Sickle cell: ‘The revolutionary gene-editing treatment that gave me new life’

Jimi Olaghere thought he would have to wait decades to be freed from his sickle cell disease – but now scientists have manipulated his blood to overcome the disease that caused him constant pain.

“It’s like being born again,” says Jimi, one of the first seven sickle cell patients to have benefited from a revolutionary new gene-editing treatment being tested in the United States. He says it changed his life.

“Looking back, it’s like, ‘Wow, I can’t believe I lived with this.'”

Jimi, 36, has lived with sickle cell anemia since childhood. “You must always be in a war mentality and know that your days will be full of challenges.”

The disease tends to run in families. It is caused by a genetic mutation that causes the body to produce abnormal hemoglobin. This is the protein that gets packed into red blood cells and carries oxygen around the body. Red blood cells are normally round and squishy, ​​but mutant hemoglobin can make them rigid and take on their characteristic crescent shape.

These sickle cells struggle to navigate the body’s blood vessels and get stuck, creating blockages that stop blood flow. The risk of heart attack, stroke, and organ damage is higher in people with sickle cell disease. Jimi may need a hip replacement because some of his bone tissue died after he was drained of blood – an irreversible condition called avascular necrosis.

Pain is a lifelong companion for Jimi. It’s like having “shards of glass running through your veins or someone hitting your joints with a hammer,” he says. “You wake up in pain and go to bed in pain.”

But the hallmark of sickle cell disease is the severe episodes of pain called crises, which require hospital care and morphine to relieve the pain. For years, Jimi was in and out of the hospital almost every month. Winters were the worst – as cold weather constricts blood vessels near the skin, increasing the risk of congestion. For this reason, Jimi moved his family across the USA – from New Jersey to the warmer climes of Atlanta, Georgia.

The disease has affected every aspect of his life. He’s a technology entrepreneur because he can’t imagine any employer would approve of his frequent hospital visits. To escape the constant pain, Jimi found “bags of happiness” in video games and watched Liverpool play football.

His family urged Jimi to participate in other clinical trials or to have a bone marrow transplant — which is an option for some people with sickle cell disease. But he thought they would require too much time in the hospital to improve his quality of life. Instead, he pinned his hopes on a yet-to-be-invented cure. He told his family, “One day in the future, probably 20 to 50 years from now, I will have my DNA edited and it will heal my sickle cell.”

The future came much sooner than he had imagined.

In late 2019, Jimi read an article about a new clinical trial involving gene editing and immediately emailed the medical team. A month later, Jimi and his wife Amanda, who was eight months pregnant, traveled to the Sarah Cannon Research Institute in Nashville to see if he would qualify. When news broke that he had been included in the process, Jimi said it was “the best Christmas present ever”. And then he got lucky. The pandemic threatened to disrupt the process as a growing number of domestic flights were canceled due to low passenger numbers, but he was able to commit to a four-hour drive by car for each individual session.

In the study, scientists would genetically engineer his body to stop producing that tainted hemoglobin.

First they had to get to the part of the body that makes red blood cells – stem cells that live in the spongy marrow at the center of our bones. Then, in January 2020, Jimi received medication that flushed stem cells from his bone marrow into the bloodstream. Then he was put into an apheresis machine to extract the stem cells from his blood.

“You sit there for eight hours and this machine literally sucks all your blood out,” he said.

By the end, he was physically, mentally and literally exhausted and would require a transfusion to replace the blood drawn. This was the hardest part of the whole process for Jimi and he went through it four times.

Jimi went home to recover after the last donation, but the harvested stem cells were just beginning their journey.

Scientists were about to pull off an impressive genetic trick that would turn back time in Jimi’s blood.

When we are still in the womb, our body uses a different type of hemoglobin called fetal hemoglobin. This holds oxygen tighter than adult hemoglobin and is essential for a developing baby to draw oxygen from its mother’s bloodstream.

After we are born, a genetic switch is flipped and we begin to produce adult hemoglobin. Crucially, only the adult form of hemoglobin is affected by sickle cell anemia.

This genetic switch, catchily named BCL11A, was identified in the mid-2000s. And advances in gene editing meant scientists now had the tools to flip it.

“Our approach is to turn off that switch and increase fetal hemoglobin production again, which basically turns the clock back,” says Dr. Haydar Frangoul, who treated Jimi at the Sarah Cannon Research Institute.

Jimi’s stem cells were sent to Vertex Pharmaceuticals and Crispr Therapeutics labs where the genetic editing would take place.

In September 2020, it was time to insert the engineered cells into Jimi’s body. “Actually, it was the week of my birthday. So it was almost like I got a new life,” he says.

First, Jimi had chemotherapy to destroy the stem cells in his body that produced sickle blood cells. Then the genetically engineered ones were infused into his body to give him new and hopefully sickle-free blood.

The procedure was exhausting, but about two weeks later, Jimi emerged as a whole new person.

“I remember waking up with no pain and feeling lost,” he says. “Because my life is so connected with pain, it’s just a part of me. It’s strange that I don’t experience it now.”

dr Frangoul says the data from the first seven patients is “downright amazing” and represented a “functional cure” for their disease.

“What we’re seeing is that patients are returning to their normal lives, none have had to be hospitalized or seen a doctor for complications related to sickle cell,” says Dr. Frangoul.

The same genetic procedure was performed on a total of 45 patients with sickle cell anemia, or another blood disorder called beta thalassemia, which is caused by faulty hemoglobin. But full data is still being compiled.

Finally pain free, Jimi feels he can finally be the person he “always felt inside.” He says the illness made him more introverted because it forced him to stay at home and be careful.

“I have this analogy that I use. When my son was first born, I saw him looking out the car window and seeing the world as a new person for the first time. I feel almost the same way. I live life as a new person.”

And he feels he can finally be the parent he wanted to be. “Just being able to walk my son was something I thought I’d miss out on.”

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