Advances in the Treatment of Sickle Cell Disease

Sargam Kapoor, Jane A. Little, Lydia Pecker

Research output: Contribution to journalReview article

Abstract

Sickle cell disease (SCD) is a monogenic disorder that afflicts approximately 100,000 Americans and millions of people worldwide. It is characterized by hemolytic anemia, vaso-occlusive crises, relentless end-organ injury, and premature death. Currently, red blood cell transfusion and hydroxyurea are the major disease-modifying therapies available for SCD. Hematopoetic stem cell transplant is curative, but barriers to treatment are substantial and include a lack of suitable donors, immunologic transplant rejection, long-term adverse effects, prognostic uncertainty, and poor end-organ function, which is especially problematic for older patients. Gene therapy to correct the βs point mutation is under investigation as another curative modality. Deeper insights into the pathophysiology of SCD have led to the development of novel agents that target cellular adhesion, inflammation, oxidant injury, platelets and/or coagulation, vascular tone, and hemoglobin polymerization. These agents are in preclinical and clinical trials. One such agent, L-glutamine, decreases red blood cell oxidant injury and is recently US Food and Drug Administration approved to prevent acute pain episodes of SCD in patients 5 years of age or older. The purpose of this review is to describe the currently established therapies, barriers to curative therapies, and novel therapeutic agents that can target sickle cell hemoglobin polymerization and/or its downstream sequelae. A PubMed search was conducted for articles published up to May 15, 2018, using the search terms sickle cell disease, novel treatments, hematopoietic stem cell transplantation, and gene therapy. Studies cited include case series, retrospective studies, prospective clinical trials, meta-analyses, online abstracts, and original reviews.

Original languageEnglish (US)
Pages (from-to)1810-1824
Number of pages15
JournalMayo Clinic Proceedings
Volume93
Issue number12
DOIs
StatePublished - Dec 1 2018

Fingerprint

Sickle Cell Anemia
Oxidants
Polymerization
Genetic Therapy
Wounds and Injuries
Therapeutics
Clinical Trials
Sickle Hemoglobin
Erythrocyte Transfusion
Premature Mortality
Hydroxyurea
Hematopoietic Stem Cell Transplantation
Hemolytic Anemia
Graft Rejection
Acute Pain
United States Food and Drug Administration
Cell- and Tissue-Based Therapy
Glutamine
Point Mutation
PubMed

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Advances in the Treatment of Sickle Cell Disease. / Kapoor, Sargam; Little, Jane A.; Pecker, Lydia.

In: Mayo Clinic Proceedings, Vol. 93, No. 12, 01.12.2018, p. 1810-1824.

Research output: Contribution to journalReview article

Kapoor, Sargam ; Little, Jane A. ; Pecker, Lydia. / Advances in the Treatment of Sickle Cell Disease. In: Mayo Clinic Proceedings. 2018 ; Vol. 93, No. 12. pp. 1810-1824.
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