ARRA Investments in Sickle Cell Disease
Public Health Burden
Sickle cell disease (SCD), the most common inherited blood disorder in the United States, affects about 80,000 Americans, including 1 in 500 African Americans. SCD is characterized by anemia, severe infections, acute and chronic pain, and organ damage.
Although SCD has no cure, the drug, hydroxyurea (HU), decreases the number of painful crises, transfusions, and life-threatening complications by inducing formation of fetal hemoglobin (HbF), which prevents sickling of cells in SCD patients. While some children can be cured of SCD by hematopoietic stem cell (HSC) transplantation, better therapies are needed for patients of all ages. ARRA funds will support research to:
Test a new approach that matches adult patients with a team of doctors, nurses, and social workers to facilitate HSC transplantation.
Determine if using blood-thinning medications to treat high blood pressure in the vessels of the lungs (pulmonary hypertension [PH]), which affects approximately 30 percent of adult SCD patients and is associated with a high risk of death, slows the progress of PH and lowers the risk of death.
Basic research is needed to develop new drugs, increase understanding of red cell dehydration in SCD, and improve gene therapy. ARRA funds support basic SCD research, including studies to:
Investigate the biological mechanisms involved in regulation of HbF production to enable development of more effective HbF-inducing drugs.
Explore the reasons for red cell dehydration, a hallmark of SCD, to enable targeted pharmaceutical approaches.
Enhance the effectiveness of gene therapy for SCD by identifying and evaluating methods to select and increase the numbers of genetically corrected blood cells following therapy.
Major advances have been made in the treatment of infections and strokes in children with SCD, but further research is needed to develop new treatments for many of the other common problems that affect patients with SCD. Translational SCD research supported by ARRA funds will:
Examine genetic differences that may explain variation in SCD severity. The results may lead to the development of tests to predict which patients are likely to develop problems in the future.
Look for drugs that act on a newly discovered gene that may stimulate the body’s ability to produce more HbF.
Investigate a new treatment that may interfere with a chain reaction that influences episodes of severe pain experienced by patients with SCD.
Red blood cell (RBC) transfusions are administered to patients with SCD to ameliorate low blood counts, to prevent and treat complications, and to prepare them for surgery. Repeated transfusions complicated by the development of antibodies (sensitization) against donor RBCs make additional transfusions more difficult. ARRA funds have been awarded for projects to:
Identify patients at increased risk of developing antibodies. More precise matching techniques can then be used to reduce the risk of sensitization.
Develop an intervention to increase the number of African American blood donors and potentially reduce the risk of sensitization in SCD red cell transfusion recipients.
Use magnetic resonance imaging to identify SCD patients who, because of many blood transfusions, have increased amounts of iron in their liver and pancreas and should be treated with chelation drugs to help dispose of the extra iron and avert heart and liver problems.
Innovative approaches are investigating the effect of newborn screening for SCD on patients, families, and providers; patient experiences in routine and emergency care environments; and use of communication technology to improve access to care and responses to pain. Investigators will:
Develop and evaluate improved processes of communication after newborn screening for SCD
and explore parents’ responses when newborns are identified as carriers of SCD.
Evaluate experiences of respect, trust, communication, adherence to therapy, appropriateness of care, and health outcomes for SCD patients in routine care environments, emergency departments, and inpatient settings.
Test the effectiveness of a wireless pain-intervention program that includes a cell phone/PDA with pain questions; a web link to educational materials, a psychologist, and a nurse practitioner; and a peer social-support network by cell phone/PDA.
-- Matched and Haploidentical Transplantation for Adults with Sickle Cell Anemia -- Flomenberg, Neal (PA)
-- Coagulation Activation in Sickle Cell Patients -- Ataga, Kenneth (NC)
-- Mechanisms Underlying the Pharmacologic Induction of Fetal Hemoglobin -- Lowrey, Christopher H. (NH)
-- Mechanisms of Endothelin 1-Induces Sickle Cell Pathology -- Rivera, Alicia (MA)
-- Testing the Safety and Efficacy of Inhibitory RNA Mediated Purine Analog Resistance -- Porter, Christopher C. (CO)
-- Genetic Diversity of Sickle Cell Anemia -- Steinberg, Martin (MA)
-- Extending GWAS at the BCL11A Locus to Novel Therapeutics for HbF Induction -- Orkin, Stuart -- (MA)
-- Treatment of Sickle Cell Crisis with Inhibitors of NKT Cell Activation -- Nathan, David (MA)
-- Transfusion Associated Immune Hemolysis -- Yazdanbakhsh, Karina (NY)
-- Feasibility of Expert System to Promote African American Blood Donation for SCD -- Robbins, Mark L. (RI)
-- Iron-Mediated Vascular Disease in Sickle Cell Disease -- Wood, John (CA)
-- A Rapid Throughput Feedback Intervention for Population-Scale Communication Quality Assurance Projects -- Farrell, Michael Henry (WI)
-- Improvement of Communication Process and Outcomes After Newborn Genetic Screening -- Farrell, Michael Henry (WI)
-- Respect, Trust, and Patient Outcomes in Sickle Cell Disease -- Beach, Mary Catherine (MD)
-- Wireless Pain Intervention Program for At Risk Youths with Sickle Cell Disease -- Jacob, Eufemia (CA)
Page Last Updated on June 30, 2018
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