Advances in managing sickle cell anemia: a systematic review
DOI:
https://doi.org/10.51412/psnnjp.2024.06Keywords:
Acute chest syndrome, Gene therapy, Haemoglobin, Sickle cell anemia, Vaso-occlusion, NiprisanAbstract
Background: Despite the acceptance and approval of several medications and techniques to reduce vaso-occlusive episodes (VOEs), Hydroxyurea along with other analgesics have remained the primary treatment option for Sickle Cell Anaemia (SCA) in Nigeria. However, in terms of cost-effectiveness and fewer side effects, Niprisan® remains the preferred option. In this review, we discussed new drugs/technologies as well as previously approved medications that could ameliorate SCAaside from the options available in Nigeria; and we hope to inspire our readers by providing insights into new inventions to overcome current challenges in the field.
Methods: This review involved a comprehensive examination of existing literature on SCA treatments; specifically focusing on new pharmaceutical developments, innovative technologies, and previously approved medications on Google Scholar, PubMed, ResearchGate, EMBASE, and Cochrane database using SCA, novel therapies, Niprisan®, haematopoietic stem cell transplant, and gene therapy as search items. Additionally, the references of some retrieved articles were also searched. The literature retrieved included review articles, meta-analyses, clinical trials, and original research papers.
Conclusions: Advanced insights into the cellular and molecular basis of the sickle cell disease processes have unveiled several established/potential drug targets on which newer SCA therapies are based. These newer therapies have varied mechanisms ranging from Fetal haemoglobin (HbF) induction, RBC membrane stabilization, oxidative stress reduction, adhesion inhibition, reduction of inflammation, prevention of polymerization, and enhanced flow dynamics to gene-directed therapies with the potential for cure. This expounded review has highlighted real progress in SCA treatment. However, an improved survival rate will depend on the participation of clinical sites across the globe, as well as the availability of funds to support studies needed to confirm the safety and efficacy of these
drugs.
References
Kavanagh PL, Fasipe TA, Wun T. Sickle Cell Disease: A Review. JAMA. 2022 Jul 5;328(1):57-68. doi: 10.1001/jama.2022.10233.
Piel FB, Steinberg MH, Rees DC. Sickle Cell Disease. NEnglJ Med. 2017 Apr 20; 376 (16): 1561-1573.doi:10.1056/NEJMra1510865.
Adigwe OP, Onavbavba G, Onoja SO. Impact of Sickle Cell Disease on Affected Individuals in Nigeria: A Critical Review. Int J Gen Med. 2023
Aug 14; 16: 3503- 3515. doi: 10.2147/IJGM.S410015.
Schroeder P, Fulzele K, Forsyth S, Ribadeneira MD, Guichard S, Wilker E, Marshall CG, Drake A, Fessler R, Konstantinidis DG, Seu KG, Kalfa
TA. Etavopivat, a Pyruvate Kinase Activator in Red Blood Cells, for the Treatment of Sickle Cell Dis e a s e . J Pha rma col Exp The r. 2022
M a r ; 3 8 0 ( 3 ) : 2 1 0 - 2 1 9 . d o i : 10.1124/jpet.121.000743. Epub 2022 Jan 14.
Owusu-Ansah A, Ihunnah CA, Walker AL, OforiAcquah SF. Inflammatory targets of therapy in si ckl e c e ll dis e a s e . Tr ansl Re s. 2016
J a n ; 1 6 7 ( 1 ) : 2 8 1 - 9 7 . d o i : 10.1016/j.trsl.2015.07.001. Epub 2015 Jul 11.
Vona R, Sposi NM, Mattia L, Gambardella L, Straface E, Pietraforte D. Sickle Cell Disease: Role of Oxidative Stress and Antioxidant Therapy.
Antioxidants (Basel). 2021 Feb 16;10(2):296. doi: 10.3390/antiox10020296.
Telen MJ. Beyond hydroxyurea: new and old drugs in the pipeline for sickle cell disease. Blood. 2016 Feb 18;127(7):810-9. doi: 10.1182/blood2015-09-618553. Epub 2016 Jan 12.
Ameh SJ, Obodozie OO, Afolabi EK, Oyedele EO, Ache TA, Onanuga C. Some basic requirements for preparing an antisickling herbal medicine. Int J Pharm Pharmacol.2012 3(1):001-0 0 6 . https://doi.org/10.3109/19390210903534988
Iyamu EW, Turner EA, Asakura T. Niprisan (Nix0699) improves the survival rates of transgenic sickle cell mice under acute severe hypoxic
c o n d i t i o n s . B r J H a e m a t o l . 2 0 0 3 Sep;122(6):1001-8. doi: 10.1046/j.
Perampaladas K, Masum H, Kapoor A, Shah R, D a a r A S , S i n g e r PA . T h e r o a d t o commercialization in Africa: lessons from
developing the sickle-cell drug Niprisan. BMC Int Health Hum Rights. 2010 Dec 13;10 Suppl 1(Suppl 1):S11. doi: 10.1186/1472-698X-10-S1-
S11.
Nwabuko OC, Onwuchekwa U, Iheji O. An overview of sickle cell disease from the sociodemographic triangle - a Nigerian singleinstitution retrospective study. Pan Afr Med J. 2 0 2 2 F e b 2 3 ; 4 1 : 1 6 1 . d o i : 10.11604/pamj.2022.41.161.27117.
Galadanci N, Wudil BJ, Balogun TM, Ogunrinde GO, Akinsulie A, Hasan-Hanga F, Mohammed AS, Kehinde MO, Olaniyi JA, Diaku-Akinwumi IN, Brown BJ, Adeleke S, Nnodu OE, Emodi I, Ahmed S, Osegbue AO, Akinola N, Opara HI, Adegoke SA, Aneke J, Adekile AD. Current sickle
cell disease management practices in Nigeria. Int H e a lt h . 2 0 1 4 M a r ; 6 ( 1 ) : 2 3 - 8 . d o i: 10.1093/inthealth/iht022. Epub 2013 Oct 10
George A, Pushkaran S, Konstantinidis DG, Koochaki S, Malik P, Mohandas N, Zheng Y, Joiner CH, Kalfa TA. Erythrocyte NADPH
oxidase activity modulated by Rac GTPases, PKC, and plasma cytokines contributes to oxidative stress in sickle cell disease. Blood. 2013
Mar 14;121(11):2099-107. doi: 10.1182/blood2012-07-441188. Epub 2013 Jan 24. Erratum in: Blood. 2014 Mar 20;123(12):1972.
ichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A, Hassab H, Achebe MM, Alkindi S, Brown RC, Diuguid DL, Telfer P,
Tsitsikas DA, Elghandour A, Gordeuk VR, Kanter J, Abboud MR, Lehrer-Graiwer J, Tonda M, Intondi A, Tong B, Howard J; HOPE Trial Investigators. A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease. N Engl J Med. 2 0 1 9 A u g 8 ; 3 8 1 ( 6 ) : 5 0 9 - 5 1 9 . d o i: 10.1056/NEJMoa1903212. Epub 2019 Jun 14.
Al-Samkari H, van Beers EJ. Mitapivat, a novel pyruvate kinase activator, for the treatment of hereditary hemolytic anemias. Ther Adv Hematol. 2021 Dec 21;12:20406207211066070. doi: 10.1177/20406207211066070.
Vinchi F, De Franceschi L, Ghigo A, Townes T, Cimino J, Silengo L, Hirsch E, Altruda F, Tolosano E. Hemopexin therapy improves
cardiovascular function by preventing hemeinduced endothelial toxicity in mouse moels of hemolytic diseases. Circulation. 2013 Mar
6 ; 1 2 7 ( 1 2 ) : 1 3 1 7 - 2 9 . d o i : 10.1161/CIRCULATIONAHA.112.130179. Epub 2013 Feb 27.
Coll RC, Robertson AA, Chae JJ, Higgins SC, Muñoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A, Croker DE, Butler MS,
Haneklaus M, Sutton CE, Núñez G, Latz E, Kastner DL, Mills KH, Masters SL, Schroder K, Cooper MA, O'Neill LA. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med. 2015 Mar;21(3):248-55. doi: 10.1038/nm.3806. Epub 2015 Feb 16.
Sun SC. Non-canonical NF-κB signaling pathway. Cell Res. 2011 Jan;21(1):71-85. doi: 10.1038/cr.2010.177. Epub 2010 Dec 21.
Hayden MS, Ghosh S. Regulation of NF-κB by TNF family cytokines. Semin Immunol. 2014 J u n ; 2 6 ( 3 ) : 2 5 3 - 6 6 . d o i : 10.1016/j.smim.2014.05.004. Epub 2014 Jun 21.
Ogunlesi F, Heeney MM, Koumbourlis AC. Systemic corticosteroids in acute chest syndrome: friend or foe? Paediatr Respir Rev. 2014
Mar;15(1):24-7. doi: 10.1016/j.prrv.2013.10.004. Epub 2013 Oct 31.
Pergola C, Gerstmeier J, Mönch B, Çalışkan B, Luderer S, Weinigel C, Barz D, Maczewsky J, Pace S, Rossi A, Sautebin L, Banoglu E, Werz O.
The novel benzimidazole derivative BRP-7 inhibits leukotriene biosynthesis in vitro and in vivo by targeting 5-lipoxygenase-activating
protein (FLAP). Br J Pharmacol. 2014 Jun;171(12):3051-64. doi: 10.1111/bph.12625.
Steinberg MH. Fetal hemoglobin in sickle cell anemia. Blood. 2020 Nov 19;136(21):2392-2400. doi: 10.1182/blood.2020007645.
Komor AC, Zhao KT, Packer MS, Gaudelli NM, Waterbury AL, Koblan LW, Kim YB, Badran AH, Liu DR. Improved base excision repair inhibition
and bacteriophage Mu Gam protein yields C:G-toT:A base editors with higher efficiency and p r o d u c t p u r it y. Sc i A d v. 2 0 1 7 A u g
;3(8):eaao4774. doi: 10.1126/sciadv.aao4774.
Martyn GE, Wienert B, Yang L, Shah M, Norton LJ, Burdach J, Kurita R, Nakamura Y, Pearson RCM, Funnell APW, Quinlan KGR, Crossley M.
Natural regulatory mutations elevate the fetal globin gene via disruption of BCL11A or Z B T B 7 A b i n d i n g . N a t G e n e t. 2 0 1 8 Apr;50(4):498-503. doi: 10.1038/s41588-018-0085-0. Epub 2018 Apr 2.
Mayuranathan T, Newby GA, Feng R, Yao Y, Mayberry KD, Lazzarotto CR, Li Y, Levine RM, Nimmagadda N, Dempsey E, Kang G, Porter SN,
Doerfler PA, Zhang J, Jang Y, Chen J, Bell HW, Crossley M, Bhoopalan SV, Sharma A, Tisdale JF, Pruett-Miller SM, Cheng Y, Tsai SQ, Liu DR,
Weiss MJ, Yen JS. Potent and uniform fetal hemoglobin induction via base editing. Nat Genet. 2023 Jul;55(7):1210-1220. doi: 10.1038/s41588-
-01434-7. Epub 2023 Jul 3.
Li C, Georgakopoulou A, Mishra A, Gil S, Hawkins RD, Yannaki E, Lieber A. In vivo HSPC gene therapy with base editors allows for efficient
reactivation of fetal γ-globin in β-YAC mice. Blood Adv. 2021 Feb 23;5(4):1122-1135. doi: 10.1182/bloodadvances.2020003702.
Kassim AA, Sharma D. Hematopoietic stem cell transplantation for sickle cell disease: The changing landscape. Hematol Oncol Stem Cell
Th e r. 2 0 1 7 D e c ; 1 0 ( 4 ): 2 5 9 - 2 6 6 . d o i: 10.1016/j.hemonc.2017.05.008. Epub 2017 Jun 15.
Wingard JR, Hsu J, Hiemenz JW. Hematopoietic stem cell transplantation: an overview of infection risks and epidemiology. Infect Dis Clin North Am. 2 0 1 0 J u n ; 2 4 ( 2 ) : 2 5 7 - 7 2 . d o i : 10.1016/j.idc.2010.01.010.
Esrick EB, Lehmann LE, Biffi A, Achebe M, Brendel C, Ciuculescu MF, Daley H, MacKinnon B, Morris E, Federico A, Abriss D, Boardman K,
Khelladi R, Shaw K, Negre H, Negre O, Nikiforow S, Ritz J, Pai SY, London WB, Dansereau C, Heeney MM, Armant M, Manis JP, Williams DA. Post-Transcriptional Genetic Silencing of BCL11A to Treat Sickle Cell Disease. N Engl J Med. 2021 Jan 21;384(3):205-215. doi: 10.1056/NEJMoa2029392. Epub 2020 Dec 5.
Frangoul H, Altshuler D, Cappellini MD, Chen YS, Domm J, Eustace BK, Foell J, de la Fuente J, Grupp S, Handgretinger R, Ho TW, Kattamis A,
Kernytsky A, Lekstrom-Himes J, Li AM, Locatelli F, Mapara MY, de Montalembert M, Rondelli D, Sharma A, Sheth S, Soni S, Steinberg MH, Wall D, Yen A, Corbacioglu S. CRISPRCas9 Gene Editing for Sickle Cell Disease and βThalassemia. N Engl J Med. 2021 Jan 2 1 ; 3 8 4 ( 3 ) : 2 5 2 - 2 6 0 . d o i : 10.1056/NEJMoa2031054.
Philippidis A. CASGEVY Makes History as FDAApproves First CRISPR/Cas9 Genome Edited Therapy. Hum Gene Ther. 2024 Jan;35(1-2):1-4.
doi: 10.1089/hum.2023.29263.bfs.
Hua P, Badat M, Hanssen LLP, Hentges LD, Crump N, Downes DJ, Jeziorska DM, Oudelaar AM, Schwessinger R, Taylor S, Milne TA,
Hughes JR, Higgs DR, Davies JOJ. Defining genome architecture at base-pair resolution. Nature. 2021 Jul;595(7865):125-129. doi: 10.1038/s41586-021-03639-4. Epub 2021 Jun 9.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 The Nigerian Journal of Pharmacy
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
