The Only Cure of Scurvy-Cell Disease Can be Squeezed in: Transplant Blood Stem Cells from a Donor Without Cancer
James LaBelle is a paediatric oncologist at the University of Chicago Medicine in Illinois and said that it was difficult to tease out the risks because the clinical trials have been relatively small. It’s not easy to know how well the gene therapies will work in people with severe chronic diseases, because they lack the organ damage or history of stroke that can occur in people with severe chronic diseases.
The increase in risk of bone destruction is already seen in people with scurvy-cell disease. The chemotherapy regimen can also raise the risk of cancer. DeBaun is hopeful that new transplant protocols that use lower doses of chemotherapy will reduce the chances of these side effects.
A few cancer charities that offer assistance to try and retain fertility for women undergoing treatment were reached out to by Woolford. “I don’t have cancer, but I’m getting chemo and radiation,” she explained. “Maybe you can squeeze me in?” The answer wasn’t yes, it was no.
Jones, who resides in Grand Prairie, Texas, wants to be free of the constant threat of a stroke or severe pain crisis. So, in 2020, she opted for the only potential cure at the time: a transplant of blood stem cells from a donor without the disease. She lived for six months preparing for the procedure, during which she underwent radiation, Chemo, and a lengthy hospital stay to destroy her own blood stem cells. The procedure cured her sickle-cell disease, and she is grateful.
Stem-cell transplants and Gene therapy require some kind of treatment in the past. Chemotherapy is time-consuming and risky. Many women who go through it are infertile. While they can have their eggs frozen before treatment, it costs more in the US than in the rest of the world.
All of the treatments are expensive: a stem-cell transplant costs between about US$100,000 and $400,000 and the list price of Casgevy, which was developed by Vertex Pharmaceuticals in Boston, Massachusetts, and CRISPR Therapeutics in Zug, Switzerland, is $2.2 million. These therapies are expensive and not available for many people with scurvy cell disease around the world. In the United States, an effort is under way to make cell and gene therapies available to people who receive publicly funded health care. The programme is planned to go into effect in 25 years, but it’s not yet known how many states will participate. In the UK, the National Institute for Health Care and Excellence decided thatCasgevy is not cost-effective for treating certain diseases, and they asked the developers for more data. As a result, it is not possible to treat the disease through the public health-care system.
At the same time, gene-targeting therapies have also progressed. One therapy, called Lyfgenia (lovotibeglogene autotemcel), provides a working version of the gene that is affected in people with the disorder. The other therapy, called Casgevy (exagamglogene autotemcel), uses CRISPR–Cas9 genome editing to reactivate a form of haemoglobin that is normally inactivated soon after birth. This fetal haemoglobin helps to compensate for the dysfunctional version.
The Journey of a Soldier with Sickle-Cell Disease: From Jones’s Support Group to St. Jude Children’s Research Hospital
Over time, blocked vessels can lead to strokes and damage to organs such as the heart and kidneys. The average life expectancy of people with the disease is less than that of people without it.
But the success stories that make headlines belie the uncertainties and struggles that still surround the treatments. Just as surviving cancer can leave a mark on a person, so can these potentially curative cell and gene therapies. The lack of awareness and support for those who have been cured of any type of cancer is different from the lack of assistance for people with sickle cell disease that affects communities that already face discrimination. There isn’t a lot of education regarding how these patients should be managed according to an expert at St. Jude Children’s Research Hospital.
Then there is the difficulty of getting people with sickle-cell disease, some of whom are traumatized by hospitals and medical procedures, to come back every year for a follow-up examination, says Walters. Some recipients feel like they are done with the disease. The last thing I want to do is give you blood samples’,” he says. I don’t know how we’re going to get more people to participate.
The members of Jones’s support group share their experiences in order to keep up with the latest information. A group of black Londoners with sickle-cell disease in their families develop powers through a drama series on streaming service netflix, and they marveled over it. They groaned in sympathy when one member recalled their struggles to get physicians to take their condition seriously.
The experiences of people who receive gene therapy for the disease will be influenced by her findings. Indeed, recipients of other forms of gene therapy have wrestled with similar problems. Stem-cell transplant recipients are now assigned a psychiatric counsellor who will meet them prior to and after the procedure to help cushion the shock of a new life. Krishnamurti spends months preparing people not only for the procedure, but also for the turmoil that can come afterwards. Do you describe yourself as a warrior? He tells them that they need to train to be a sickle-cell veteran.
A number of recipients of cell or gene therapy feel that they need to fill the space left by their battle with their condition. “The disease becomes the narrative,” says Krishnamurti. “It’s very difficult to change the narrative of a life.”
The team found that transplant recipients reported improvements in physical, mental and social health. Some people struggled and even were happy with the outcome. Feelings of isolation remained a problem for some recipients as well as chronic pain. A lifetime of illness had made the hospital a source of trauma for some. They faced symptoms of post-traumatic stress disorder now that the ordeal was largely over. For others, the hospital was their second home and they mourned the loss of the community when their health improved.
Then there are the mental-health consequences. Even though she was wrestling with the consequences of the condition, Jones’s treatment stripped her of the support networks she had come to rely on. “I feel like I’m in-between,” she says.
For most of her life, Genesis Jones’s daily routine revolved around her illness, the painful blood disorder known as sickle-cell disease. She would run through a mental list of things she hadn’t done in a while, including if she had her pain medications. What was her level of energy? Would she be able to make it through the day?
Jones found out less than a month after her transplant that she had cancer. Three more rounds of chemotherapy and other treatments drove her cancer into remission, but she still struggles with chronic pain in her back and legs caused by decades of tissue and nerve damage from sickle-cell disease. And she worries that signs of mild cardiac inflammation mean that her new stem cells are making immune cells that are attacking her heart.
The effects on Grehan’s health waned over the years after he received the therapy. As a result, physicians often urge recipients to have their blood-clotting proteins checked routinely. When first approached by Nature in March, Grehan was unaware of that concern.
As the therapies grow in size, there is an opportunity to gather data that will address some of the questions. The FDA has said that data from the recipients should be collected by the manufacturers for 15 years after treatment. He says that researchers outside of those companies are also setting up a registry to track the recipients of the therapies.
One of the patients now on that path is DeShawn Chow, 19, of Irvine, Calif. He started treatment at the City of Hope Children’s Cancer Center in Los Angeles earlier this year. His insurance is paying for the treatment, so he’s not concerned about the effect on his ability to have children.
A lot of people are suffering and dying daily, says Gray, a 39-year-old employee at a Walmart. “And we have something now that can put a stop to it. I want people to be free of this type of fear, worry and the level of pain that’s indescribable.”
Bluebird Bio: Why does it take so long for HIV treatments to roll out? How many lives have been affected by a genetic blood disorder?
More government and private insurers are paying for treatments and related care because the companies are helping patients afford them.
We saw a lot of traction on par with our expectations. So we’re very encouraged with what we’re seeing,” says Andrew Obenshain, Bluebird Bio’s chief executive officer. “The hospitals are set up and ready to treat. The payors are paying for it. And the patients are interested.”
But getting all the costs covered can be tricky. And it remains far from clear how the majority of patients who suffer from these genetic blood disorders will ever get them, given that they live in economically disadvantaged countries in places like Africa and Asia where the new therapies remain unavailable.
“It’s almost like I’m battling myself,” says Adekanbi, 29, who lives in Boston. “Sort of like a dark, I don’t know if you’d call it like evil within, [but] sometimes it feels like [it].”
Source: Sickle cell gene therapies roll out slowly
What can you do if you can’t move? Adekanbi’s thoughts on gene therapies for sickle cell diseases roll out slowly
The genetic blood disease causes red blood cells to be sickle-shaped because of a genetic abnormality. These misshapen cells clog blood vessels, damaging vital organs and causing unpredictable, debilitating attacks of pain.
“It gets to the point sometimes where you’re like, ‘I cannot continue living this way,’ ” she says. You feel like you are losing your mind. Sometimes I can’t move. I just lay in one spot and try to distract myself from the pain.”
“I know I would like to have children in the … future,” she says. It’s concerning to me how the process of your body going through to be able to receive gene therapy will affect fertility.
And Adekanbi’s far from alone in wondering what to do. While there’s a lot of excitement about the treatments among sickle cell patients and those suffering from a related disorder known as beta thalassemia, only about 60 of the thousands of patients eligible for the treatment have started the process.
Adekanbi could try to freeze some of her eggs if she decided to do so. But she and other potential patients are concerned about more than their fertility. The treatments are complicated and tiring in other ways.
Source: Sickle cell gene therapies roll out slowly
Strontogen Therapy of Sickle Cells: How Long Can You Stay in the State That You Don’t Live In, or How Fast Can You Get There?
“You could be in the hospital for months,” says Melissa Creary, who studies sickle cell at the University of Michigan School of Public Health. “Even if you’re not in the hospital, you’ll have to be nearby the hospital, which could or could not be in the state that you live in. And then once therapy is finished, there is a very complex process of follow-up for many, many months, again potentially in a state that you don’t live in.”
And some patients worry about possible long-term risks, according to Dr. Lewis Hsu, chief medical officer of the Sickle Cell Disease Association of America.
Both therapies seem safe so far, according to the Boston-based Vertex Pharmaceuticals and the Massachusetts company that makes them.
It is unsurprising that it takes time to get the treatments widely accepted given how complicated and expensive they are, but both companies believe interest is increasing fast.