Global seroprevalence of neutralizing antibodies against adeno-associated virus serotypes used for human gene therapies.

Adeno-associated virus (AAV) vectors are promising gene therapy candidates, but pre-existing anti-AAV neutralizing antibodies (NAbs) pose a significant challenge to successful gene delivery. Knowledge of NAb seroprevalence remains limited and inconsistent. We measured activity of NAbs against six clinically relevant AAV serotypes across 10 countries in adults ( = 502) and children ( = 50) using a highly sensitive transduction inhibition assay.

Understanding AAV vector immunogenicity: from particle to patient.

Gene therapy holds promise for patients with inherited monogenic disorders, cancer, and rare genetic diseases. Naturally occurring adeno-associated virus (AAV) offers a well-suited vehicle for clinical gene transfer due to its lack of significant clinical pathogenicity and amenability to be engineered to deliver therapeutic transgenes in a variety of cell types for long-term sustained expression. AAV has been bioengineered to produce recombinant AAV (rAAV) vectors for many gene therapies that are approved or in late-stage development.

Binding and neutralizing anti-AAV antibodies: Detection and implications for rAAV-mediated gene therapy.

Assessment of anti-adeno-associated virus (AAV) antibodies in patients prior to systemic gene therapy administration is an important consideration regarding efficacy and safety of the therapy. Approximately 30%-60% of individuals have pre-existing anti-AAV antibodies. Seroprevalence is impacted by multiple factors, including geography, age, capsid serotype, and assay type.

How to assess, detect, and manage joint involvement in the era of transformational therapies: Role of point-of-care ultrasound.

Background: Patients with haemophilia experience recurring hemarthroses, mainly involving knees, elbows and ankles, which lead to haemophilic arthropathy, the major chronic complication of haemophilia. With new approaches to haemophilia treatment leading to fewer joint bleeds and, in some cases, no bleeding events, assessing whether current outcome assessment tools provide adequate sensitivity and specificity for management and care of patients with haemophilia is needed.

Methods: An overview of current imaging tools for monitoring joint health, novel osteochondral damage and synovial proliferation biomarkers, and the relationship between assessments for functionality and imaging modalities is provided.

Examining patient and professional perspectives in the UK for gene therapy in haemophilia.

Introduction: With the development of gene therapy for people with haemophilia (PWH), it is important to understand how people impacted by haemophilia (PIH) and clinicians prioritise haemophilia treatment attributes to support informed treatment decisions.

Objective: To examine the treatment attribute preferences of PIH and clinical experts in the United Kingdom (UK) and to develop a profile of gene therapy characteristics fit for use in future discrete choice experiments (DCEs).

Methods: Semi-structured interviews were conducted with PIH (n = 14) and clinical experts (n = 6) who ranked pre-defined treatment attributes by importance.

Estimating the Prevalence of Transthyretin Amyloid Cardiomyopathy in a Large In-Hospital Database in Japan.

Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM)-a debilitating, fatal disease resulting from the deposition of transthyretin (TTR) amyloid fibrils-can be hereditary due to mutations in the TTR gene (ATTRm) or wild type (ATTRwt). The global prevalence of ATTR-CM is largely unknown, although likely underestimated, with no formal epidemiological prevalence studies in Japan. This study aimed to estimate the prevalence of ATTR-CM in a large in-hospital database in Japan.

Cell damage following carbon monoxide releasing molecule exposure: implications for therapeutic applications.

The cytoprotective properties of carbon monoxide (CO) gas and CO-releasing molecules (CORMs) are well established. Despite promising pre-clinical results, little attention has been paid to the toxicological profile of CORMs. The effects of CORM-2 and its CO-depleted molecule (iCORM-2) (20-400 μM) were compared in primary rat cardiomyocytes and two cell lines [human embryonic kidney (HeK) and Madine-Darby canine kidney Cells (MDCK)].

Tin protoporphyrin provides protection following cerebral hypoxia-ischemia: involvement of alternative pathways.

The contribution of heme oxygenase (HO)-linked pathways to neurodegeneration following cerebral hypoxia-ischemia (HI) remains unclear. We investigated whether HO modulators affected HI-induced brain damage and explored potential mechanisms involved. HI was induced in 26-day-old male Wistar rats by left common carotid artery ligation, followed by exposure to a humidified atmosphere of 8% oxygen for 1 hr.

Domoic acid impairment of cardiac energetics.

Excitatory mediated neuronal injury has been shown to involve a complex cascade of events. However, the associated cardiac damage reported in humans and marine animals following exposure to excitotoxins has not been well characterized. We hypothesized that the excitotoxin domoic acid can traverse cardiac cell membranes and elicit a deleterious effect on cardiac mitochondrial energetics.

Expanding retrograde saphenous vein graft aneurysm treated with endovascular coiling.

Saphenous vein graft aneurysm is a potentially fatal complication of coronary artery bypass grafting and usually requires surgery. This report describes endovascular coiling of a saphenous vein graft aneurysm that developed after redo coronary artery bypass grafting. The aneurysm occurred in a proximally occluded saphenous vein graft after revascularization of the same target vessel.