bims-sicedi 2025-07-20 papers

Cardiovasc Hematol Disord Drug Targets. 2025 Jul 14.

Updated Review of Current Therapeutic Approaches for the Management of Sickle Cell Disease.

Devwati Puri, Bhupendra Verma, Harish Bhardwaj, Rajendra Kumar Jangde.

Sickle cell disease is a severe genetic blood disorder marked by the production of abnormal hemoglobin (HbS), leading to sickle-shaped red blood cells that obstruct blood flow and cause various problems, such as the increased risk of infection, persistent anemia, acute pain episodes, and organ damage. Roughly 100,000 Americans suffer from SCD, with approximately 40,000 of them being children. Black people have the highest frequency of the disease. There are six Food and Drug Administration (FDA)-approved drugs, hydroxyurea, L-glutamine, crizanlizumab- TMCA, voxelotor, Casgevy, and Lyfgenia, that are used for the prophylaxis and treatment of serious complications of sickle cell disease. Current treatment approaches focus on symptom management, including pain control, hydroxyurea to reduce pain crises, and transfusions for severe anemia. Based on the clinical trial results, L-glutamine and crizanlizumab-TMCA prevent cell damage and hemoglobin sickling by reducing the sickle cell crisis episodes. At the same time, voxelotor improves hemoglobin oxygen-binding capacity in patients with SCD. Novel therapies, such as gene therapy and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR-Cas9) technology, aim to correct the genetic defect. At the same time, stem cell and bone marrow transplants offer potential cures but are limited by the availability of donors and side effects. Ongoing research seeks to enhance treatment options and develop potential cures for SCD. This review attempts to present a comprehensive overview of the current therapeutic approaches and newly developed innovative medicines to combat and potentially eradicate SCD with an emphasis on their mechanisms, efficacy, and clinical implications.

Keywords: Sickle cell disease; blood transfusion; gene therapy; hemoglobin; hydroxyurea; stem cell transplantation.; vaso-occlusion crisis

DOI: https://doi.org/10.2174/011871529X364941250627090838

Hemasphere. 2025 Jul;9(7): e70167

Reproductive health concerns of women living with sickle cell disease.

Edeghonghon Olayemi.

DOI: https://doi.org/10.1002/hem3.70167

Int J Mol Sci. 2025 Jun 30. pii: 6338. [Epub ahead of print]26(13):

The Whole Blood Transcriptomic Analysis in Sickle Cell Disease Reveals RUNX3 as a Potential Marker for Vaso-Occlusive Crises.

Safa Taha, Hawra Abdulwahab, Muna Aljishi, Ameera Sultan, Moiz Bakhiet, Salvatore Spicuglia, Mohamed Belhocine.

Sickle cell disease (SCD) is the most common hemoglobinopathy, caused by a mutation in the β-globin gene of hemoglobin. It predisposes patients to painful Vaso-occlusive crises (VOC) and multi-organ dysfunctions. The disease exhibits significant phenotypic variability, making it challenging to predict severity and outcomes. This study aimed to characterize the whole blood gene expression profile of Bahraini SCD patients, identifying differentially expressed genes during steady-state (n = 10) and VOC (n = 10) compared to healthy controls (n = 8). Analysis revealed 2073 and 3363 dysregulated genes during steady-state and VOC, respectively, compared to controls, with 1078 genes differentially expressed during VOC versus steady-state. Gene Ontology (GO) enrichment analysis highlighted significant deregulation in immune and hematopoietic pathways, including down-regulation of critical genes for immune modulation and hematopoietic balance. Notably, the transcription factor RUNX3, involved in immune cell differentiation and inflammation, was among the 668 down-regulated genes. RUNX3 was four-fold down-regulated in microarray analysis, three-fold in PCR, and showed a mean protein concentration of 11.13 pg/mL during VOC compared to 457.93 pg/mL during steady-state (p < 0.01). These findings suggest that RUNX3 may serve as a potential biomarker for VOC. Future large-scale validation, additional proteomic studies, and functional investigations are recommended to confirm its clinical utility and significance.

Keywords: SCD; VOC; biomarker; blood disease; hemolysis; inflammation; microarray; pain

DOI: https://doi.org/10.3390/ijms26136338

Sci Transl Med. 2025 Jul 16. 17(807): eadl4922

Complement is activated in patients with acute chest syndrome caused by sickle cell disease and represents a therapeutic target.

Despite being the first genetic disease described, sickle cell disease (SCD) continues to result in severe complications. Of these complications, acute chest syndrome (ACS), a form of acute lung injury, leads all-cause mortality. However, the pathophysiology of ACS remains incompletely understood, resulting in patients with ACS receiving only supportive measures. Here, we found that ACS is accompanied by activation of the complement pathway, an evolutionarily ancient innate immune system responsible for eliminating microbes. Using a well-defined preclinical model of SCD, hemolysis, a precursor of ACS, not only induced ACS but also drove robust complement activation. Artificial activation of complement alone similarly induced ACS, whereas genetic removal or pharmacological inhibition of complement rendered SCD mice resistant to ACS even after induction of hemolysis. These results demonstrate that complement drives ACS, establishing a link between SCD and this ancient form of immunity that provides an opportunity for targeted treatment of this complication.

DOI: https://doi.org/10.1126/scitranslmed.adl4922

Expert Rev Hematol. 2025 Jul 18. 1-10

Association between sickle cell disease and autoimmune diseases in Saudi population: a single center study.

Rehab Y Al-Ansari, Alexander Woodman, Hana Ibrahim Al Daajani, Mohammad Ibrahim Aljamily, Tawasoul Fadoul, Elham Hamid Alfallaj, Khaled Abdullah Hassan, Nada Rajab Al Zahrani, Zechariah Jebakumar Arulanantham, Mohammed Al Ghamdi.

BACKGROUND: The association between sickle cell disease (SCD) and autoimmune diseases (AID) is not well understood. This retrospective study aims to investigate the frequency of coexistence of AIDS with SCD.
RESEARCH DESIGN AND METHODS: This study was conducted in a tertiary care hospital. Data of n = 168 SCD patients between January 2016 and March 2023 were extracted and analyzed. Data included demographics, medications, hospitalization, phenotypes, presence of AIDs, and laboratory data.
RESULTS: The mean age of n = 168 SCD patients was 30.66 (SD ± 11.27), with 54.2% of cases being female. Overall, 88.56% of patients had HGBSS phenotyping. The incidence of SCD cases with negative AID was 84.52%, while incidence of SCD cases with positive AID was 15.47% (p = 0.00001). Systemic lupus erythematosus (SLE, 4.2%), hypothyroidism (3.6%), and antiphospholipid syndrome (APS, 3.6%) were the most common SCD-associated AIDs. In addition, 69.2% of AIDs-positive patients used hydroxyurea. A strong correlation was found between hospitalization rate and a positive AID (p = 0.03).
CONCLUSIONS: The result of this study represents the significant rate of AID and SCD coexistence. The findings require further study to substantiate the need to develop recommendations for screening and early detection of the SCD-associated AIDs.

Keywords: Sickle cell disease; autoimmune disease; connective tissue disease; cytokines; hydroxyurea

DOI: https://doi.org/10.1080/17474086.2025.2534713

Blood. 2025 Jul 17. 146(3): 268-270

Epigenetic drug remedies for SCD root cause pathophysiology.

Yogen Saunthararajah, Donald Lavelle.

DOI: https://doi.org/10.1182/blood.2025029447

Nat Rev Drug Discov. 2025 Jul 14.

CRISPR-based therapeutic genome editing for inherited blood disorders.

Sébastien Levesque, Daniel E Bauer.

Therapeutic genome editing promises to transform medicine. Pivotal discoveries have provided a diverse and versatile set of tools to correct pathogenic mutations or produce protective alleles using CRISPR-based technologies. These innovative therapies are especially adaptable for blood and immune disorders, where clinical methods allow haematopoietic stem cells (HSCs) to be mobilized, harvested, engineered ex vivo and transplanted back into a patient to permanently replace their blood system. This paradigm has been exemplified with the first US Food and Drug Administration (FDA)-approved CRISPR-Cas9 therapy for sickle cell disease and β-thalassaemia, exa-cel (Casgevy). Although promising, efficient delivery of gene edits involves complicated ex vivo manipulation and toxic myeloablative conditioning. The quiescent and elusive nature of HSCs also brings associated challenges. In this Review, we explore the state-of-the-art genome editing technologies of nucleases, base editors and prime editors, which hold promise to address unmet clinical needs for patients with inherited haematological disorders. We highlight the progress made for several disorders and discuss the challenges that remain for ex vivo and in vivo targeting of HSCs for next-generation gene therapies.

DOI: https://doi.org/10.1038/s41573-025-01236-y