Long-term safety and efficacy of Oleogel-S10 (birch bark extract) in epidermolysis bullosa: 24-month results from the Phase III EASE Study.

Background: Epidermolysis bullosa (EB) is a group of rare, severe, genetic disorders characterised by persistent skin fragility and open wounds. EB manifests as cutaneous and mucosal blistering, erosions and impaired wound healing.

Objectives: To determine the long-term efficacy, tolerability and safety of Oleogel-S10 (birch bark extract) in dystrophic (DEB) and junctional (JEB) EB in the 24-months open-label phase (OLP) of the EASE study.

Probing mechanical selection in diverse eukaryotic genomes through accurate prediction of 3D DNA mechanics.

Connections between the mechanical properties of DNA and biological functions have been speculative due to the lack of methods to measure or predict DNA mechanics at scale. Recently, a proxy for DNA mechanics, cyclizability, was measured by loop-seq and enabled genome-scale investigation of DNA mechanics. Here, we use this dataset to build a computational model predicting bias-corrected intrinsic cyclizability, with near-perfect accuracy, solely based on DNA sequence.

DNA aptamers that modulate biological activity of model neurons.

There is an urgent need for agents that promote health and regeneration of cells and tissues, specifically to treat diseases of the aging nervous system. Age-associated nervous system degeneration and various diseases are driven by many different biochemical stresses, often making it difficult to target any one disease cause. Our laboratory has previously identified DNA aptamers with apparent regenerative properties in murine models of multiple sclerosis by selecting aptamers that bind oligodendrocyte membrane preparations.

Conformation-specific RNA aptamers for phenotypic distinction between normal von Willebrand factor and type 2B von Willebrand disease.

The A1 domain in Von Willebrand Factor (VWF) initiates coagulation through binding to platelet glycoprotein GPIbα receptors. Von Willebrand Disease (VWD)-Mutations in A1 that either impair (type 2M) or enhance (type 2B) platelet adhesion to VWF can locally destabilize and even misfold the domain. We leveraged misfolding in the gain-of-function type 2B VWD phenotype as a target, distinct from the normal conformation.

Similar deficiencies, different outcomes: succinate dehydrogenase loss in adrenal medulla vs. fibroblast cell culture models of paraganglioma.

Heterozygosity for loss-of-function alleles of the genes encoding the four subunits of succinate dehydrogenase (SDHA, SDHB, SDHC, SDHD), as well as the SDHAF2 assembly factor predispose affected individuals to pheochromocytoma and paraganglioma (PPGL), two rare neuroendocrine tumors that arise from neural crest-derived paraganglia. Tumorigenesis results from loss of the remaining functional SDHx gene copy, leading to a cell with no functional SDH and a defective tricarboxylic acid (TCA) cycle. It is believed that the subsequent accumulation of succinate competitively inhibits multiple dioxygenase enzymes that normally suppress hypoxic signaling and demethylate histones and DNA, ultimately leading to increased expression of genes involved in angiogenesis and cell proliferation.