ANALYSIS: Some sickle cell disease patients now live normal lives. So, why aren't medical journals calling it a cure?
- Charles Reams
- Jul 20
- 7 min read
Updated: Aug 13
If you know a friend who has sickle cell disease or if you have the disease, you know the agony and the life limits this affliction imposes on victims.
What is sickle cell disease SCD?
Sickle cell disease is the most common inherited blood disorder in the United States. Approximately 100,000 Americans and over 4,000 South Carolinians have sickle cell disease. It is a life-limiting disease that affects all parts of the body, causing multi-system complications that often result in life-threatening infections, stroke, and organ damage. People living with sickle cell disease experience periodic episodes of acute pain that typically become more frequent and severe over time. This chronic, painful, life-limiting disease also takes a substantial toll on the mental health of patients and their families. — Statement on the website of Rena N. Grant Sickle Cell Center, MUSC.
Who wants semantics to blur the line between no more symptoms and persistent, knotty details that hold medical editors from acknowledging clear breakthroughs?
There isn't a single medical journal that has conclusively identified a cure for sickle cell disease, but several key publications have reported significant advances in potential curative therapies, particularly gene therapy and gene editing technologies like CRISPR.
CRISPR-Cas9 is a gene-editing technology that allows scientists to precisely target and modify DNA sequences within living organisms. It's a powerful tool derived from a bacterial defense system against viruses, enabling researchers to edit genes with greater accuracy, efficiency, and versatility compared to previous methods.
Differences in understanding sickle cell “cure”: doctors vs. medical journals
While the overarching goal remains the same – to find a lasting solution for sickle cell disease (SCD) – the perspectives and standards regarding a cure can vary slightly between practicing doctors and the scientific community reflected in medical journals.
Doctor's perspective
Practical application and patient focus: Doctors, especially those on the front lines, prioritize managing symptoms and complications, improving quality of life, and making the most effective use of currently available treatments like hydroxyurea, blood transfusions, and newer drugs like L-glutamine, voxelotor, and crizanlizumab.
Bone marrow transplant (BMT) as a "cure": Many doctors consider BMT (also known as stem cell transplantation) as the only established curative option for select patients, particularly those with severe SCD and a suitable matched donor.
Recent gene therapies as "potential cures": They recognize the recent FDA approval of gene therapies like Casgevy and Lyfgenia as exciting breakthroughs offering potential for cure, especially for patients who lack a compatible BMT donor.
Barriers and limitations: Doctors are acutely aware of the barriers to these advanced therapies, including the high cost and complexity of gene therapy, potential long-term side effects, and the need for further research, according to Dr. Butt.
Medical journal perspective
Evidence-based and research-driven: Medical journals, such as The New England Journal of Medicine, focus on presenting robust research findings and advocating for evidence-based guidelines.
Shifting definition of "cure": They highlight the evolution of curative options, including the established role of allogeneic stem cell transplantation (specifically emphasizing the potential of reduced-intensity haploidentical BMT as a viable alternative for adults with severe SCD) and the emerging promise of gene therapies.
Emphasis on gene therapy's potential: Recent articles emphasize the potential of gene editing and gene addition therapies to cure SCD by correcting the underlying genetic defect, particularly for those previously without curative options, according to the American Physiological Society.
Acknowledging limitations and future directions: Journal articles critically assess the current limitations of gene therapies, such as the need for long-term efficacy data, safety concerns, and accessibility challenges, while also pointing to ongoing research and future possibilities.
Bridging the gap
Both doctors and medical journals agree that the field is rapidly progressing, with exciting advancements expanding the possibilities of a true cure for SCD. Open communication between clinicians, researchers, and patients will be crucial to ensure these new therapies are implemented safely, effectively, and equitably to reach all individuals who can benefit.
During his career, Dr. Tisdale has helped over 50 patients with Sickle Cell Disease by using stem cell transplant. While born with the SCD genetic mutation, these people no longer have SCD and live normal lives. — Dr. John Tisdale.
It is worth your time to read on and investigate the evidence for yourself.
Griffin Rodgers and Tisdale, together, subsequently developed a method of curing sickle cell disease through a blood stem cell transplant, which is effective in 90% of patients but not broadly applicable, because only 10% of people with sickle cell disease have a donor match. — National Institute of Health.
Many people with sickle cell disease are living pain-free lives, thanks to the therapies discovered so far.
In late 2023, the FDA approved two gene therapies, Casgevy and Lyfgenia, that offer a potentially curative option for eligible individuals with sickle cell disease (SCD). However, medical journals are hesitant to widely proclaim a cure due to several limitations and concerns surrounding these novel treatments:
Long-term efficacy and safety: While the initial clinical trial results are promising in reducing or eliminating vaso-occlusive crises, the long-term effects and durability of these gene therapies are still under evaluation. There are concerns about potential long-term risks, such as secondary malignancies, which warrant further research and monitoring, according to the National Institutes of Health (NIH).
Accessibility and cost: These gene therapies are very expensive (potentially costing millions of dollars) and are currently only available at a limited number of specialized treatment centers. This creates significant barriers to access for many individuals, particularly those in underserved communities or in regions where SCD is highly prevalent like Africa, according to the National Institutes of Health (NIH).
Eligibility criteria and side effects: Not all individuals with SCD are eligible for gene therapy, with factors like the presence of severe organ damage limiting candidacy. The conditioning regimen, involving chemotherapy to prepare the bone marrow, can also lead to significant side effects, including infertility, according to the Sickle Cell Disease Association of America Inc.
Sebastien Beauzile, a 21-year-old, becomes the first patient from New York to be cured of sickle cell anemia (SCD) using a groundbreaking gene therapy. He received lovotibeglogene autotemcel (Lyfgenia; Bluebird Bio Inc) on December 17, 2024, and has been free of symptoms ever since. His medical team believes this marks a true cure, offering new hope to thousands living with the debilitating genetic disorder. — www.Forbes.com
“This is a fix,” said Jeffrey Lipton, MD, the center’s director of pediatric hematology oncology and stem cell transplantation, told the New York Post. “Other drugs modify the disease, but this is a cure... I suspect this will replace bone marrow transplants in time.”
Lovotibeglogene autotemcel is a cell-based gene therapy that was approved by the FDA on December 8, 2023, for treatment of patients 12 years of age and older with SCD and a history of vaso-occlusive events. It was approved alongside exagamglogene autotemcel (Casgevy; Vertex Pharmaceuticals Inc), which adds modified genes to the body using CRISPR/Cas9, a genome editing technology. Both represent the first cell-based gene therapies for treatment of SCD.6
Lovotibeglogene autotemcel involves collecting a patient's blood stem cells and genetically modifying them to produce HbAT87Q, a gene-therapy-derived hemoglobin that functions similarly to hemoglobin A, the adult hemoglobin produced in individuals unaffected by SCD. HbAT87Q-containing red blood cells are less likely to sickle and obstruct blood flow. After the patient’s blood stem cells are collected, they are treated with high-dose chemotherapy, called myeloablative conditioning, to remove cells from the bone marrow so they can be replaced with the modified cells. The modified stem cells are then reintroduced through a one-time, single-dose infusion as part of a hematopoietic (blood) stem cell transplant. According to data from the clinical trial, the therapy was very successful, resulting in a complete resolution of symptoms within 6 to 18 months in 88% of the trial participants.
Despite the promise of this treatment, the cost of lovotibeglogene autotemcel raises questions about its accessibility. Lovotibeglogene autotemcel is priced at approximately $3.1 million per treatment, which many patients may not be able to afford. This represents the persistent gap experienced by patients with severe, incurable disease; although novel treatments are emerging, cost remains a significant barrier.
To circumvent the need for a donor, Tisdale’s team is exploring gene therapies for autologous stem-cell transplantations. Gene therapy involves withdrawing the patient’s own bone-marrow stem cells and using a viral vector to add a normal copy of the beta-globulin gene to the sickle stem cells. The modified stem cells are then reinfused into the patient, who then produces normal, disc-shaped red blood cells.
Over the past 22 years of research at the NIH, the Tisdale lab has been optimizing engineered viral vectors as a way to deliver the correctly encoded beta-globin gene. One of his latest iterations of viral vectors, when tested in animal models, was up to 10 times as effective as conventional vectors. With clinical trials underway, Tisdale’s team is working toward substantiating gene therapies as a viable method for stem-cell transplantations, even in the case of severe SCD.
Former mentee Courtney Fitzhugh (now a Lasker Clinical Research Scholar in NHLBI) is independently implementing clinical trials involving half-match bone-marrow donors—such as a parent, child, or half-matched siblings—as a viable method of allogeneic (cells that are unlike although from a incompatible though from the same species {relatives}) stem-cell transplantation to treat SCD. “For the first time, we have this dilemma of three potentially curative therapies to choose from: 1) full match, 2) half match, [and] 3) autologous (derived from organisms of the same individual) gene therapies,” said Tisdale.
Summary
Sickle cell disease patients don’t have the luxury of waiting nonchalantly for a grand media event before they make an appointment with the National Institute of Health.
The periodic agony limits their life in myriad ways, challenging families to the brink. For all members of the family, physical and mental health is sorely tried.
At what point will medical editors and doctors get on the same page and prevent semantics from delaying critically needed medical treatment that is available now, with the promise of better treatment tomorrow?
