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Thrombotic Microangiopathy Associated with Systemic Adeno-Associated Virus Gene Transfer: Review of Reported Cases.
Hum Gene Ther
January 2025
BridgeBio Gene Therapy, Palo Alto, California, USA.
Complement-mediated thrombotic microangiopathy (TMA) in the form of atypical hemolytic uremic syndrome (aHUS) has emerged as an immune complication of systemic adeno-associated virus (AAV) gene transfer that was unforeseen based on nonclinical studies. Understanding this phenomenon in the clinical setting has been limited by incomplete data and a lack of uniform diagnostic and reporting criteria. While apparently rare based on available information, AAV-associated TMA/aHUS can pose a substantial risk to patients including one published fatality.
View Article and Find Full Text PDFTowards a Platform Chromatography Purification Process for Adeno-Associated Virus (AAV).
Biotechnol J
January 2025
School of Chemical and Bioprocess Engineering, University College Dublin, Dublin, Ireland.
Adeno-associated virus (AAV) is a versatile viral vector technology that can be engineered for specific functionality in vaccine and gene therapy applications. One of the major challenges in AAV production is the need for a GMP-ready platform-based approach to downstream processing, as this would lead to a standardized method for multiple products. Chromatography has huge potential in AAV purification, as it is a scalable method that would enable manufacturing to a high degree of purity, potency, and consistency.
View Article and Find Full Text PDFPatient perspective: Is intensive screening of women at high risk of breast cancer evidence-based medicine or ?
Womens Health (Lond)
January 2025
Department of Pharmacy Practice, Midwestern University College of Pharmacy, Glendale Campus, Glendale, AZ, USA.
In 2023, a breast cancer risk assessment and a subsequent positive test for the BRCA-2 genetic mutation brought me to the uncomfortable intersection of a longstanding career as an advocate for high-quality medical evidence to support shared patient-provider decision making and a new role as a high-risk patient. My search for studies of available risk-management options revealed that the most commonly recommended approach for women with a ⩾20% lifetime breast cancer risk, intensive screening including annual mammography and/or magnetic resonance imaging beginning at age 25-40 years, was supported only by cancer-detection statistics, with almost no evidence on patient-centered outcomes-mortality, physical and psychological morbidity, or quality of life-compared with standard screening or a surgical alternative, bilateral risk-reducing mastectomy. In this commentary, I explore parallels between the use of the intensive screening protocol and another longstanding women's health recommendation based on limited evidence, the use of hormone therapy (HT) for postmenopausal chronic disease prevention, which was sharply curtailed after the publication of the groundbreaking Women's Health Initiative trial in 2002.
View Article and Find Full Text PDFAntagonisation of Prokineticin Receptor-2 Attenuates Preeclampsia Symptoms.
J Cell Mol Med
January 2025
Interdisciplinary Research Institute of Grenoble, IRIG-Biosanté, University Grenoble Alpes, INSERM, CEA, UMR 1292, Grenoble, France.
Preeclampsia (PE) is the most threatening pathology of human pregnancy. Placenta from PE patients releases harmful factors that contribute to the exacerbation of the disease. Among these factors is the prokineticin1 (PROK1) and its receptor, PROKR2 that we identified as a mediators of PE.
View Article and Find Full Text PDFTinagl1 restores tamoxifen sensitivity and blocks fibronectin-induced EMT by simultaneously blocking the EGFR and β1-integrin/FAK signaling pathways in tamoxifen-resistant breast cancer cells.
IUBMB Life
January 2025
Department of General Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Tamoxifen (TAM) is employed to treat premenopausal ER-positive breast cancer patients, but TAM resistance is the main reason affecting its efficacy. Thus, addressing TAM resistance is crucial for improving therapeutic outcomes. This study explored the potential role of Tinagl1, a secreted extracellular matrix protein, whose expression is compromised in TAM-resistant MCF-7 breast cancer cells (MCF-7R).
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