Advanced Sickle Cell Disease Therapies—Including a Cure—Are on the Horizon

Published on in Children's Doctor

Alexis Thompson, MD, MPH

Case: Langston is a 12-year-old with sickle cell disease whom you have followed in your practice since infancy. He was doing well in school and played youth league soccer, however, in the last few years, these activities have been interrupted by recurrent hospital admissions for painful vaso-occlusive episodes (VOE) and acute chest syndrome. His parents are concerned that Langston tires more quickly, and his school performance has declined. He has mild scleral icterus, and his baseline hemoglobin is 6-7 g/dL. He consistently takes folic acid and hydroxyurea. His family is interested in learning about new therapies, including cures for sickle cell disease. Langston has no siblings.

Discussion: The last decade has seen transformational advances in the care of children with sickle cell disease (SCD), and CHOP remains at the forefront. SCD is an inherited hemoglobin disorders that affects approximately 100 000 Americans and causes chronic hemolytic anemia, severe often debilitating pain, chronic organ damage, and shortened life expectancy. Universal newborn screening across the United States has enabled reliable SCD detection, and evidence-based interventions, such as penicillin prophylaxis to prevent serious infections and transcranial doppler (TCD) ultrasound to identify children who may be at increased risk for stroke, have improved life expectancies.

Today, with early diagnosis and comprehensive care, more than 95% of children with SCD will survive into adulthood in high resource countries like the U.S. With nearly 1 000 children being treated across three locations, the Comprehensive Sickle Cell Center at Children’s Hospital of Philadelphia (CHOP) offers a multidisciplinary, comprehensive model of care that is accessible, well-coordinated, evidence-based, and protocol driven.

Medication Therapies

Hydroxyurea (HU), a medication that induces non-sickling fetal hemoglobin production, reduces red cell adhesion and inflammation, can be safely introduced in early childhood. HU can reduce the severity and frequency of pain, improve growth and reduce many SCD complications. More recently, additional disease-modifying therapies have been approved that can also ameliorate acute and potentially more long-term clinical manifestations (see Table 1 below). While some were initially approved for adults and adolescents, ongoing clinical research studies at CHOP may support their use in younger children.

In collaboration with primary care physicians, the comprehensive, multidisciplinary SCD team at CHOP is well positioned to meet the needs of families like Langston’s. Laboratory testing can help to determine if HU dosing has been optimized. Based on his age, Langston is not yet eligible to receive crizanlizumab, a medication that inhibits red cell adhesion and reduces SCD pain rates when given intravenously monthly. Because Langston has fatigue and a low hemoglobin, he might benefit from voxelotor with or without HU. Voxelotor inhibits sickling, improves oxygen delivery to tissues, and relieves anemia in SCD patients.

The psychosocial specialists at CHOP can assess and, when appropriate, make recommendations to help Langston achieve his educational goals through school-based services or behavioral health interventions.

Center for Curative Therapies

CHOP is the first clinical center in the United States to offer a family-focused, integrated care model called the Curative Therapies for Sickle Cell and Red Cell Disorders (CuRED) Program to help patients like Langston who are interested in curative options.

The multidisciplinary team—which includes specialists in hematology, stem cell transplantation, fertility preservation, psychology, and social services—meets with families to provide education, discuss options and, if appropriate, initiate curative therapies. The CuRED team provides support for the entire patient journey through preparatory processes, the transplant procedure, and long-term follow-up care.

Allogeneic stem cell transplantation can be curative for children with SCD who have an HLA-matched sibling donor. Unfortunately, most patients will not have a suitably matched related donor. Other more experimental options at CHOP include allogeneic transplantation using unrelated or partially matched (haploidentical) related donors.

Gene Therapy’s Promising Future

Gene therapy uses the patient’s own stem cells in combination with one of several approaches to modify the patient’s stem cells ex vivo to ameliorate clinical disease phenotypes. Gene addition of globin gene sequences has led to sustained engraftment with near-complete resolution of pain episodes and stable, normalized hemoglobin levels. The BCL11A gene, which encodes a key regulator of fetal globin production, has been a target for gene therapy in SCD with very promising early results. Other genetic loci are being modified in innovative new studies that may provide additional avenues for research and potential definitive treatment.

At CHOP, strategies for gene addition, gene editing, and base editing in SCD are currently under investigation. While gene therapy is not yet commercially available for SCD, CHOP hematologists and transplant physicians were leaders on gene therapy approach for a related condition, beta thalassemia, which recently received FDA approval and is available at CHOP.

Optimized SCD care is a partnership between primary care and comprehensive SCD center providers. Thanks to clinicians and researchers at institutions like CHOP, with new medical treatments and research advances focused on cure, the future has never been brighter for individuals with SCD.

References and Further Readings

Brandow AM, Liem RI. Advances in the diagnosis and treatment of sickle cell disease. J Hematol Oncol. 2022;15(1):20.

Ware RE, Aygun B. Advances in the use of hydroxyurea. Hematology Am Soc Hematol Educ Program. 2009:62-9.

Krishnamurti L. Hematopoietic cell transplantation for sickle cell disease: updates and future directions. Hematology Am Soc Hematol Educ Program. 2021;2021(1):181-189.

Demirci S, Uchida N, Tisdale JF. Gene therapy for sickle cell disease: an update. Cytotherapy. 2018;20(7):899-910.

Children’s Hospital of Philadelphia. Sickle Cell and Red Cell Disorders Curative Therapy Center (CuRED). Accessed November 21, 2022.

Table 1: Sickle Cell Disease-modifying Therapies


  • ≥ 9 months
    • Hb SS Hb S beta 0 Thal
    • Oral (liquid or capsules) daily
    • Thinning hair or mild hair loss, fingernail discoloration, nausea, diarrhea


  • ≥ 5 years
    • Hb SS Hb S beta 0 Thal
    • Oral (liquid or tablets) daily
    • Constipation, nausea, headache, stomach pain, cough, leg or arm pain, back pain, chest pain


  • ≥ 4 years
    • Any genotype
    • Oral (dissolvable tablets or capsules), daily
    • Headache, diarrhea, stomachache, nausea, tiredness, rash, fever


  • ≥ 16 years
    • Any genotype
    • IV monthly
    • Allergic reactions, nausea, fever, back pain, joint pain

*Can be used in combination therapy with HU; age ranges may change based on studies in progress


Next Steps
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