Gene therapy offers humans with sickle cell disease the possibility of a better future

For Evie Junior, living with sickle cell anemia was like running a marathon.

“But it’s a marathon where as you go, the trail gets steeper and then you lose your shoes,” the 27-year-old said. “It gets harder as we get older. Things start to fail and all you can think about is how much worse it gets along the way.”

In sickle cell anemia, a genetic mutation causes blood-forming stem cells, which give rise to all blood and immune cells, to produce hard, sickle-shaped red blood cells. These misshapen cells soon die, leaving an insufficient number of red blood cells to carry oxygen throughout the body. Due to their sickle shape, these cells also get stuck in blood vessels, blocking blood flow and causing painful attacks that occur without warning and can leave patients hospitalized for days.

The disease affects 100,000 people in the United States and millions around the world, the majority of whom are of African or Hispanic descent. It can ultimately lead to stroke, organ damage, and premature death.

As a child growing up in the Bronx, New York, Junior had to have his gallbladder and spleen removed due to complications from the disease, but he refused to let his condition limit him. During the day he played football, basketball, and baseball, although on some nights he suffered from painful fits so severe that he could not walk.

“It was really routine if I had a sickle cell crisis,” he said. “Go to the emergency room, stay in the hospital, get out in a few days and then go back to normal life.”

“I want to create a better future”

When he was 24 and living in Portland, Oregon, Junior started working as an emergency medical technician. He adopted the same mindset – trying to treat his grief episodes as best he could, and hoping they would resolve overnight so he could get back to work. In that period, however, crises became more difficult to manage. She developed pericarditis, an inflammation in the layers of tissue around her heart, and it took six weeks to recover.

“The big concern with sickle cell anemia is that you will die young from some kind of complication or damage to your organs,” he said. “Over the past couple of years, I’ve seen it slowly happen to me and I can only suspect it will continue to get worse. I want to create a better future for myself.”

In July 2019, looking for that future, Junior signed up for a clinical trial for an experimental stem cell gene therapy for sickle cell anemia. The study is led by physician-scientists at UCLA’s Stem Cell Research Center, Dr Donald Kohn and Dr Gary Schiller, and funded by the California Institute for Regenerative Medicine.

The therapy, developed by Kohn over the past 10 years, aims to correct the mutation in patients’ hematopoietic stem cells to enable them to produce healthy red blood cells. Kohn has already applied the same concept to successfully treat several immune system deficiencies, including a cure for a form of severe combined immunodeficiency, also known as baby boil disease.

But sickle cell anemia has proved more difficult to treat with gene therapy than these other conditions. Junior volunteered for the trial knowing there was a chance the therapy would not cure him.

“Even if it doesn’t work for me, I hope it can be a cure later down the road for millions of people,” he said.

In July 2020, Junior received an infusion of his own blood-forming stem cells that had been genetically engineered to overcome the mutation that causes his disease.

“The goal of this treatment is to give him a future, let him plan for college, family or whatever he wants without worrying about being hospitalized due to another pain crisis,” said Kohn, a distinguished professor of microbiology, immunology and molecular genetics, pediatrics, and molecular and medical pharmacology at UCLA’s David Geffen School of Medicine.

Reason for optimism

Three months after his treatment, blood tests indicated that 70% of Junior’s blood stem cells had the new, corrected gene. Kohn and Schiller estimate that even a 20% correction would be sufficient to prevent future sickle cell complications. Junior said he hasn’t had any pain fits since undergoing the treatment and has more energy and feels out of breath less often.

“I noticed a big difference in my overall cardiovascular endurance – even going light jogging with my dogs, I could feel it,” she said.

Junior and his doctors are cautiously optimistic about the results.

“It’s too early to claim victory, but at this point it looks pretty promising,” said Kohn. “Once we’re six months to a year old, if it looks like it is now, I’ll feel very comfortable that it will probably have a permanent advantage.”

After a lifetime of dealing with the unwelcome surprises of the disease, Junior is even more cautious than his doctors. But as the weeks go by, it’s slowly granting a glimmer of hope that soon it could be someone who had sickle cell anemia. To him, that hope feels like an “explosion of happiness” followed by thoughts of all the things he could do with a healthy future: pursuing his dream of becoming a firefighter, getting married, and starting a family.

“I want to be present in my children’s lives, so I’ve always said that I won’t have children unless I can heal,” she said. “But if it works, it means one day I might start a family.”

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(Note to reporters: Watch a video on Evie’s treatment with an experimental gene therapy for sickle cell anemia here: https: //www.Youtube.with/look? v =XmQJpuLx07Y)