Sickle cell disease (SCD), iNKT cells, and regadenoson infusion. Trans Am Clin Climatol Assoc 2012;123:312-7; discussion 317-8
Date
01/11/2013Pubmed ID
23303999Pubmed Central ID
PMC3540605Scopus ID
2-s2.0-84879475046 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
A humanized murine sickle cell-disease (SCD) model (NY1DD) has been used to study ischemia/reperfusion injury (IRI) in sickle cell anemia, and iNKT cells (a very small subset of murine and human T cells) have been found to instigate such injury in this model. Furthermore, levels of activated iNKT cells are generally elevated in the circulation of patients with SCD. Because activated iNKT cells are rich in adenosine A2A receptors which, when agonized, down-regulate the inflammatory cytokine expression that characterizes the cells, we have conducted a phase 1 trial of a constant infusion of low-dose regadenoson (an adenosine analogue with high A2A receptor specificity) to determine its safety and the capacity of a safe dose to down-regulate circulating iNKT cells in patients with SCD. We have found two dose rates that are both safe and effective and now plan a controlled Phase 2B clinical trial to determine whether our highest dose, administered as a 48-hour constant infusion, will induce faster remission in both painful vaso-occlusive crisis (pVOC) and acute chest syndrome (ACS).
Author List
Nathan DG, Field J, Lin G, Neuberg D, Majerus E, Onyekwere O, Keefer J, Okam M, Ross A, Linden JAuthor
Joshua J. Field MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adenosine A2 Receptor AgonistsAnemia, Sickle Cell
Cell Count
Dose-Response Relationship, Drug
Humans
Infusions, Intravenous
Natural Killer T-Cells
Purines
Pyrazoles
Remission Induction
Time Factors
Treatment Outcome