bims-sicedi 2025-09-14 papers

Front Pharmacol. 2025 ;16 1630994

Sickle cell disease: understanding pathophysiology, clinical features and advances in gene therapy approaches.

Muhammad Taher, Sofea 'Aisyah Aminondin, Nur Asyilah Nasir, Noor Afiqah Jasmadi, Nur Irdeena Nabella Nizam, Ilhan Syahmi Shahrul, Deny Susanti, Junaidi Khotib, Md Faiyazuddin, Riyanto Teguh Widodo, Muhammad Salahuddin Haris.

Sickle cell disease (SCD) is an inherited blood disorder marked by the production of abnormal hemoglobin, leading to the distortion-or sickling-of red blood cells. The SCD arises from a single-point mutation that substitutes glutamic acid with valine at the sixth codon of the β-globin chain in hemoglobin. This substitution promotes deoxyhemoglobin aggregation, elevating red blood cell stiffness, and triggering vaso-occlusive and hemolytic repercussions. To explore therapeutic advances in tackling this disease, this review analyzed articles published from January 2015 to January 2025 using the three databases using relevant keywords focusing on SCD and advancement in therapy. It was found that allogeneic hematopoietic stem cell (HSC) transplantation can alleviate symptoms but is limited by a shortage of well-matched donors and immunological challenges. In contrast, autologous gene-modified HSC transplantation via gene therapy offers comparable therapeutic benefits without associated immunological complications. Clinical trials utilizing lentiviral vector-mediated gene insertion have demonstrated promising therapeutic outcomes by preventing hemoglobin aggregation. Emerging gene editing approaches such as CRISPR/Cas9 are expanding treatment options, marking the transition of SCD gene therapy from theoretical concept to clinical application.

Keywords: CRISPR; anemia; gene editing; gene therapy; hematopoietic stem cell transplantation; hemoglobinopathies

DOI: https://doi.org/10.3389/fphar.2025.1630994

Blood Adv. 2025 Sep 23. 9(18): 4622-4623

A standardized metric to define a successful transition from pediatric to adult care in sickle cell disease.

Galia Pollock, Susanna Curtis.

DOI: https://doi.org/10.1182/bloodadvances.2025017088

Am J Respir Crit Care Med. 2025 Sep 12.

Cardiopulmonary Hemodynamic Determinants of Long-Term Survival in Sickle Cell Disease: Insights from the ETENDARD Study.

RATIONALE: Pulmonary hypertension (PH) is a serious cardiopulmonary complication of sickle cell disease (SCD), but the prognostic impact of hemodynamic parameters remains poorly defined.
OBJECTIVES: This study aimed to assess the clinical and long-term prognostic relevance of hemodynamic parameters in SCD.
METHODS: Data were analyzed from the French Etendard cohort. All 398 participants underwent echocardiography; those with tricuspid regurgitation velocity (TRV) ≥ 2.5 m/s proceeded to right heart catheterization. Over a minimum 10-year follow-up, we examined the clinical and prognostic significance of hemodynamic variables.
MEASUREMENTS AND MAIN RESULTS: PH defined by a mean pulmonary arterial pressure (mPAP) > 20 mmHg was identified in 44 patients (11%). Among them, 26 (6.5%) had a pulmonary arterial wedge pressure (PAWP) ≤ 5 mmHg, and 18 (4.5%) had a PAWP>15 mmHg. Mortality during follow-up was 11.1%. A significant association was found between pulmonary vascular resistance (PVR) levels and mortality risk, with a threshold identified at 1.5 Wood units through ROC analyses. In patients with mPAP > 20 mmHg and PVR ≥ 1.5 WU, the adjusted hazard ratio (HR) for mortality was 4.27 (95% CI: 1.88-9.74; p < 0.001). A hemolytic phenotype and the presence of systemic complications, including hypertension, left ventricular diastolic dysfunction, renal impairment, and leg ulcers, were associated with elevated PVR and increased mortality risk.
CONCLUSION: A PVR threshold of 1.5 WU emerges as a key predictor of mortality in patients with a mPAP above 20 mmHg, particularly when assessed in conjunction with markers of hemolysis and systemic complications.

Keywords: pulmonary hypertension; pulmonary vascular resistance; sickle cell disease; survival

DOI: https://doi.org/10.1164/rccm.202502-0353OC

Bone Marrow Transplant. 2025 Sep 12.

Early administration of selected CD34 peripheral blood stem cell following bone marrow transplantation to prevent graft rejection: experience in haploidentical transplant for sickle cell disease.

Clara Barthélemy, Matthieu Jestin, Anne Brignier, Nathalie Parquet, Florian Chevillon, Nicolas Boissel, Justine Nasone, Régis Peffault de Latour, Lionnel Faivre, Nathalie Dhédin.

DOI: https://doi.org/10.1038/s41409-025-02685-0

JAMA Pediatr. 2025 Sep 08.

Mortality Rate Trends for Sickle Cell Disease and Cystic Fibrosis in the US.

Hiluf Ebuy Abraha, Marie Thoma, Nansi S Boghossian.

DOI: https://doi.org/10.1001/jamapediatrics.2025.2997

PLoS One. 2025 ;20(9): e0332069

Healthcare providers' knowledge on sickle cell disease and its management: A pre- and post-training test evaluation outcome.

Vivian Paintsil, Evans Xorse Amuzu, Eunice Ahmed, Yaa Gyamfua Oppong-Mensah, Lesley Osei, Bernice Eklu, Suraj Yawnumah Abubakar, Lawrence Osei-Tutu, Daniel Ansong, Alex Osei-Akoto, Fred Stephen Sarfo.

In resource-limited settings in Africa, which harbour the greatest burden of Sickle Cell Disease (SCD) globally, poor care outcomes are driven in part, by a lack of trained healthcare providers (HCP) and an absence of context-specific treatment guidelines appropriate to the level of healthcare facility. The study aimed to evaluate the impact of a structured training program on HCP's knowledge of SCD in Ghana. This was prospective cross-sectional study involving HCPs from 46 health facilities from 4 out of 16 regions in Ghana. A curriculum and standard slides were developed by SCD experts based on the Sickle Pan African Research Consortium (SPARCO)Standards of care for Sickle Cell Disease in sub-Saharan Africa clinical recommendations. A full-day workshop highlighting the general overview of SCD, diagnosis, health maintenance, acute and chronic complications was then organized. A pre-training test and a post-training test immediately after the workshop were administered and analyzed. A total of 543 HCPs were trained, mostly from primary level facilities (77.7%). The average number of years working with SCD patients was 5 years (Range: < 1-20 years). Most (93%) HCPs had experience with SCD patients but only 43% reported using a form of guideline for the care of SCD patients. The average score in the pre-training test was 8.4/20 (SD:3.3) increasing to 13.1/20(SD:3.6) in the post-training test, (p-value <0.01). The average proportion of persons indicating a correct answer for a question was 50% at the pre-training test increasing to approximately 69% in the post-test, (p-value <0.01). The knowledge of HCPs about SCD and its management was generally low but improved significantly after the standardized training. Further studies are required to assess the impact of HCP training on health outcomes of SCD in resource limited settings.

DOI: https://doi.org/10.1371/journal.pone.0332069