In vivo brain delivery of BBB-enabled iduronate 2-sulfatase in rats.

Background: Iduronate-2-sulfatase (IDS) deficiency (MPS II; Hunter syndrome) is a disorder that exhibits peripheral and CNS pathology. The blood brain barrier (BBB) prevents systemic enzyme replacement therapy (ERT) from alleviating CNS pathology. We aimed to enable brain delivery of systemic ERT by using molecular BBB-Trojans targeting endothelial transcytosis receptors.

Conference Report from the European Bioanalysis Forum Workshop: toward harmonized implementation of the ICH M10 guideline.

In this report, the European Bioanalysis Forum shares the proposals for harmonized implementation of the ICH M10 guideline on bioanalytical method validation and study sample analysis from the ICH M10 workshop. The focus of the discussions was to understand new, changed or still ambiguous regulatory expectations in the guideline, as identified in feedback from the pre-workshop surveys or during the workshop. The proposals from the workshop aim at stimulating and helping a harmonized implementation of the guideline, and using our community as a sounding board during and after implementation to highlight areas of misalignment and to create a platform for continued sharing with the regulatory authorities in an effort to contribute to industry and regulators developing similar interpretations on guideline expectations.

A bacterial glycosidase enables mannose-6-phosphate modification and improved cellular uptake of yeast-produced recombinant human lysosomal enzymes.

Lysosomal storage diseases are treated with human lysosomal enzymes produced in mammalian cells. Such enzyme therapeutics contain relatively low levels of mannose-6-phosphate, which is required to target them to the lysosomes of patient cells. Here we describe a method for increasing mannose-6-phosphate modification of lysosomal enzymes produced in yeast.

Macrophage reprogramming by mycolic acid promotes a tolerogenic response in experimental asthma.

Rationale: Mycolic acid (MA) constitutes a major and distinguishing cell wall biolipid from Mycobacterium tuberculosis. MA interferes with the lipid homeostasis of alveolar macrophages, inducing differentiation into foamy macrophages exhibiting increased proinflammatory function.

Objectives: We verified the interference of this altered macrophage function with inhaled antigen-triggered allergic airway inflammation and underlying Th2 lymphocyte reactivity.