Specific analysis of SOD1 enzymatic activity in CSF from ALS patients with and without SOD1 mutations.

Mutations in superoxide dismutase-1 (SOD1) are a cause of hereditary amyotrophic lateral sclerosis (ALS) through a gain-of-function mechanism involving unfolded mutant SOD1. Intrathecal gene therapy using the antisense-oligo-nucleotide drug tofersen to reduce SOD1 expression delays disease progression and has recently been approved in the United States and the European Union. However, the discovery of children homozygous for inactivating SOD1 mutations developing the SOD1 Deficiency Syndrome (ISODDES) with injury to the motor system suggests that a too low SOD1 antioxidant activity may be deleterious in humans.

Analysis of proteome-wide degradation dynamics in ALS SOD1 iPSC-derived patient neurons reveals disrupted VCP homeostasis.

Mutations in SOD1 cause amyotrophic lateral sclerosis (ALS) through gain-of-function effects, yet the mechanisms by which misfolded mutant SOD1 (mutSOD1) protein impairs human motor neurons (MNs) remain unclear. Here, we use induced-pluripotent-stem-cell-derived MNs coupled to metabolic stable isotope labeling and mass spectrometry to investigate proteome-wide degradation dynamics. We find several proteins, including the ALS-causal valosin-containing protein (VCP), which predominantly acts in proteasome degradation and autophagy, that degrade slower in mutSOD1 relative to isogenic control MNs.

Reference equations for quadriceps strength, endurance and power: a multicentre study.

Introduction: The lack of reference values of lower-limb muscle function hinders the clinical recommendations of its measurement in patients with COPD. Therefore, this study aimed to develop reference equations to predict reference values for quadriceps strength, endurance and power and evaluate their construct validity in patients with COPD.

Methods: Quadriceps strength, endurance and power were assessed in 158 healthy individuals and 87 patients with COPD.

Experiences of Using an Electronic Health Tool Among Health Care Professionals Involved in Chronic Obstructive Pulmonary Disease Management: Qualitative Analysis.

Background: Chronic obstructive pulmonary disease (COPD) is one of the most common and deadliest chronic diseases of the 21st century. eHealth tools are seen as a promising way of supporting health care professionals in providing evidence-based COPD care, for example, by reinforcing information and interventions provided to the patients and providing easier access and support to the health care professional themselves. Still, knowledge is scarce on the experience of using eHealth tools from the perspective of the health care professional involved in COPD management.