Advances in Sickle Cell Disease Treatments

2020 ◽  
Vol 27 ◽  
Author(s):  
Aline Renata Pavan ◽  
Jean Leandro dos Santos
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Low Income ◽  
New Drugs ◽  
Low Income Countries ◽  
High Morbidity ◽  
Single Mutation ◽  
Cell Disease ◽  
Hematopoietic Stem ◽  
Therapeutic Alternatives

: Sickle Cell Disease (SCD) is an inherited disorder of red blood cells that is caused by a single mutation in the βglobin gene. The disease, which afflicts millions of patients worldwide mainly in low income countries, is characterized by high morbidity, mortality and low life expectancy. The new pharmacological and non-pharmacological strategies for SCD is urgent in order to promote treatments able to reduce patient’s suffering and improve their quality of life. Since the FDA approval of HU in 1998, there have been few advances in discovering new drugs; however, in the last three years voxelotor, crizanlizumab, and glutamine have been approved as new therapeutic alternatives. In addition, new promising compounds have been described to treat the main SCD symptoms. Herein, focusing on drug discovery, we discuss new strategies to treat SCD that have been carried out in the last ten years to discover new, safe, and effective treatments. Moreover, nonpharmacological approaches, including red blood cell exchange, gene therapy and hematopoietic stem cell transplantation will be presented.

Sickle cell disease has emerged as a public health concern. Some drugs may conflict with curative therapies, yet they may be useful as a bridge to HSCT and gene therapy

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Low Income ◽  
Low Income Countries ◽  
Health Concern ◽  
Haematopoietic Stem Cell ◽  
Cell Disease ◽  
Public Health Concern ◽  
Disease Modifying Drugs ◽  
Matched Sibling

Sickle cell disease has resurfaced as a health-care priority in high-income nations and low-income countries (LMICs). Transplantation results with haploidentical haematopoietic stem cell transplantation (HSCT) are improving, increasing the likelihood of a curative treatment for the majority of patients. The indications for HSCT and for disease-modifying drugs, for example, must be determined. There are still a few things to think about, including biomarkers for systemic vasculopathy. Some medications may compete with curative treatments, but they might potentially be an important bridge treatment to HSCT. One of the most difficult hurdles yet ahead is reaching out to general practitioners and haematologists to bridge the awareness gap about curative alternatives such as matched sibling donor HSCT so that patients and their families may be identified early.

scholarly journals SICKLE CELL DISEASE AND INFECTIONS IN HIGH- AND LOW-INCOME COUNTRIES

2019 ◽  
Vol 11 (1) ◽  
pp. 02019042 ◽  
Author(s):  
Giovanna Cannas
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Host Defense ◽  
Low Income ◽  
Defense Mechanisms ◽  
Developed Countries ◽  
Infectious Complications ◽  
Low Income Countries ◽  
Cell Disease ◽  
Salmonella Infections

Infections, especially pneumococcal septicemia, meningitis, and Salmonella osteomyelitis, are a major cause of morbidity and mortality in patients with sickle cell disease (SCD). SCD increased susceptibility to infection, while infection leads to SCD-specific pathophysiological changes. The risk of infectious complications is highest in children with a palpable spleen before 6 months of age. Functional splenectomy, the results of repeated splenic infarctions, appears to be an important host-defense defect. Infection is the leading cause of death, particularly in less developed countries. Defective host-defense mechanisms enhance the risk of pneumococcal complications. Susceptibility to Salmonella infections can be explained at least in part by a similar mechanism. In high-income countries, the efficacy of the pneumococcal vaccine has been demonstrated in this disease. A decreased in infection incidence has been noted in SCD patients treated prophylactically with daily oral penicillin. Studies in low-income countries suggest the involvement of a different spectrum of etiological agents.

scholarly journals NEW THERAPEUTIC OPTIONS FOR THE TREATMENT OF SICKLE CELL DISEASE

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Alessandro Matte ◽  
Filippo Mazzi ◽  
Enrica Federti ◽  
Oliviero Olivieri ◽  
Lucia De Franceschi
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Therapeutic Strategies ◽  
Therapeutic Options ◽  
High Morbidity ◽  
Novel Therapies ◽  
Cell Disease ◽  
Hematopoietic Stem ◽  
Positive Effects ◽  
Cell Dehydration

Sickle cell disease (SCD; ORPHA232; OMIM # 603903) is a chronic and invalidating disorder distributed worldwide, with high morbidity and mortality.  Given the disease complexity and the multiplicity of pathophysiological targets, development of new therapeutic options is critical, despite the positive effects of hydroxyurea (HU), for many years the only approved drug for SCD. New therapeutic strategies might be divided into (1) pathophysiology-related novel therapies and (2) innovations in curative therapeutic options such as hematopoietic stem cell transplantation and gene therapy. The pathophysiology related novel therapies are: a) Agents which reduce sickling or prevent sickle red cell dehydration; b) Agents targeting SCD vasculopathy and sickle cell-endothelial adhesive events; c) Anti-oxidant agents. This review highlights new therapeutic strategies in SCD and discusses future developments, research implications, and possible innovative clinical trials.  

scholarly journals RH genotyping in a sickle cell disease patient contributing to hematopoietic stem cell transplantation donor selection and management

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 2836-2838 ◽  
Author(s):  
Ross M. Fasano ◽  
Alessandro Monaco ◽  
Emily Riehm Meier ◽  
Philippe Pary ◽  
A. Hallie Lee-Stroka ◽  
...  
Keyword(s):  
Stem Cell ◽  
Sickle Cell Disease ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Blood Group ◽  
Sickle Cell ◽  
Disease Patient ◽  
Nucleotide Sequencing ◽  
Cell Disease ◽  
Hematopoietic Stem

Abstract African individuals harbor molecular RH variants, which permit alloantibody formation to high-prevalence Rh antigens after transfusions. Genotyping identifies such RH variants, which are often missed by serologic blood group typing. Comprehensive molecular blood group analysis using 3 genotyping platforms, nucleotide sequencing, and serologic evaluation was performed on a 7-year-old African male with sickle cell disease who developed an “e-like” antibody shortly after initiating monthly red blood cell (RBC) transfusions for silent stroke. Genotyping of the RH variant predicted a severe shortage of compatible RBCs for long-term transfusion support, which contributed to the decision for hematopoetic stem cell transplantation. RH genotyping confirmed the RH variant in the human leukocyte antigen–matched sibling donor. The patient's (C)ces type 1 haplotype occurs in up to 11% of African American sickle cell disease patients; however, haplotype-matched RBCs were serologically incompatible. This case documents that blood unit selection should be based on genotype rather than one matching haplotype.

Demands and challenges for patients with sickle-cell disease requiring hematopoietic stem cell transplantation in Saudi Arabia

2016 ◽  
Vol 20 (6) ◽  
pp. 831-835 ◽  
Author(s):  
Abdulrahman Alsultan ◽  
Wasil Jastaniah ◽  
Sameera Al Afghani ◽  
Muneer H. Al Bagshi ◽  
Zaki Nasserullah ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Stem Cell ◽  
Sickle Cell Disease ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Sickle Cell ◽  
Cell Disease ◽  
Hematopoietic Stem

scholarly journals 115. Correction of the Sickle-Cell Disease Mutation in Human Hematopoietic Stem/Progenitor Cells

2015 ◽  
Vol 23 ◽  
pp. S48
Author(s):  
Megan D. Hoban ◽  
Matthew C. Mendel ◽  
Zulema Romero ◽  
Michael L. Kaufman ◽  
Alok V. Joglekar ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Progenitor Cells ◽  
Sickle Cell ◽  
Cell Disease ◽  
Hematopoietic Stem ◽  
Disease Mutation

Sickle Cell Disease Hematopoietic Stem Cell gene therapy with globin gene addition is promising

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Therapy ◽  
Stem Cell ◽  
Sickle Cell Disease ◽  
Hematopoietic Stem Cell ◽  
Sickle Cell ◽  
Globin Gene ◽  
Autologous Transplantation ◽  
Gene Repair ◽  
Cell Disease ◽  
Hematopoietic Stem

Autologous transplantation of gene-modified HSCs might be used to treat Sickle Cell Disease (SCD) once and for all. Hematopoietic Stem Cell (HSC) gene therapy with lentiviral-globin gene addition was optimized by HSC collection, vector constructs, lentiviral transduction, and conditioning in the current gene therapy experiment for SCD, resulting in higher gene marking and phenotypic correction. Further advancements over the next decade should allow for a widely approved gene-addition therapy. Long-term engraftment is crucial for gene-corrected CD34+ HSCs, which might be addressed in the coming years, and gene repair of the SCD mutation in the-globin gene can be achieved in vitro using genome editing in CD34+ cells. Because of breakthroughs in efficacy, safety, and delivery strategies, in vivo gene addition and gene correction in BM HSCs is advancing. Overall, further research is needed, but HSC-targeted gene addition/gene editing therapy is a promising SCD therapy with curative potential that might be widely available soon.

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