vessels, causing pain, organ damage and strokes.
Those with beta thalassemia do not have enough normal haemoglobin, and suffer anaemia, fatigue, shortness of breath and other symptoms. Severe cases require transfusions every two to five weeks.
The treatment being studied attacks the problem at its genetic roots.
In the womb, foetuses make a special type of haemoglobin.
After birth, when babies breathe on their own, a gene is activated that instructs cells to switch and make an adult form of haemoglobin instead. The adult haemoglobin is what is defective in people with one of these diseases.
The CRISPR editing aims to cut out the switching gene.
One leader of the study, Dr Haydar Frangoul of the Sarah Cannon Research Institute in Nashville, said: “What we are doing is turning that switch back off and making the cells think they are back in utero, basically”. This means that they make foetal haemoglobin again.
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 blood-producing 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 enrol 45 patients each.
Tests so far suggest the gene editing is working as desired with no unintended effects, Dr Frangoul said.
“The preliminary results are extremely encouraging,” he added.
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 the Harvard-affiliated Boston Children’s Hospital gave partial results from a study testing a novel type of gene therapy that also seeks to restore foetal haemoglobin production for those with sickle cell.
Six patients including one as young as seven, were given the treatment, in which some of their blood stem cells were removed and altered in the lab to muffle the haemoglobin switching gene.
None have had pain crises, five of the six no longer need transfusions and all have near-normal haemoglobin, he reported at the conference and in the medical journal.
Government grants paid for the work.
Dr Williams is named on a patent for the therapy, which Boston Children’s has licensed to Bluebird Bio of Cambridge, Massachusetts. The company provided the therapy for the study, which will enrol 10 people in all to establish safety. A larger study to test the treatment’s effectiveness is planned.
Dr Williams, who was not involved in Dr Frangoul’s study, said it “validates this approach” of targeting the haemoglobin switching gene to tackle sickle cell.