Immunologic investigations into transgene directed immune-mediated myositis following delandistrogene moxeparvovec gene therapy.

Delandistrogene moxeparvovec is an rAAVrh74 vector-based gene transfer therapy that delivers a transgene encoding delandistrogene moxeparvovec micro-dystrophin, an engineered, functional form of dystrophin shown to stabilize or slow disease progression in DMD. It is approved in the US and in other select countries. Two serious adverse event cases of immune-mediated myositis (IMM) were reported in the phase Ib ENDEAVOR trial (NCT04626674).

Deleterious impacts of Western diet on jejunum function and health are reversible.

The goal of this study was to determine whether the influence of a high-fat high-sugar diet (Western diet) on intestinal function and health was reversible. We measured transepithelial short circuit current (), across freshly isolated segments of jejunum from male C57Bl/6J mice randomly assigned to one of the following groups for the study duration: high-fat high-sugar diet for 24 wk (HFHS), HFHS diet for 12 wk then switched to standard chow and water for a further 12 wk (Std), and lean controls (standard chow and water for 24 wk). At the completion of the study, segments of jejunum were frozen for Western blot determination of key proteins involved in secretory and absorptive functions, as well as senescence.

Repurposed Medicines: A Scan of the Non-commercial Clinical Research Landscape.

Medicine repurposing is a strategy to identify new uses for the existing medicines for the purpose of addressing areas of unmet medical need. This paper aims to provide horizon scanning intelligence on repurposed medicines that are evaluated by non-commercial organizations such as academia and highlights opportunities for further research to improve patient health outcomes. A scan of the clinical landscape of non-commercially sponsored repurposed medicines is routinely conducted by the NIHR Innovation Observatory (IO).

Genetic Manipulation of Caveolin-1 in a Transgenic Mouse Model of Aortic Root Aneurysm: Sex-Dependent Effects on Endothelial and Smooth Muscle Function.

Marfan syndrome (MFS) is a systemic connective tissue disorder stemming from mutations in the gene encoding Fibrillin-1 (Fbn1), a key extracellular matrix glycoprotein. This condition manifests with various clinical features, the most critical of which is the formation of aortic root aneurysms. Reduced nitric oxide (NO) production due to diminished endothelial nitric oxide synthase (eNOS) activity has been linked to MFS aortic aneurysm pathology.