Aldoris Mbonya-Bate has lived with sickle cell disease (SCD) since childhood. Over the years, she has moved from treatment with one of the first FDA-approved therapies for SCD to participating in clinical research as an adult. Her care at the Johns Hopkins Sickle Cell Center for Adults reflects a broader shift in the field. Treatment has moved from managing complications to therapies that address the disease’s underlying biology. Her experience also illustrates the importance of patients who are willing to participate in research.
Key Takeaways
- Hydroxyurea (Hydrea®; Bristol-Myers Squibb), the first FDA-approved drug for SCD, increases fetal hemoglobin levels. A landmark randomized trial published in 1995 showed that treatment reduced painful crises in adults with sickle cell anemia [1].
- Blood transfusion remains a treatment for some patients with SCD but carries recognized risks, including iron overload, red-cell alloimmunization, and delayed hemolytic reactions [2,3].
- In December 2023, the FDA approved two cell-based gene therapies for patients aged 12 years and older with recurrent vaso-occlusive events. One uses CRISPR/Cas9 gene editing, while the other introduces a functional hemoglobin gene [4,5].
A Disease Defined by Unpredictability
Sickle cell disease (SCD) is an inherited monogenic disorder of hemoglobin, the protein in red blood cells that carries oxygen. A genetic mutation causes hemoglobin to polymerize under low-oxygen conditions, changing red blood cells into rigid, crescent-shaped cells that can obstruct – and damage – small blood vessels. The disease can cause recurrent pain crises, chronic anemia, and progressive damage to organs including the kidneys, lungs, and brain. Symptoms may occur unpredictably.
For Mbonya-Bate, who has built a career in film and television and has traveled internationally despite her diagnosis, that unpredictability has been part of daily life. It has affected decisions about work, travel, and other activities without preventing her from pursuing them. At Johns Hopkins, adult care for SCD includes planning for those uncertainties. The Johns Hopkins Sickle Cell Center for Adults, established in 2008, brings together physicians, nurses, advanced practice providers, and researchers involved in comprehensive care and clinical research in hemoglobin disorders.
Shannon Carroll, CRNP, nurse practitioner manager and lead advanced practice provider at the center, described an approach that considers patients’ goals, including travel. That can include identifying the nearest hospital at a destination and making plans in advance to reduce the potential for problems during a trip.
From Symptom Management to Modifying the Disease
For much of the modern treatment era, SCD management has relied on medications and therapies designed to reduce red blood cell sickling and transfusions that replace affected red blood cells.
Hydroxyurea, an oral medication that increases the proportion of fetal hemoglobin, became the first FDA-approved treatment for SCD in 1998. Fetal hemoglobin does not polymerize in the same way as adult sickle hemoglobin. Evidence supporting hydroxyurea came from the Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH), a randomized, double-blind, placebo-controlled trial published in the New England Journal of Medicine (NEJM) in 1995. Adults who received hydroxyurea had significantly fewer painful crises, episodes of acute chest syndrome, and red-cell transfusions than patients who received placebo [1].
George Dover, MD, professor emeritus of pediatrics and the former director of the Johns Hopkins Children’s Center, is among the investigators whose research into fetal hemoglobin induction, conducted over more than two decades with NIH funding, contributed to the biological understanding behind hydroxyurea’s development and approval.
Blood transfusion, whether used episodically for complications such as stroke or acute chest syndrome or chronically to prevent them, remains an effective treatment for many patients with SCD. Repeated transfusions, however, can cause complications. Exposure to donor red cells can result in alloimmunization, in which the immune system produces antibodies against donor-cell antigens. This can make it harder to find compatible blood for future transfusions and can increase the risk of delayed hemolytic reactions (DHTR), a rare but life-threatening serious immune reaction in which the body destroys both donor and the patient’s own red blood cells. Symptoms of DHTR may resemble a normal sickle cell pain crisis, which can delay proper medical care. [2][3][4]
Chronic transfusion also causes iron accumulation because the body has no physiological mechanism to eliminate excess iron. Over time, iron can accumulate in the liver, heart, and other organs. Patients with iron overload require monitoring and, when appropriate, chelation therapy [3].
These complications have been among the reasons researchers have continued to pursue treatments that can reduce or eliminate long-term dependence on transfusions.
A New Generation of Disease-Modifying and Curative Options
The SCD treatment landscape expanded substantially in December 2023, when the FDA approved two cell-based gene therapies for patients aged 12 years and older with recurrent vaso-occlusive events: exagamglogene autotemcel (Casgevy®; Vertex Pharmaceuticals) and lovotibeglogene autotemcel (Lyfgenia®; Genetix Biotherapeutics)*. [5][6] Both are autologous therapies, meaning clinicians collect a patient’s own blood stem cells and genetically modify them outside the body before returning them to the patient as part of a stem cell transplant procedure.
- Exagamglogene autotemcel is a one-time therapy that uses CRISPR/Cas9 gene editing to alter a genetic switch (a gene called BCL11A) that suppresses fetal hemoglobin (HbF) production after infancy. Editing the regulatory region controlling BCL11A disrupts an erythroid-specific enhancer, allowing fetal hemoglobin expression to resume and giving red blood cells an alternative hemoglobin form that can compensate for the defective adult protein. After myeloablative conditioning with busulfan, the edited stem cells are returned to the patient, where they engraft and repopulate the bone marrow, producing higher levels of fetal hemoglobin that reduce sickling. [5]
- Lovotibeglogene autotemcel uses a different approach. It introduces a functional, modified beta-globin (HBB) gene that allows red blood cells to produce an anti-sickling form of adult hemoglobin. Following gene editing, the genetically modified blood stem cells are ‘instructed’ to produce HbAT87Q, a modified beta-globin that functions similarly to hemoglobin A, the adult form of hemoglobin produced in individuals not affected by SCD. [6].
An editorial published in Molecular Therapy, following the approvals, described these therapies as a new frontier in SCD treatment. Before these approaches became available, allogeneic bone marrow transplantation, which depends on finding a suitable donor, was the treatment that offered the possibility of durable remission [5].
These therapies are not appropriate for every patient. Costs may also play a role in prescribing them.** Eligibility and access requirements apply, and long-term outcomes continue to be evaluated as treatment moves beyond clinical trials. Their approval nevertheless represents an important change in the approach to SCD treatment. Instead of repeatedly treating the consequences of sickling with medications or transfusions, these therapies are designed to alter hemoglobin production in the patient’s own cells and potentially reduce or eliminate the need for chronic transfusion support.
Why Patient Participation Matters
The advances in SCD treatment over the past several decades depended on patients participating in the research that produced them. Mbonya-Bate’s experience illustrates how that participation can develop over time. She initially participated in lower-burden research activities, including questionnaires and observational studies, before enrolling in more involved clinical studies. Her interest in research also grew as she learned more about studies examining the effects of SCD on mental health, including the psychological burden associated with chronic pain. For her, understanding how research could help identify patients who might benefit from therapy or behavioral support for pain management made the value of participating more tangible.
Lydia Pecker, MD, director of research and advocacy at the Johns Hopkins Sickle Cell Center for Adults, linked patients’ willingness to participate in research to the long-term relationships they develop with their care teams. Those relationships matter when patients are asked to participate in research whose benefits may not be immediate or certain. They also affect clinical care. SCD disproportionately affects Black Americans, a population that has historically been underrepresented in clinical trials across many areas of medicine. Long-term relationships between patients and clinicians can support research participation and more representative enrollment.
Progress also depends on cooperation among institutions. Johns Hopkins Medicine participates in the National Alliance of Sickle Cell Centers, a national network of recognized comprehensive SCD centers working to standardize care and expand access to sickle cell specialists. Pecker noted that clinical trials are not necessarily available at every center. Patients may also receive care in different geographic locations during their lives. Collaboration among centers therefore allows research and clinical experience to extend beyond a single institution.
What’s Next?
Mbonya-Bate continues to participate in clinical studies examining new approaches to SCD treatment. She describes her involvement in research as part of her broader advocacy for people living with the disease. She hopes advances in treatment will be available to patients regardless of their circumstances. That includes access to newly approved therapies, which require substantial financial and clinical resources, as well as continued progress in the science.
For Mbonya-Bate, living with SCD still requires planning. But she continues to work and travel, working with her care team to prepare for the unpredictability of the disease rather than allowing it to determine what she can do.
Related Onco’Zine Coverage
- Garcia D. Stem Cell Transplant for Sickle Cell Disease in Childhood Improves Health-Related Quality of Life a Decade Later. Online. Last accessed on September 9, 2026.
Note
* Genetix Biotherapeutics was formerly known as Bluebird Bio before the company’s rebranding.
** Because of the multi-million-dollar price tag, health insurance companies and government payers (such as Medicaid, which covers more than 50% of the U.S. sickle cell population) do not readily approve these therapies. Furthermore, insurers apply strict and rigorous prior authorization criteria to limit their financial exposure. As a result, prescribing physicians cannot simply recommend these therapies based on general eligibility; they must meticulously document that a patient meets all coverage prerequisites. Additionally, ancillary medical requirements may significantly increase the overall treatment cost. To reduce the risk of paying for a treatment that may not deliver the intended results, both healthcare insurers and government payers may require drug manufacturers to enter into outcomes-based or risk-sharing agreements. For example, manufacturers have partnered with the U.S. Centers for Medicare & Medicaid Services (CMS) to develop access models in which an insurer may receive rebates or only pay in full if a patient achieves specific long-term, agreed-upon benchmarks, such as complete transfusion independence or zero severe pain crises.
Highlights of prescribing information
Hydroxyurea (Hydrea®; Bristol-Myers Squibb) [Prescribing Information]
Exagamglogene autotemcel (Casgevy®; Vertex)[Prescribing Information]
Lovotibeglogene autotemcel (Lyfgenia™; Genetix Biotherapeutics)[Prescribing Information]
References
[1] Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med. 1995 May 18;332(20):1317-22. doi: 10.1056/NEJM199505183322001. PMID: 7715639.
[2] Adams RC, Hendrickson JE. Red cell transfusion and alloimmunization in sickle cell disease. Haematologica. 2021 Jul 1;106(7):1805-1815. doi: 10.3324/haematol.2020.270546. PMID: 33792218.
[3] Coates TD, Wood JC. How we manage iron overload in sickle cell patients. Br J Haematol. 2017 Mar;177(5):703-716. doi: 10.1111/bjh.14575. PMID: 28272660; PMCID: PMC5397377.
[4] Hair PS, Heck TP, Carr DT, Watson KD, Price J, Krishna NK, Cunnion KM, Owen WC. Delayed Hemolytic Transfusion Reaction in a Patient With Sickle Cell Disease and the Role of the Classical Complement Pathway: A Case Report. J Hematol. 2021 Feb;10(1):18-21. doi: 10.14740/jh553. Epub 2021 Feb 6. PMID: 33643505; PMCID: PMC7891913.
[5] Leonard A, Tisdale JF. A new frontier: FDA approvals for gene therapy in sickle cell disease. Mol Ther. 2024 Feb 7;32(2):264-267. doi: 10.1016/j.ymthe.2024.01.015. PMID: 38246166; PMCID: PMC10862012.
[6] U.S. Food and Drug Administration. FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. Press release, December 8, 2023.
[7] Fasano RM, Meyer EK, Branscomb J, White MS, Gibson RW, Eckman JR. Impact of Red Blood Cell Antigen Matching on Alloimmunization and Transfusion Complications in Patients with Sickle Cell Disease: A Systematic Review. Transfus Med Rev. 2019 Jan;33(1):12-23. PMID: 30122266.
[8] Johns Hopkins Medicine, Division of Adult Hematology / Johns Hopkins Sickle Cell Center for Adults. Institutional program information. hopkinsmedicine.org/hematology.
National Alliance of Sickle Cell Centers (NASCC). Organizational mission and network information.
This article is based on a patient account originally shared through Johns Hopkins Medicine and is intended for informational purposes for healthcare professionals. It does not constitute medical advice. Individual patient experiences and outcomes with sickle cell disease and its treatments vary, and treatment decisions should be made in consultation with a qualified hematologist.
Featured image: Aldoris Mbonya-Bate ziplines in Puerto Rico for the first time. Courtesy © 2026 Aldoris Mbonya-Bate/Johns Hopkins. Used with permission
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