New Directions for Sickle Cell Therapy in the Genome Era

New Therapies for Sickle Cell Anemia in the Genome Era

Attendees' Votes Among Options for Research on New Therapies for Sickle Cell Disease

Conference attendees were asked to cast votes among approximately 30 priorities that had emerged during the meeting as options for furthering research aimed at developing new, more effective therapies for SCD. All participants were given 100 votes each, which they could then split among any of the possible priorities. Tabulation of those votes is shown below:

Twenty-two (22) percent of all votes were cast in favor of an innovative multidisciplinary Sickle Cell Disease Research Network with a central prospective registry of several thousand well phenotyped patients.

Features of this might include:

  • DNA/plasma repository, cell lines, mRNA (when both symptomatic and asymptomatic)
  • Standardized phenotypes
  • Inclusion of environmental, social, cultural, genetic data
  • Newborn cohort
  • Quality of life data
  • Careful attention to human subjects issues, well consented with recontact possible
  • Collaborative community partnerships
  • Open access to materials and data
  • Longitudinal follow up
  • Clinical trials database

Ten (10) percent of all votes were cast in favor of bringing new people and disciplines into the field and training the next generation of researchers. This would include integrating genomics, proteomics, and high-throughput screening expertise into sickle cell disease research. It might also include increasing the number of basic, clinical, and social science researchers, as well as nurses and allied health professionals, doing research on sickle cell disease. Possible mechanisms for accomplishing this might include grant supplements and loan repayment programs.

Eight (8) percent of all votes cast were cast in favor of defining the genetic basis of phenotypic variability. Methods to this might include case/control studies and/or studies of monozygotic and dizygotic twins, of sib pairs and of individuals with unusually mild phenotypes. International collaboration would be particularly helpful here.

Five (5) percent of all votes were cast in favor of establishing a working group to define SCD severity by strict standardized criteria. This might include innovative techniques for more precise definition of phenotypes, e.g., for acute chest syndrome and for stroke, as well as the use of laboratory measures.

Four (4) percent of all votes cast were cast for each of the following:

  • Genomics tools service centers, including such resources as haplotype maps, whole genome arrays, etc.
  • Target-based compound screens to explore such possibilities as hemoglobin F induction (for which would need improved cell lines that express beta-globin), nitric oxide, antithrombotics/anticoagulants and other agents that might affect adhesion, inflammation, or oxidation
  • Proteomics and transcriptomics on erythrocytes, reticulocytes, bone marrow, and other tissues
  • Clinical trials that included an extensive research network, DNA collection, greater involvement of patient advocacy groups, and attention to the psychosocial aspects of SCD
  • Core resources of biological materials, including such materials as transgenic mice for drug screening, a DNA construct repository, antibodies to sort erythroid progenitors, and cord blood banks for SCD and thalassemia cells
  • Development of a new model to study hemoglobin F reactivation, especially in adult cells, such as human cell lines that respond to switching agents
  • To the extent possible, NIH attempting to catalyze more effective care and broader access to care of SCD patients, perhaps through a standardized care model.

Three (3) percent of all votes cast were cast for each of the following:

  • Building better relationships with international investigators, including in research regarding ethical, legal, social, and cultural aspects of SCD
  • Community and public education programs
  • Resources for drug development, e.g., toxicology, non-human primates, and infrastructure for Phase I and II trials, including for drugs that already show promise
  • New and better gene transfer vectors that are safe and efficient, including non-integrating systems, targeted integration, and homologous recombination.

Two (2) percent of all votes cast were cast for each of the following:

  • Phenotypic compound screens, applicable to hemoglobin S polymerization and sickling of red blood cells
  • Genetic modifier screens, for humans, mice, and zebrafish
  • Biomarkers for disease severity and monitoring of clinical trials
  • Timely initiation of gene therapy trials
  • Research into such ethical, legal, and social issues as self-identity, ancestry, race, stigma, discrimination, trustworthiness.

One (1) percent of all votes cast were cast for each of the following:

  • Education of the public
  • Better and more accessible animal models - non-human primates, rabbits, rats, mice, zebrafish
  • Human embryonic stem cell methodologies, including derivation of SS embryonic stem cells.

Less than once (<1) percent of all votes cast were cast for each of the following:

  • Stem cell purification strategies
  • Investigation of barriers to research participation
  • New technologies for understanding the molecular switching mechanism, such as three dimensional imaging of regulatory domains and of the anatomy of regulatory complexes
  • In vivo selection and amplification systems
  • Advances in allogeneic transplantation, with improved immune suppression
  • Catalyzing preclinical development, e.g., pharmacokinetics, preclinical toxicology
  • Myeloablation studies
  • Hemoglobin F assays in unrelated clinical drug trials

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Last Reviewed: November 22, 2013