A Groundbreaking Cure for Sickle Cell Disease

365 days, 8,760 hours, 525,600 minutes, 31,536,000 seconds in a year. Every single moment of every single day, blood is coursing through your body, keeping you alive. However, the blood flowing through your body could be defective and lead to significant health issues. One such blood defectivity is Sickle Cell Disease (SCD), an inherited condition that is caused by defects in the genome. As a result of changes to the genetic composition of the hemoglobin, blood flow can be disrupted. Approximately 20 million people globally struggle with this condition and deal with its challenges. Nonetheless, the United States Food and Drug Administration (FDA) has authorized a treatment, which employs ground-breaking gene editing, to eliminate the disease. The newly approved drug, known as Casgevy, has emerged from years of dedicated research and clinical trials, offering renewed hope for those affected by this debilitating condition.

Understanding Sickle Cell Disease

Sickle cell disease is a hereditary blood disorder characterized by the presence of abnormal hemoglobin, a protein responsible for carrying oxygen in red blood cells. Individuals with SCD inherit two abnormal hemoglobin genes, one from each parent, resulting in the formation of crescent or sickle-shaped red blood cells. As they are not conventionally shaped, these deformed cells can block blood vessels, leading to severe pain, organ damage, and a range of complications.

This disease is specifically common among African Americans. Around 1 in 13 African Americans are born with sickle cell trait and 1 in 365 are born with sickle cell disease. Newborns with the disease typically do not show symptoms until 5 or 6 months of age. Symptoms vary from person to person: some may have regularly occurring symptoms, while others rarely experience any negative traits. The most common early symptoms associated with SCD include yellowing of the skin and whites of the eyes, fatigue or fussiness from anemia, and painful swelling of the hands and feet.

The Journey to a Cure

The journey from laboratory discovery to FDA approval involved rigorous clinical trials to ensure the safety and efficacy of Casgevy. Initial trials demonstrated promising results, with a significant number of participants experiencing a complete resolution of sickle cell symptoms. Long-term follow-up studies have confirmed the effectiveness of the treatment, with patients exhibiting sustained improvements in their overall health and quality of life.

In the comprehensive clinical trials, which included a total of 46 individuals, 29 participants experienced a successful cure. These clinical trials have demonstrated Casgevy’s potential to precisely modify the genetic code responsible for abnormal hemoglobin production. Before, the only cure known for those with sickle cell disease was a bone marrow transplant. Bone marrow transplants require a donor match, painful surgery, and approximately 6-12 months of recovery. In addition, bone marrow transplants pose high risks as the immune system can completely reject the transplant. The Casgevy cure is revolutionary as it factors out the need for a donor and the possible rejection of the transplant.

Casgevy Mechanism of Action

The newly FDA-approved cure, Casgevy represents a paradigm shift in the treatment of sickle cell disease. Developed by Vertex Pharmaceuticals and CRISPR Therapeutics, this innovative therapy utilizes gene-editing technology to correct the genetic mutations that give rise to abnormal hemoglobin. Unlike traditional treatments, Casgevy offers the possibility of a permanent cure by addressing the root cause of SCD at the genetic level.

Casgevy employs a cutting-edge gene-editing technique known as CRISPR-Cas9, allowing scientists to precisely modify the genetic code that produces abnormal hemoglobin. The cure itself is technically a one-time treatment, however, it requires months of preparation. This process involves extracting a patient's bone marrow cells, editing the defective genes, and then reintroducing the corrected cells back into the patient's body. To reinfuse the corrected cells, the medical staff must be sure there are no defective cells left in the body. 

As a way to accomplish this, the patient must undergo chemotherapy to destroy the remaining bone marrow.  By doing so, Casgevy effectively transforms the patient's hematopoietic stem cells into healthy red blood cells that are rid of the mutations that cause sickle cell disease. The required recovery period for this procedure typically ranges from one to two months, after which the patient is released and discharged from the hospital. As the patient embarks on the path to recovery, Casgevy's innovative procedure not only promises liberation from sickle cell disease but also exemplifies the extraordinary potential of cutting-edge medical advancements.

Patient Testimonials

The impact of Casgevy on individuals living with sickle cell disease cannot be overstated. Patient testimonials provide powerful insights into the transformative nature of this cure. Jimi Olaghere, a patient who was given treatment at the Sarah Cannon Research Institute in Nashville, shared his experience, stating, "I'm literally a different person." In terms of the improvements to his quality of life following the treatment, Olaghere emphasizes that, "before, my life was me most of the time in bed writhing in pain, not present because of all the pain medications." Now, Olaghere is able to live more freely and comfortably. For Jimi Olaghere, as well as other recipients, Casgevy has changed their lives forever. These recipients are now able to go about their day without worrying about potential flare ups in symptoms.

The long-term effects of these trials remain unknown, as they have only been set to run for 2 years. Nevertheless, patients are ready to go through with the procedures and are enjoying a new sense of hope for a better future. Christopher Vega, a 31-year-old, from Allentown, Pennsylvania has said that he doesn’t mind the danger of negative long-term effects if the treatment promises a life free of chronic pain. He underwent the treatment in 2020 after years of hospitalization and chronic fatigue. Vega has said he is living a happy life unaccompanied by worrying and pain. These narratives collectively underscore not just the transformative power of Casgevy but also the profound impact it has had on restoring hope, health, and happiness to those affected by sickle cell disease.

Addressing Ethical Considerations

While the approval of Casgevy marks a momentous achievement in the field of medicine, it also raises ethical considerations. The accessibility and affordability of such cutting-edge therapies must be addressed to ensure that the benefits are not limited to only the most privileged. According to ABC News, the treatment costs over 2.2 million per patient. Not only is this cost highly unaffordable, but it does not include other prices such as hospital stay and chemotherapy. In light of these high costs, pharmaceutical companies, policymakers, and healthcare providers must collaborate to develop strategies that make these groundbreaking treatments accessible to a broader population, particularly those in marginalized communities.

Furthermore, many who pursue this treatment are warned of the price beforehand to ensure that they understand the costs. Dr. Asmaa Ferdjallah, a pediatric hematologist and bone marrow transplant physician at the Mayo Clinic in Rochester, stated ”It’s something families have been aware of in the early research stage, and they’ve been very patiently waiting for years. It’s been eagerly awaited by patients and families, but also by providers and physicians.” The determination to undergo treatment remains evident, even in the face of substantial financial burdens, as individuals prioritize relief from the relentless agony caused by sickle cell disease. Considering that this genetic disorder typically reduces one's lifespan by a minimum of 20 years, many find the prospect of grappling with debt a worthwhile trade-off if it translates to an improved quality of life. The profound impact of the disease on both longevity and daily well-being compels individuals to value the promise of a more comfortable and extended life over potential financial strain.

Conclusion

The FDA's approval of Casgevy for the treatment of sickle cell disease represents a watershed moment in the history of medicine. This groundbreaking cure offers hope to millions of individuals affected by SCD, paving the way for a new era in the treatment of genetic disorders. As the scientific community continues to push the boundaries of medical innovation, it is also crucial to address ethical considerations and ensure equitable access to these innovative therapies. With Casgevy, we stand at the threshold of a future where genetic diseases may no longer be a sentence to a lifetime of suffering, but rather a condition that can be treated and ultimately cured.

As we celebrate the milestone of Casgevy's approval, it is unclear what the future holds for research and development in genetic medicine. However, it is important to continue investing in advanced technologies. This will not only improve current treatments but also open up new therapies for other genetic disorders. The approval of Casgevy demonstrates what medicine can accomplish, motivating us to expand the boundaries of medical science and providing hope for those facing genetic challenges.

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Isabel Unzaga is currently a freshman located in New Jersey with a deep interest in science and technology. In her spare time, she enjoys volunteering at her church and seeing friends and family.

References

• FDA approves cure for sickle cell disease, the first treatment to use CRISPR. (2023b, December 8). NBC News. https://www.nbcnews.com/health/health-news/fda-approves-cure-sickle-cell-disease-first-treatment-use-gene-editing-rcna127979/

• What is Sickle Cell Disease? | CDC. (2022, August 18). Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/sicklecell/facts.html

• What is sickle cell disease? | NHLBI, NIH. (2023, August 30). NHLBI, NIH. https://www.nhlbi.nih.gov/health/sickle-cell-disease#:~:text=The%20condition%20affects%20more%20than,born%20with%20sickle%20cell%20trait.

• Sutton-Ramsey, D., & Salzman, S. (2023, December 8). FDA approves gene therapies for sickle cell disease, a “functional cure” for many. ABC News. https://abcnews.go.com/Health/fda-approves-new-gene-therapies-sickle-cell-disease/story?id=105482870

• Getting a stem cell or bone marrow transplant. (n.d.). American Cancer Society. https://www.cancer.org/cancer/managing-cancer/treatment-types/stem-cell-transplant/process.html#:~:text=It%20can%20take%206%20to,the%20stem%20cells%20were%20infused.

• Kaltwasser, J. (2023, March 21). Sickle cell disease cuts 20 years from life expectancy, study finds. AJMC. https://www.ajmc.com/view/sickle-cell-disease-cuts-20-years-from-life-expectancy-study-finds#:~:text=Sickle%20Cell%20Disease%20Cuts%2020%20Years%20From%20Life%20Expectancy%2C%20Study%20Finds,-Mar%2024%2C%202023&text=People%20with%20the%20inherited%20disease,according%20to%20a%20new%20report.