Base editing, a new form of gene therapy, leaves patient feeling ‘more than fine’

Though he doesn’t remember it, Branden Baptiste had his first sickle cell crisis at age 2. Through elementary school, he was in and out of the hospital with pain episodes, not knowing why. As he got older, he learned he had sickle cell disease. His red blood cells were forming sickle shapes and getting stuck in his blood stream, preventing oxygen from reaching his tissues.

“Sickle cell disease has a broad spectrum of severity, and the severity and frequency of complications can wax and wane,” says Matthew Heeney, MD, Branden’s long-time hematologist at Boston Children’s Hospital.

“Unfortunately, Branden was quickly acquiring many of the chronic complications of sickle cell disease, including organ dysfunction affecting his kidneys, lungs, joints, and eyes.”

Choosing base editing gene therapy

Around that time, potentially curative gene therapies for sickle cell disease were becoming available. Heeney, then director of Boston Children’s Sickle Cell Disease Program, offered Branden two options. One, a clinical trial called GRASP, would treat his cells with a virus carrying instructions for his red blood cells to make a fetal form of hemoglobin. (Unlike “adult” hemoglobin, fetal hemoglobin doesn’t cause sickling.)

But a new trial called BEACON, led at Boston Children’s by Heeney, could enroll Branden immediately. The trial is testing base editing—the most precise form of gene therapy yet developed—as a way to boost fetal hemoglobin production.

In contrast to conventional gene editing strategies that create a cut or break in the double strand of DNA, base editing uses enzymes to correct a single misspelled “letter” of a gene.

Branden would be the first person in the world to receive base editing for sickle cell disease, and among the first to receive this method of gene therapy for any condition.

Branden agreed to take the gamble. His symptoms, especially ACS, had become unbearable. He wanted them gone so he could get on with life.

A journey with many steps

Over the course of 2023, Branden came to Boston Children’s for a series of tests to ensure he could withstand the rigors of gene therapy treatment. By October 2023, he was ready. The first step was to collect blood stem cells from his blood, which required Branden to stay at Boston Children’s for several days, on two occasions. The precious stem cells were then delivered to a special facility to undergo base editing treatment.

But before Branden could receive his base-edited cells, he needed chemotherapy to kill off the diseased blood stem cells in his bone marrow and make room for the treated cells. He was readmitted to Boston Children’s in late November 2023, and was finally infused with his genetically treated cells on December 5.

A change in a single DNA base (A, C, T, or G) could be enough to cure Branden’s sickle cell disease.

The next step was to wait for the treated cells to settle into Branden’s bone marrow and start producing blood cells. This kept him in the hospital for several more weeks.

“I was fine. I was bored,” Branden says. “I was waiting for my blood to build back.”

‘I’m operating in every way possible’

Branden surprised and delighted his family by arriving home on Christmas Eve—well ahead of schedule.

“Everyone was like, ‘What?'” he says. “Initially, I was told I would be in the hospital for two months, and then I got out in 20 days. Everyone was shocked, even the doctors were shocked.”

Branden has felt good ever since his infusion and says he’s off all his sickle cell medication. “In my opinion, I’m perfect. I never felt fine before—before, ‘fine’ was moderate pain. I could take deep breaths through. Now I’m more than fine. I’m operating in every way possible.”

Another big change in Branden’s life: he can now exercise. “I used to always try to exercise, but every little movement would cause joint pain, and exhaustion would also cause pain,” he says. “Now I’m going to the gym every day, doing cardio and weight lifting.”

Branden will be monitored closely by Boston Children’s Gene Therapy Program for the next 15 years. The BEACON trial is still continuing. Early findings are encouraging: In an initial group of treated patients, base editing appeared safe, boosted fetal hemoglobin levels, and improved anemia. Heeney presented these results December 7 at the American Society of Hematology Annual Meeting in San Diego.

“The treatment has been truly transformative for Branden,” Heeney says. “Not only are his blood counts and markers of disease activity essentially normalized, but he can now complete daily activities that most take for granted and tackle new experiences previously beyond his reach. It is a joy to see him setting goals that seemed unfathomable just a year or two ago.”