Treating sickle cell disease by targeting HbS polymerization

Blood

Volumn 129, Issue 20, 2017, Pages 2719-2726

  Eaton, William A ^a   Bunn, H Franklin ^b  

^a NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,3 DIPHOSPHOGLYCERIC ACID; ANTISICKLING AGENT; HEMOGLOBIN F; HEMOGLOBIN S; OXYGEN;

CLINICAL TRIAL (TOPIC); HEMOGLOBIN DETERMINATION; HEMOGLOBIN SYNTHESIS; HUMAN; NONHUMAN; OXYGEN AFFINITY; POLYMERIZATION; PRIORITY JOURNAL; REVIEW; SICKLE CELL ANEMIA; ANEMIA, SICKLE CELL; ANIMAL; BIOSYNTHESIS; METABOLISM;

ANEMIA, SICKLE CELL; ANIMALS; CLINICAL TRIALS AS TOPIC; FETAL HEMOGLOBIN; HEMOGLOBIN, SICKLE; HUMANS; OXYGEN; POLYMERIZATION;

EID: 85019675999     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2017-02-765891     Document Type: Review

References (108)

1. Ataga KI, Stocker J. The trials and hopes for drug development in sickle cell disease. Br J Haematol. 2015;170(6): 768-780.
2. Gavini N, Hoots WK, Mensah GA, Hanspal M. An analysis of the NIH-supported sickle cell disease research portfolio. Blood Cells Mol Dis. 2015;54(2): 198-205.
3. Telen MJ. Beyond hydroxyurea: new and old drugs in the pipeline for sickle cell disease. Blood. 2016;127(7):810-819.
4. Kato GJ. New insights into sickle cell disease: mechanisms and investigational therapies. Curr Opin Hematol. 2016;23(3):224-232.
5. Archer N, Galacteros F, Brugnara C. 2015 Clinical trials update in sickle cell anemia. Am J Hematol. 2015;90(10):934-950.
6. Pauling L, Itano HA, Singer SJ, Wells IC. Sickle cell anemia a molecular disease. Science. 1949; 110(2865):543-548.
7. Eaton WA. Linus Pauling and sickle cell disease. Biophys Chem. 2003;100(1-3):109-116.
8. Hsieh MM, Fitzhugh CD, Tisdale JF. Allogeneic hematopoietic stem cell transplantation for sickle cell disease: the time is now. Blood. 2011;118(5): 1197-1207.
9. Robinson TM, Fuchs EJ. Allogeneic stem cell transplantation for sickle cell disease. Curr Opin Hematol. 2016;23(6):524-529.
10. Lettre G, Bauer DE. Fetal haemoglobin in sicklecell disease: from genetic epidemiology to new therapeutic strategies. Lancet. 2016;387(10037): 2554-2564.
11. Canver MC, Orkin SH. Customizing the genome as therapy for the b-hemoglobinopathies. Blood. 2016;127(21):2536-2545.
12. Ribeil JA, Hacein-Bey-Abina S, Payen E, et al. Gene therapy in a patient with sickle cell disease. N Engl J Med. 2017;376(9):848-855.
13. McGann PT, Hernandez AG, Ware RE. Sickle cell anemia in sub-Saharan Africa: advancing the clinical paradigm through partnerships and research. Blood. 2017;129(2):155-161.
14. Platt OS, Orkin SH, Dover G, Beardsley GP, Miller B, Nathan DG. Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia. J Clin Invest. 1984;74(2):652-656.
15. Charache S, Terrin ML, Moore RD, et al; Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med. 1995;332(20): 1317-1322.
16. Ware RE. Optimizing hydroxyurea therapy for sickle cell anemia. Hematology Am Soc Hematol Educ Program. 2015;2015:436-443.
17. Hebbel RP, Boogaerts MA, Eaton JW, Steinberg MH. Erythrocyte adherence to endothelium in sickle-cell anemia. A possible determinant of disease severity. N Engl J Med. 1980;302(18): 992-995.
18. Hebbel RP, Yamada O, Moldow CF, Jacob HS, White JG, Eaton JW. Abnormal adherence of sickle erythrocytes to cultured vascular endothelium: possible mechanism for microvascular occlusion in sickle cell disease. J Clin Invest. 1980;65(1):154-160.
19. Frenette PS, Atweh GF. Sickle cell disease: old discoveries, new concepts, and future promise. J Clin Invest. 2007;117(4):850-858.
20. Kato GJ, Gladwin MT, Steinberg MH. Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes. Blood Rev. 2007;21(1): 37-47.
21. Nath KA, Hebbel RP. Sickle cell disease: renal manifestations and mechanisms. Nat Rev Nephrol. 2015;11(3):161-171.
22. Telen MJ, Wun T, McCavit TL, et al. Randomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use. Blood. 2015; 125(17):2656-2664.
23. Ataga KI, Kutlar A, Kanter J, et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017;376(5):429-439.
24. Greenberg J, Ohene-Frempong K, Halus J, Way C, Schwartz E. Trial of low doses of aspirin as prophylaxis in sickle cell disease. J Pediatr. 1983;102(5):781-784.
25. Orringer EP, Casella JF, Ataga KI, et al. Purified poloxamer 188 for treatment of acute vasoocclusive crisis of sickle cell disease: A randomized controlled trial. JAMA. 2001; 286(17):2099-2106.
26. Schnog JB, Kater AP, Mac Gillavry MR, et al. Low adjusted-dose acenocoumarol therapy in sickle cell disease: a pilot study. Am J Hematol. 2001;68(3):179-183.
27. Ataga KI, Key NS. Hypercoagulability in sickle cell disease: new approaches to an old problem. Hematology Am Soc Hematol Educ Program. 2007:91-96.
28. Ataga KI, Reid M, Ballas SK, et al; ICA- 17043-10 Study Investigators. Improvements in haemolysis and indicators of erythrocyte survival do not correlate with acute vaso-occlusive crises in patients with sickle cell disease: a phase III randomized, placebo-controlled, double-blind study of the Gardos channel blocker senicapoc (ICA-17043). Br J Haematol. 2011;153(1): 92-104.
29. Gladwin MT, Kato GJ, Weiner D, et al; DeNOVO Investigators. Nitric oxide for inhalation in the acute treatment of sickle cell pain crisis: a randomized controlled trial. JAMA. 2011;305(9): 893-902.
30. Machado RF, Barst RJ, Yovetich NA, et al; walk-PHaSST Investigators and Patients. Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity. Blood. 2011;118(4): 855-864.
31. Desai PC, Brittain JE, Jones SK, et al. A pilot study of eptifibatide for treatment of acute pain episodes in sickle cell disease. Thromb Res. 2013;132(3):341-345.
32. Heeney MM, Hoppe CC, Abboud MR, et al; DOVE Investigators. A multinational trial of prasugrel for sickle cell vaso-occlusive events. N Engl J Med. 2016;374(7):625-635.
33. Bunn HF, Forget BG. Hemoglobin: Molecular, Genetic and Clinical Aspects. Philadelphia, PA: W.B. Saunders; 1984.
34. Mozzarelli A, Hofrichter J, Eaton WA. Delay time of hemoglobin S polymerization prevents most cells from sickling in vivo. Science. 1987; 237(4814):500-506.
35. Eaton WA, Hofrichter J. Sickle cell hemoglobin polymerization. Adv Protein Chem. 1990;40: 63-279.
36. Poillon WN, Kim BC, Rodgers GP, Noguchi CT, Schechter AN. Sparing effect of hemoglobin F and hemoglobin A2 on the polymerization of hemoglobin S at physiologic ligand saturations. Proc Natl Acad Sci USA. 1993;90(11): 5039-5043.
37. Steinberg MH, Chui DHK, Dover GJ, Sebastiani P, Alsultan A. Fetal hemoglobin in sickle cell anemia: a glass half full? Blood. 2014;123(4): 481-485.
38. Hofrichter J, Ross PD, Eaton WA. Kinetics and mechanism of deoxyhemoglobin S gelation: a new approach to understanding sickle cell disease. Proc Natl Acad Sci USA. 1974;71(12): 4864-4868.
39. Ferrone FA. The delay time in sickle cell disease after 40 years: A paradigm assessed. Am J Hematol. 2015;90(5):438-445.
40. Ferrone FA, Hofrichter J, Eaton WA. Kinetics of sickle hemoglobin polymerization. I. Studies using temperature-jump and laser photolysis techniques. J Mol Biol. 1985;183(4):591-610.
41. Christoph GW, Hofrichter J, Eaton WA. Understanding the shape of sickled red cells. Biophys J. 2005;88(2):1371-1376.
42. Noguchi CT, Torchia DA, Schechter AN. Intracellular polymerization of sickle hemoglobin. Effects of cell heterogeneity. J Clin Invest. 1983; 72(3):846-852.
43. Eaton WA, Hofrichter J. Hemoglobin S gelation and sickle cell disease. Blood. 1987;70(5): 1245-1266.
44. Eaton WA, Hofrichter J, Ross PD. Editorial: Delay time of gelation: a possible determinant of clinical severity in sickle cell disease. Blood. 1976;47(4):621-627.
45. Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med. 1997;337(11): 762-769.
46. Dykes G, Crepeau RH, Edelstein SJ. Threedimensional reconstruction of the fibres of sickle cell haemoglobin. Nature. 1978;272(5653): 506-510.
47. Wishner BC, Ward KB, Lattman EE, Love WE. Crystal structure of sickle-cell deoxyhemoglobin at 5 A resolution. J Mol Biol. 1975;98(1):179-194.
48. Benesch RE, Kwong S, Benesch R, Edalji R. Location and bond type of intermolecular contacts in the polymerisation of haemoglobin S. Nature. 1977;269(5631):772-775.
49. Nagel RL, Johnson J, Bookchin RM, et al. Betachain contact sites in the haemoglobin S polymer. Nature. 1980;283(5750):832-834.
50. Shan Y, Kim ET, Eastwood MP, Dror RO, Seeliger MA, Shaw DE. How does a drug molecule find its target binding site? J Am Chem Soc. 2011;133(24):9181-9183.
51. Charache S, Barton FB, Moore RD, et al; The Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive "switching" agent. Medicine (Baltimore). 1996;75(6): 300-326.
52. Goldberg MA, Brugnara C, Dover GJ, Schapira L, Charache S, Bunn HF. Treatment of sickle cell anemia with hydroxyurea and erythropoietin. N Engl J Med. 1990;323(6):366-372.
53. Bauer DE, Kamran SC, Orkin SH. Reawakening fetal hemoglobin: prospects for new therapies for the b-globin disorders. Blood. 2012;120(15): 2945-2953.
54. Sankaran VG, Menne TF, Xu J, et al. Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A. Science. 2008;322(5909):1839-1842.
55. Xu J, Peng C, Sankaran VG, et al. Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing. Science. 2011; 334(6058):993-996.
56. Eaton WA, Hofrichter J. The biophysics of sickle cell hydroxyurea therapy. Science. 1995; 268(5214):1142-1143.
57. Bunn HF, McDonough M. Asymmetrical hemoglobin hybrids. An approach to the study of subunit interactions. Biochemistry. 1974;13(5): 988-993.
58. Goldberg MA, Husson MA, Bunn HF. Participation of hemoglobins A and F in polymerization of sickle hemoglobin. J Biol Chem. 1977;252(10):3414-3421.
59. Minton AP. Non-ideality and the thermodynamics of sickle-cell hemoglobin gelation. J Mol Biol. 1977;110(1):89-103.
60. Benesch RE, Edalji R, Benesch R, Kwong S. Solubilization of hemoglobin S by other hemoglobins. Proc Natl Acad Sci USA. 1980; 77(9):5130-5134.
61. Ross PD, Minton AP. Analysis of non-ideal behavior in concentrated hemoglobin solutions. J Mol Biol. 1977;112(3):437-452.
62. Sunshine HR, Hofrichter J, Eaton WA. Gelation of sickle cell hemoglobin in mixtures with normal adult and fetal hemoglobins. J Mol Biol. 1979; 133(4):435-467.
63. Ferrone FA, Hofrichter J, Eaton WA. Kinetics of sickle hemoglobin polymerization. II. A double nucleation mechanism. J Mol Biol. 1985;183(4): 611-631.
64. Cellmer T, Ferrone FA, Eaton WA. Universality of supersaturation in protein-fiber formation. Nat Struct Mol Biol. 2016;23(5):459-461.
65. Monod J, Wyman J, Changeux JP. On the nature of allosteric transitions: a plausible model. J Mol Biol. 1965;12(1):88-118.
66. Eaton WA, Henry ER, Hofrichter J, Mozzarelli A. Is cooperative oxygen binding by hemoglobin really understood? Nat Struct Biol. 1999;6(4): 351-358.
67. Bertles JF, Rabinowitz R, Döbler J. Hemoglobin interaction: modification of solid phase composition in the sickling phenomenon. Science. 1970;169(3943):375-377.
68. Ross PD, Hofrichter J, Eaton WA. Thermodynamics of gelation of sickle cell deoxyhemoglobin. J Mol Biol. 1977;115(2): 111-134.
69. Sunshine HR, Hofrichter J, Ferrone FA, Eaton WA. Oxygen binding by sickle cell hemoglobin polymers. J Mol Biol. 1982;158(2):251-273.
70. Henry ER, Mozzarelli A, Viappiani C, et al. Experiments on hemoglobin in single crystals and silica gels distinguish among allosteric models. Biophys J. 2015;109(6):1264-1272.
71. Padlan EA, Love WE. Refined crystal structure of deoxyhemoglobin S. II. Molecular interactions in the crystal. J Biol Chem. 1985;260(14): 8280-8291.
72. Beutler E. The effect of methemoglobin formation in sickle cell disease. J Clin Invest. 1961;40(10):1856-1871.
73. Beutler E. The effect of carbon monoxide on red cell life span in sickle cell disease. Blood. 1975; 46(2):253-259.
74. Abraham DJ, Mehanna AS, Wireko FC, Whitney J, Thomas RP, Orringer EP. Vanillin, a potential agent for the treatment of sickle cell anemia. Blood. 1991;77(6):1334-1341.
75. Benesch R, Benesch RE. Intracellular organic phosphates as regulators of oxygen release by haemoglobin. Nature. 1969;221(5181):618-622.
76. Bunn HF, Jandl JH. Control of hemoglobin function within the red cell. N Engl J Med. 1970; 282(25):1414-1421.
77. Bunn HF. Evolution of mammalian hemoglobin function. Blood. 1981;58(2):189-197.
78. Perutz MF. The Bohr effect and combination with organic phosphates. Nature. 1970;228(5273): 734-739.
79. Bunn HF, Briehl RW. The interaction of 2,3- diphosphoglycerate with various human hemoglobins. J Clin Invest. 1970;49(6): 1088-1095.
80. Beutler E, Paniker NV, West C. The effect of 2,3-DPG on the sickling phenomenon. Blood. 1971;37(2):184-186.
81. Poillon WN, Kim BC. 2,3-Diphosphoglycerate and intracellular pH as interdependent determinants of the physiologic solubility of deoxyhemoglobin S. Blood. 1990;76(5): 1028-1036.
82. Hofrichter J, Ross PD, Eaton WA. Supersaturation in sickle cell hemoglobin solutions. Proc Natl Acad Sci USA. 1976; 73(9):3035-3039.
83. Poillon WN, Kim BC, Labotka RJ, Hicks CU, Kark JA. Antisickling effects of 2,3- diphosphoglycerate depletion. Blood. 1995; 85(11):3289-3296.
84. Cohen-Solal M, Préhu C, Wajcman H, et al. A new sickle cell disease phenotype associating Hb S trait, severe pyruvate kinase deficiency (PK Conakry), and an alpha2 globin gene variant (Hb Conakry). Br J Haematol. 1998;103(4):950-956.
85. Alli N, Coetzee M, Louw V, et al. Sickle cell disease in a carrier with pyruvate kinase deficiency. Hematology. 2008;13(6):369-372.
86. Rose ZB, Liebowitz J. 2,3-diphosphoglycrate phosphatase from human erythrocytes. General properties and activation by anions. J Biol Chem. 1970;245(12):3232-3241.
87. Rose ZB. A procedure for decreasing the level of 2,3-bisphosphoglycerate in red cells in vitro. Biochem Biophys Res Commun. 1976;73(4): 1011-1017.
88. Ponder E. The tonicity-volume relations for systems containing human red cells and the chlorides of monovalent cations. J Gen Physiol. 1949;32(3):391-398.
89. Sunshine HR, Hofrichter J, Eaton WA. Requirement for therapeutic inhibition of sickle haemoglobin gelation. Nature. 1978;275(5677): 238-240.
90. Rosa RM, Bierer BE, Thomas R, et al. A study of induced hyponatremia in the prevention and treatment of sickle-cell crisis. N Engl J Med. 1980;303(20):1138-1143.
91. Das N, Xie L, Ramakrishnan SK, Campbell A, Rivella S, Shah YM. Intestine-specific disruption of hypoxia-inducible factor (HIF)-2 alpha improves anemia in sickle cell disease. J Biol Chem. 2015;290(39):23523-23527.
92. Castro O, Poillon WN, Finke H, Massac E. Improvement of sickle cell anemia by iron-limited erythropoiesis. Am J Hematol. 1994;47(2):74-81.
93. Stocker JW, De Franceschi L, McNaughton- Smith GA, Corrocher R, Beuzard Y, Brugnara C. ICA-17043, a novel Gardos channel blocker, prevents sickled red blood cell dehydration in vitro and in vivo in SAD mice. Blood. 2003; 101(6):2412-2418.
94. Ataga KI, Smith WR, De Castro LM, et al; ICA- 17043-05 Investigators. Efficacy and safety of the Gardos channel blocker, senicapoc (ICA- 17043), in patients with sickle cell anemia. Blood. 2008;111(8):3991-3997.
95. Clark MR, Mohandas N, Shohet SB. Hydration of sickle cells using the sodium ionophore Monensin. A model for therapy. J Clin Invest. 1982;70(5):1074-1080.
96. Li Q, Henry ER, Hofrichter J, et al. Kinetic assay shows that increasing red cell volume could be a treatment for sickle cell disease. Proc Natl Acad Sci USA. 2017;114(5):E689-E696.
97. Wambebe C, Khamofu H, Momoh JAF, et al. Double-blind, placebo-controlled, randomised cross-over clinical trial of NIPRISAN in patients with Sickle Cell Disorder. Phytomedicine. 2001; 8(4):252-261.
98. Wambebe CO, Bamgboye EA, Badru BO, et al. Efficacy of niprisan in the prophylactic management of patients with sickle cell disease. Curr Ther Res. 2001;62(1):26-34.
99. Iyamu EW, Turner EA, Asakura T. In vitro effects of NIPRISAN (Nix-0699): a naturally occurring, potent antisickling agent. Br J Haematol. 2002; 118(1):337-343.
100. Iyamu EW, Turner EA, Asakura T. Niprisan (Nix- 0699) improves the survival rates of transgenic sickle cell mice under acute severe hypoxic conditions. Br J Haematol. 2003;122(6): 1001-1008.
101. Swift R, Abdulmalik O, Chen Q, et al. SCD-101: A new anti-sickling drug reduces pain and fatigue and improves red blood cell shape in peripheral blood of patients with sickle cell disease [abstract]. Blood. 2016;128(22). Abstract 121.
102. Abdulmalik O, Safo MK, Chen Q, et al. 5- hydroxymethyl-2-furfural modifies intracellular sickle haemoglobin and inhibits sickling of red blood cells. Br J Haematol. 2005;128(4): 552-561.
103. van Beers EJ, Samsel L, Mendelsohn L, et al. Imaging flow cytometry for automated detection of hypoxia-induced erythrocyte shape change in sickle cell disease. Am J Hematol. 2014;89(6): 598-603.
104. Oder E, Safo MK, Abdulmalik O, Kato GJ. New developments in anti-sickling agents: can drugs directly prevent the polymerization of sickle haemoglobin in vivo? Br J Haematol. 2016; 175(1):24-30.
105. Metcalf B, Chuang C, Dufu K, et al. Discovery of GBT440, an orally bioavailable R-state stabilizer of sickle cell hemoglobin. ACS Med Chem Lett. 2017;8(3):321-326.
106. Hutchaleelaha A, Patel M, Silva A, Oksenberg D, Metcalf B. GBT440 demonstrates high specificity for red blood cells in nonclinical species [abstract]. Blood. 2015;126(23). Abstract 2172.
107. Lehrer-Graiwer J, Howard J, Hemmaway CJ, et al. GBT440, a potent anti-sickling hemoglobin modifier reduces hemolysis, improves anemia and nearly eliminates sickle cells in peripheral blood of patients with sickle cell disease [abstract]. Blood. 2015;126(23). Abstract 542.
108. Lehrer-Graiwer J, Howard J, Hemmaway CJ, et al. Long-term dosing in sickle cell disease subjects with GBT440, a novel HbS polymerization inhibitor [abstract]. Blood. 2016; 128(22). Abstract 2488.