She cured her disease but she still is in pain
Transplanting Stem Cells and Gene Therapies for Sickle-cell Disease Revisited: The Impact of Lower Treatment Time and Chemotherapy on Long-Term Follow-up
It is important to follow recipients of gene therapies for years after they receive the treatment in order to see whether there is an increase in cancer rates. Lyfgenia carries a warning about cancer risk because two clinical-trial participants later developed leukaemia. MarkWalters, a paediatric haematologist and oncologist, said that long-term data will be crucial to determine whether or not the risk of cancer is associated with a specific form of haemoglobin, which may also lead to blood cancers.
In addition to infertility, the chemotherapy can increase the risk of bone degeneration, which is already elevated in people with sickle-cell disease. The cancer risk can be raised by the Chemo regimen. DeBaun is hopeful that new transplant protocols that use lower doses of chemotherapy will reduce the chances of these side effects.
Woolford reached out to some cancer charities in order to try and retain fertility for women who are going through cancer treatment. “I don’t have cancer, but I’m getting chemo and radiation,” she explained. “Maybe you can squeeze me in?” The answer was no.
Some barriers are falling, however. Michael DeBaun, a specialist in treating Sickle-cell disease at a Nashville, Tennessee medical center, claims that improved transplant protocols have boosted success rates and lowered toxicity. In November, DeBaun and his colleagues showed that stem cells from only partially matched donors — such as a parent — could be transplanted successfully in people with sickle-cell disease who received a lower-than-usual dose of radiation and chemotherapy before the procedure2.
Both stem-cell transplants and gene therapy require chemotherapy before the treatment. Chemotherapy is time-consuming and risky. Women who go through it are often left infertile. They can opt to have their eggs frozen before treatment, but in the United States, the harvesting, freezing and storage of eggs typically costs more than $10,000.
Over the past decade, stem-cell transplants and gene therapies for treating sickle-cell disease have blossomed, offering fresh hope to people with severe illness. Researchers have improved protocols for stem-cell transplants, and the US Food and Drug Administration (FDA) approved two genetic treatments last year — including the first CRISPR-based genome-editing therapy the agency has ever authorized.
At the same time, gene-targeting therapies have also progressed. There’s a therapy that can help those with the disorder by giving them a working version of the gene. The other therapy uses genome editing to reprogram haemoglobin that is normally inactivated soon after birth. This fetal haemoglobin helps to compensate for the dysfunctional version.
Sickle Cell Disease, the Narrative, and the Next-Geness World: The Case of Jones and Krishnamurti
Over time, damaged vessels can cause strokes and damage organs such as the heart and kidneys. In the United States, people with sickle-cell disease have an average life expectancy that is some 20 years shorter than people without it1.
Sickle-cell disease is caused by a mutation in the gene encoding a component of haemoglobin, the oxygen-carrying protein complex found in red blood cells. The cells can be shaped like a crescent, or they can be shaped like a round shape. Those cells can cause severe pain, called a pain crises, if they block blood vessels that have oxygen-rich tissues in them.
So Adekanbi was thrilled when, in late 2023, the Food and Drug Administration approved the first genetic treatments for sickle cell, a disease that disproportionately affects Black people like her and has long been neglected by medical science.
The members of Jones’s support group shared stories and experiences while sifting through misinformation along the way. In a recent virtual gathering, the group marvelled over Supacell, a drama series on streaming service Netflix in which a group of Black Londoners with sickle-cell disease in their families develop superpowers. They groaned in sympathy when one member recalled their struggles to get physicians to take their condition seriously.
Similar concerns weigh on people who have received gene therapies for other conditions, and that number is growing rapidly. More than 600 genes are being tested around the world, with 30 of them approved in the United States. Clinicians and patients are trying to figure out how to support each other after their treatment. Anirban Basu, a health-care economist at the University of Washington, says that genes will change the landscape. “This is coming.”
Many people that get cell or gene therapy feel like they need to fill out the space left by the condition that they had spent a lifetime fighting. Krishnamurti says that the disease becomes the narrative. It is difficult to change the narrative of a life.
Positive changes for transplant recipients were found by the team. Some people struggled, even though they were happy with the outcome. Chronic pain and bone degeneration remained a problem for some recipients, as did feelings of isolation4. A lifetime of illness had made the hospital a source of trauma for some. Post-traumatic stress disorder can be a symptom of it after the battle is over. For some others, the hospital was a second home and they mourned the loss of the community when their health improved.
She was turned away from doctors when she needed help for her pain because her blood tests did not indicate she had sickle-cell disease. She says that they asked why she was here. “Basically, you have to suffer alone at home.”
For most of her life, Genesis Jones focused on her illness and its associated pain, the painful blood disorder known as sickle-cell disease. She was running through a mental checklist each time she left the house, trying to remember if she had her pain medication. What was her energy level? Would she be able to make it through the day?
Jones discovered that she had cancer less than a month after her transplant. She went through 3 more rounds of treatments for her cancer but still has chronic pain in both her legs and back because of the damage done to her muscles by the 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 Gene-therapy field has a hard time following up long-term. A videographer in Manchester, UK named Jack Grehan was treated for a blood-clotting disorder five years ago. For the first few years after receiving the therapy, he returned to the hospital for follow-up exams each time he was asked to come. But now he lives two hours away from the treatment centre and is juggling childcare and a new job. He has not had a single bleeding episode since receiving the treatment, and he stopped going to check-ups two years ago. Once his life is back to normal, he will happily return and give them more.
As the therapies expand from clinical trials to hospitals, there is an opportunity to collect data that would address these questions, LaBelle says. The FDA has suggested that gene-therapy manufacturers should collect data from the recipients of their products for up to 15 years after treatment. There is a registry that will be set up by researchers outside of those companies.
One of the patients now on that path is DeShawn Chow, 19, of Irvine, Calif. He started treatment at the Children’s Cancer Center of Los Angeles earlier this year. His insurance is paying for the treatment, and he’s not concerned about the effect it might have on his ability to have children.
Gray, who works full time at Walmart, says many people are suffering and dying every day. “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.”
What are the costs of medical treatments for tickle cell gene therapies? A case study in a blood disordered environment: How much do insurers pay? How can patients afford it?
More government and private insurers are paying for treatments as the companies try to help patients afford them.
“We do see a lot of traction pretty much on par with what we thought would be the interest level. 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. Because the new therapies for these genetic blood disorders remain unavailable in places like Africa and Asia, it’s not clear how the majority of patients who suffer from these disorders will ever be able to get them.
“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
How will you feel? And what would you do if you decide to stop living in pain? A story about a friend of a woman with rare genetic blood disease
The rare genetic blood disease is caused by a genetic mutation that causes red blood cells to become deformed, sickle-shaped. These misshapen cells clog blood vessels, damaging vital organs and causing unpredictable, debilitating attacks of pain.
Sometimes it is necessary to stop living the way you are. You feel like you are losing your mind. Because sometimes I just can’t move. I just lay in one spot and try to distract myself from the pain.”
One big hesitation is over the chemotherapy needed to make room for genetically altered cells in her bone marrow. The cells have been altered to relieve the symptoms of the disease. But the chemotherapy would endanger her chances of having kids.
Adekanbi is not the only one 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 said she would attempt to freeze her eggs if she were to do so. Potential patients are more concerned with more than a couple of things. The treatments are very demanding and complex in other ways.
Source: Sickle cell gene therapies roll out slowly
The Road Towards a Safe Therapy for Sickle Cell Diseases: Theoretical Overview and Patient Expectation Aspects
“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.”
Some patients with the disease worry about the long-term risks.
Both therapies have been said to be safe so far by the companies that make them.
It is not surprising that it is taking so long to get the treatments widely accepted because of how expensive they are.
A team of US researchers has claimed they’ve transplanted the first gene therapy in sickle cell disease patients with only partially matched stem cells from a parent. The study, published in the journal Blood, also found that stem cells from only partly matched donors were able to be transplanted successfully in people with sickle-cell disease who received chemotherapy before the procedure.