On World Sickle Cell Day, we celebrate a historic milestone: the first patient officially cured of sickle cell disease through gene therapy. As a clinical nurse specialist who has witnessed the devastating impact of sickle cell disease on patients’ lives, I’m excited to share insights on these groundbreaking treatments that could transform care for those affected by this debilitating genetic disorder.
The Science Behind Gene Therapy for Sickle Cell Disease
Currently, there are three types of gene therapies being used to treat sickle cell disease. The first approach is gene inactivation, which renders the problematic gene ineffective. Gene inactivation removes the function of a gene. The second is gene editing or correction, the science behind Vertex Pharmaceuticals’ Casgevy therapy, which replaces the faulty gene with a healthy one. This is how gene editing, or gene correction, works:
Fetal Hemoglobin is the hemoglobin that can prevent sickling of red blood cells and pain crises. This is the hemoglobin you are born with, but shortly after you are born, it is replaced with adult hemoglobin. BCL11A is a gene that tells the body to make less fetal hemoglobin.
Casgevy uses the CRISPR/Cas9 enzyme to cut a specific spot in the BCL11A gene. When the BCL11A gene is edited, this will help the body make more fetal hemoglobin. When the body has more fetal hemoglobin, this will help the red blood cells from turning into a sickle shape.
The third method, gene addition, adds a functional gene to the patient’s cells and is the technology behind Bluebird Bio’s Lyfgenia—the treatment that successfully cured the first patient in New York, exhibiting no symptoms since his infusion in December 2024.
The ultimate goal of these therapies is to prevent red blood cells from sickling and clumping together, which causes the excruciating pain crises that characterize this disease. When successful, patients may experience reduced pain or potentially live pain-free lives.
The Patient Journey: A Year-Long Process
Patients considering gene therapy should understand it’s a lengthy and complex process that can take a year or more from start to finish. The journey begins with a comprehensive screening to determine eligibility, including infectious disease testing and evaluation of major organ functions (heart, lungs, liver, and kidneys).
For female patients, fertility preservation discussions are essential, as the treatment may affect reproductive capabilities. Insurance pre-certification follows, and interestingly, the insurance company may dictate which gene therapy product the patient receives.
Once approved, the pharmaceutical company reserves a slot for the patient. The treatment process begins with hypertransfusion—an exchange transfusion where sickle cells are removed and replaced with healthy red blood cells. Next comes stem cell mobilization with medications to stimulate stem cell growth, followed by the collection of these cells.
The collected stem cells are sent to the pharmaceutical company to create the gene therapy product, a process that can take approximately 4 to 6 months, depending on the gene therapy product. Upon returning to the hospital, patients receive chemotherapy to prepare their bodies for the gene therapy infusion. If successful, their blood cells will no longer sickle, eliminating the painful episodes that define this disease.
Risks and Considerations for Gene Therapy
Despite its promise, gene therapy carries significant risks. Patients become immunocompromised during treatment, increasing their risk of infection. Blood counts may drop, raising the possibility of bleeding and stroke. Some patients may experience infertility, and these side effects could manifest months or even years after treatment.
In rare cases, patients have developed leukemia following gene therapy. Sadly, rarely, some patients have died. The treatment’s intensity, including chemotherapy, places considerable stress on the body.
Barriers to Access to Gene Therapy
The primary barrier to these potentially curative treatments is cost—ranging from $2-5 million per patient. While insurance may cover the expense, many patients remain ineligible due to pre-existing organ damage, particularly among older individuals with advanced kidney disease.
Ideal Candidates for Gene Therapy
The ideal candidates for gene therapy are typically patients aged 12 years and older. The earlier the intervention, the better, as prolonged sickle cell disease leads to cumulative organ damage that may disqualify patients from treatment. Candidates must also be prepared for multiple hospital stays, especially if they do not produce enough stem cells on the first collection attempt. Enough stem cells will need to be collected for the gene therapy product as well to have back up stem cells if needed during the treatment process.
On this World Sickle Cell Day, these advancements give us reason for hope. While gene therapy isn’t without risks and challenges, it represents our most promising path toward a cure for a disease that has caused immeasurable suffering for too long.
Dr. Brenda Merriweather is a Clinical Nurse Specialist who recently earned her Doctorate of Nursing Practice from Walden University. With a deep passion for improving care for individuals with Sickle Cell Disease, she has held several key roles in prominent healthcare institutions, including Baptist Health System, Vanderbilt University Medical Center, Johns Hopkins University, and the National Institutes of Health.
