Adeno-associated virus as a delivery vector for gene therapy of human diseases

sickle cell disease autosomal recessive :: Article Creator

Trump Administration's NIH Funding Cuts Threaten Research On Sickle ...

Charity Oyedeji:

The language of the letter, the termination notice was shocking to me because it used words like the research was low return on investment and harmful to Americans. And I was like, who wrote this? Like, who wrote this? Because this is racist. Like, this is a racist letter to say that, like, as if my patients are not Americans, or as if studying people with sickle cell disease or even doing equity research is low return.

But improving the health of minority populations and people with sickle cell disease is the opposite. It's high return. It improves the health of Americans. It can prolong life. And I'm doing the opposite of what this termination notice was even saying.

New Jersey Teen Pain-free Thanks To New Sickle Cell Disease Treatment

For the first time in his life, a young New Jersey man is pain-free thanks to a new gene treatment working to cure patients of sickle cell disease.

Gerald Quartey, 18, is the first patient in the Garden State to be treated with the groundbreaking Lyfgenia treatment outside of a clinical trial and following FDA approval in 2023 for patients 12 and older.

"We are essentially curing patients of their disease"

Dr. Stacey Rifkin-Zenenberg, at Hackensack Meridian Joseph M. Sanzari Children's Hospital, explains doctors collect a patient's blood stem cells, which are then genetically modified in a lab.

The patient undergoes intense chemotherapy before the modified cells are infused back in the body to produce new, healthy red blood cells.

"The gene therapy treatment is a treatment where we are essentially curing patients of their disease," Rifkin-Zenenberg said.

The treatment is covered by insurance.

While it's FDA approved for children 12 and older, younger children are being treated with gene therapy through a clinical trial at the hospital and around the country.

"Most of the time, I would just be inside because I was in pain"

All his life, Gerald Quartey has suffered from the debilitating side effects of the rare and life-threatening inherited blood disorder. He needed frequent medical care and couldn't play sports. Even the cold triggered painful episodes.

"It was really rough. I missed a lot school, a lot of things that just, like, normal kids would be doing," he said. "Most of the time, I would just be inside because I was in pain."

It's also been incredibly painful for his mother, Evelyn Quartey, who lost her oldest son, Emmanuel, to sickle cell when he was 7.

"It's been rough," she said. "And there was no treatment at that time."

Gerald completed his treatment at the hospital, ringing a bell and celebrating with the medical staff.

"Just to endure just a few weeks of pain for a lifetime free of pain is, it's definitely worth it," Gerald said.

"So happy and so thankful that he's sickle cell-free," Evelyn Quartey said.

"It just felt really great to know that that chapter of my life is over," Gerald said.

Now pain-free, Gerald plans to head to Penn State to study nursing and psychiatry, hoping to help others, inspired by those who helped him.

'Will It Really Work?': Young Sickle Cell Patient Among The First To ...

WASHINGTON — For Wedam Minyila, hospital rooms have always meant blinding pain. "Like someone is jamming a knife in me," he said.

But for a brief moment on a recent December morning, Wedam, 19, who has sickle cell disease, allowed himself to believe what his doctors had been telling him for months: This visit could be the first step to a cure. As one of the first patients in the world to undergo commercial treatment for the genetic condition, he could start imagining a future free of excruciating pain.

"I choose to partially believe it," he said the day he was admitted to Children's National Hospital in Washington, D.C., for his stem cell collection — the first major step of the revolutionary sickle cell gene therapy process. "But that also comes with the skepticism of: Will it really work?"

Wedam Minyila spent hours on his phone or sleeping during his stem cell collection, as an apheresis machine drew his blood out of his body, spun out the stem cells and then returned the blood back into his veins.Jason Kane / NBC News

It's the same question sickle cell patients nationwide have been asking since the Food and Drug Administration approved two gene therapies that could cure the symptoms of the disease just over a year ago.

Since then, only a few dozen patients nationwide have been able to access it. Paperwork snarls, a multimillion-dollar price tag and patient concerns over serious side effects mean only a limited number of hospitals have treated patients so far.

More than 100,000 people in the United States — 9 in 10 of them Black — have sickle cell disease. The inherited illness causes red blood cells, usually round, to contort into a crescent, or sickle, shape. The sickle-shaped cells often pile up in blood vessels, resulting in excruciating pain, strokes, damage to organs and shorter lives. The new gene therapies, one from Boston-based Vertex Pharmaceuticals and the other from Somerville, Massachusetts-based Bluebird Bio, offer a potential cure.

That's why Wedam pushed past his skepticism — and worked through months of insurance approvals and medical consultations.

"I know what it can mean for me," he said quietly as a team of medical professionals began swarming his bedside. "But until it happens, I'm not really as excited as everybody else."

His mom, Sylvia, watched from the corner of the room, holding her breath. "This is a brand-new thing," she said. "And I never thought that, you know, we would be one of the pacesetters for this. It feels unreal."

But the first step of what she describes as her "miracle" was happening before her eyes: Nurses gave her son a medication to mobilize stem cells normally trapped inside the bone marrow to flow into the bloodstream. A couple of hours later, Wedam was hooked up to what's known as an apheresis machine, which draws blood out of the body and then spins it at high speeds to separate out the millions of stem cells before it returns the rest of blood back into the veins.

Dr. Andrew Campell stepped to Wedam's bedside as the first of the light orange liquid containing his stem cells began collecting in an IV bag hanging next to him.

"You are one of the few in the country and even in the world, you know, taking this big step — gene therapy," said Campbell, director of the hospital's Comprehensive Sickle Cell Disease Program. "It took a lot of bravery, because I know this is still very new in the process."

Wedam looked unfazed. "I had to," he said. "There's not something I could really pass up. So I didn't really have a choice."

A learning curve for hospitals

In coming months, Wedam's cells will be shipped to a lab in Tennessee, where technicians will use a gene-editing tool called CRISPR to modify a gene in the stem cells so they produce red blood cells that are less likely to sickle and block blood flow, resulting in pain crises.

Wedam will need intensive chemotherapy to wipe out his existing stem cells and make room in his bone marrow for the gene-edited cells, which a team at Children's National Hospital will reintroduce into his bloodstream intravenously.

"To be able to deliver a therapy that is a cure and is going to keep him out of the hospital and is likely going to extend life, this is amazing," said Dr. David Jacobsohn, Children's National's chief of blood and marrow transplantation. "It's very, very powerful what we're able to provide now compared to five or 10 years ago."

Wedam, second from right, does a puzzle with his family. His younger brother Wekem, left, was also diagnosed with sickle cell disease. NBC News

Even so, Jacobsohn acknowledged few patients have begun the gene therapy treatment. At Children's National — which was ahead of the curve after it participated in Bluebird Bio's clinical trials — only 10 people, including Wedam, have initiated or finished the process. That's out of a pool of about 1,500 patients with sickle cell disease that the team treats in the Washington area.

"At first, leadership in the hospital, they were super excited. They said: 'We have dozens and dozens of patients eligible. We need to build more beds!' And my feeling is eventually we will, but it's not going to happen right away," he said. "It's been a learning curve for the hospitals, and it's been a learning curve for the insurance companies."

Jacobsohn said his team is ramping up to start one or two patients on the treatment per month — a pace he called "exciting."

"Remember, this is a very high-risk treatment requiring high-dose chemotherapy with potential for complications," he said. "So it's not something that we would want to ramp up too rapidly."

The monthslong treatment Casgevy from Vertex Pharmaceuticals comes with a list price of $2.3 million. Bluebird Bio's Lyfgenia is listed at $3.1 million. Neither includes the cost of care to stay in the hospital or for chemotherapy.

To manage the hefty price tag, insurers have implemented extensive pre-authorization procedures. Both drug companies told NBC News they have yet to see an "ultimate denial" for their drugs.

The procedure is resource-intensive for the limited number of hospitals authorized to deliver it, requiring multiple days in the hospital for the stem cell collection and, months later, multiweek hospital stays for chemotherapy and the reintroduction of the stem cells, Jacobsohn said. In between, the stem cell processing lab needs several months to genetically alter the cells and perform safety checks before it sends them back to the hospital for infusion.

For patients like Wedam, there are other considerations, too. The intensive chemotherapy lasts four days and makes patients extremely ill and susceptible to infection. Many develop ulcerating sores in their mouths, throats and esophagi that make eating nearly impossible. Longer-term, the chemotherapy raises the risk of cancer and infertility.

For all of those reasons, only a single patient has completed the process at City of Hope Children's Cancer Center in Los Angeles. Dr. Leo Wang, a pediatric hematologist-oncologist at the center, says he expects that number to rise rapidly in coming months after the "early adopters" start showing success.

"We're very hopeful that uptake will increase and become more acceptable to people who are maybe a little bit more risk-averse," Wang said. "And we've already seen that where we'll have patients come and ask us about it and say, 'Well, I'd really like to talk to somebody who's been through this already and get their perspective, and then maybe I'll be interested in doing that.'"

'God, you did this for me'

That's one of Wedam's motivations for becoming an "early adopter." "If all of those people could see me and see that it works, they'll have some hope," he said. "Even if it's a tiny bit."

The disease has robbed him of his ability to do much of anything, including getting out of bed. But the idea of a cure has him dreaming of some day becoming a filmmaker.

Near-term, his ambitions are much smaller — he'd like to attend his college classes in person instead of online.

"Now, I don't really keep up with most of my friends, so I'd be able to make new ones," he said. "I'd be able to learn the material better if I'm in person, asking the teacher actual questions. I just think, being a normal person, doing what a normal person would, I think that is what really excites me."

The disease ravaged the Minyila family for close to two decades. In addition to Wedam, his 14-year-old brother, Wekem, also has sickle cell.

Wedam's younger brother Wekem, left, taught himself how to ride a bike after a stem cell transplant cured his sickle cell disease. NBC News

"It's taken almost everything," Sylvia Minyila said. "It's taken our joy."

Wedam, she said, was once a happy boy who loved school and dancing. But once his pain crises started around middle school, she said, he changed.

"He became withdrawn. Anywhere there was bone, he could have pain there," she said. "Anywhere in the house you were, you could hear him moaning. And this is something that I used to think about regularly: 'Am I going to lose him?' Because he was in so much pain."

Until the gene therapy, the only cure for sickle cell disease was a stem cell transplant from a donor. That worked for Wekem after Sylvia discovered she was a match for her younger son. After some scary complications, the procedure was successful.

But antibodies in Wedam's bloodstream prevented the same cure for him.

"I was ecstatic. I said: 'God, you did this for me. But what about my other son?'" Sylvia said, tears rolling down her face. "I wanted the same for Wedam."

She said that when the doctors at Children's Hospital called her just months later to let her know that Wedam might be a good candidate for the new gene therapy, it felt like a double miracle — an answer to her prayers.

"All I kept asking is: 'Is it curative? Is this something that he'll still have to take medications for? Is he going to have pain crises?' They said, 'No.' And I said: 'We're in. We are in.'"

Wedam has seen his younger brother transform since his treatment — even using his new energy to teach himself to ride a bike. The excruciating pain before Wekem's stem cell transplant had made that impossible.

Wekem said he's looking forward to seeing his older brother be healed.

"I feel like it changed the life that he is going to live," Wekem said. "I didn't really think that there was going to be something else that was available to us so he could get treated and cured."

But Wedam remains skeptical. "Maybe 60%," he said of his odds of being cured.

Still, even with the life-threatening complications that may come, he said, if there's any chance of a less painful future, it's worth trying.

NBC News will continue following Wedam Minyila's journey as he begins the next phases of his sickle cell treatment.

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