Blood Journal
Leading the way in experimental and clinical research in hematology

A recommitment to sickle cell disease research

  1. Elizabeth G. Nabel and
  2. Susan B. Shurin
  1. Director and Deputy Director, National Heart, Lung, and Blood Institute

Since 1972, the National Heart, Lung, and Blood Institute (NHLBI) has developed and maintained a major research effort to improve the lives of individuals with sickle cell disease (SCD). Resulting scientific advances have led to a number of effective approaches for management and treatment of SCD and prevention of its complications. As a result, today, individuals with SCD live longer and better than could have been imagined several decades ago. Nonetheless, SCD remains a lifelong serious and debilitating illness in most patients. In line with goals articulated in its new Strategic Plan,1 the NHLBI is reexamining and realigning its support for outstanding research that will continue to yield benefit for individuals with SCD.

We recently restructured some of the NHLBI cardiovascular research centers and pulmonary research networks to ensure the best return on our investments in those areas, and the scheduled renewal of the Comprehensive Sickle Cell Centers (CSCC) program provided a timely opportunity to do so for SCD. We asked the National Heart, Lung, and Blood Advisory Council (NHLBAC) to undertake a thorough review of the Institute's SCD research and training programs and their accomplishments. Considered as part of the review were the many responses received to a public solicitation for input from patients and lay and professional constituencies about the top scientific and clinical priorities in SCD.2 The NHLBAC also carefully examined the NHLBI sickle cell research and training portfolio. Its conclusion was that numerous important research needs and scientific opportunities exist and that individuals with SCD throughout the world would benefit if NHLBI resources were reallocated to address them more fully.

At its February 2008 meeting, the NHLBAC endorsed a comprehensive set of recommendations for the future direction of the NHLBI SCD program.3

Seven basic science areas were identified as having exceptional promise for uncovering innovative targets and strategies for SCD therapies: disease mechanisms; new treatment approaches; genes and genetics; molecular biology and biomarkers; vascular biology; erythropoiesis and red blood cell biology; and animal models. Progress in these areas will require stimulation of investigator-initiated research applications, with careful attention to appropriate peer review, and expanded involvement of scientists from areas other than hematology (eg, inflammation, pain pathophysiology, adhesion).

High-priority areas for translational and clinical research include pain pathophysiology and management; fetal hemoglobin induction; major interventional trials of promising alternatives to hydroxyurea; approaches to interrupt pathophysiology such as antiinflammatory, antioxidant, and antiadhesion therapies; curative therapies; and prediction, prevention, and management of severe manifestations and end-organ damage. Also important will be provision of research resources such as repositories for genotype–phenotype data and biological samples, as well as encouragement of resource-sharing among investigators. Innovative approaches will be needed to assist investigators in bringing clinically relevant basic science discoveries to the point where they are ready for human trials.

The recommendations emphasize that an overarching goal in clinical research should be to provide opportunities for individuals and investigators from across the country to participate in clinical research networks. As well, much emphasis should be placed on making prompt and thorough use of the fruits of the research efforts through development of evidence-based practice guidelines and their widespread dissemination via educational programs for physicians, other health-care providers, and patients. Training and career development of investigators in basic and clinical research and in translation will be essential for successful achievement of the goals outlined by the NHLBAC.

Based on the NHLBAC recommendations, the NHLBI is moving forward with the following innovations to its SCD portfolio.

Support for basic research will be expanded through funding of investigator-initiated grant applications and through NHLBI-initiated requests for application (sRFAs) focused on the pathophysiology of SCD, the biology of pain in SCD, fetal hemoglobin switching, and genetic modifiers of disease expression and progression.

The Institute will reconfigure the CSCC program into a Basic and Translational Research Program by funding meritorious projects submitted in response to the recent RFA.4 The program will emphasize fundamental investigations and their translation into initial studies in humans, as well as community translation to promote evidence-based clinical practice. SCD Scholars programs for the career development of young investigators and Summer-for-Sickle-Cell-Science programs for research training and mentoring of high-school students also will be supported as part of a larger effort by the Institute to prepare the next generation of scientists to advance the field of SCD research.

We are also eager to expand NHLBI support of genomic research in SCD beyond the boundaries of current efforts being conducted within the framework of the CSCCs.5 We anticipate developing a program like the Framingham SHARe (SNP Health Association Resource)6 with contributions of genotypic and phenotypic data from many investigators and their patients and free access to qualified researchers.

The NHLBI has requested comments from its constituency regarding interest in joining the RAID (Rapid Access to Interventional Development) program of the National Cancer Institute, which provides contract services to aid in the translation to the clinic of potential new therapeutic agents originating in academia.7 We believe this may offer an avenue for swift progress in evaluation of promising therapeutic approaches such as innovative drugs to stimulate fetal hemoglobin production.

The NHLBI will develop a new Clinical Trials Research Network (CTRN) designed to open participation in clinical research to as many eligible investigators and individuals with SCD as possible. With time, we anticipate that the current SCD Clinical Research Network, established in 2006,8 will become part of the new CTRN.

Finally, the Institute will undertake a focused effort to develop evidence-based guidelines for the care of individuals with SCD across the life-span that can be used by health-care practitioners throughout the world. We also plan to develop an educational campaign, in partnership with the Sickle Cell Disease Anemia Association of America and other patient advocacy groups and professional organizations, to raise awareness about SCD and bring nationwide attention to its diagnosis and treatment.

This is a bold agenda with enormous potential, and we are approaching it with energy and enthusiasm. Our intent is to take full advantage of outstanding scientific opportunities and to make our resources much more widely available—we aim for fair and open access to resources and protocols for individuals with SCD and investigators, whether they live in Boston or Tulsa, Reno or Atlanta. The NHLBI mission is to serve the research community and to bring the fruits of research to the public. We will continue our deep and firm commitment to patients and their families, and we are counting on the full participation of the hematology community to help us fulfill that commitment.