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Loss of pulmonary function is a main cause of early morbidity and mortality in patients with Duchenne muscular dystrophy (DMD). Standard of care guidelines recommend regular assessment of pulmonary function by hospital-based spirometry to detect onset and monitor progression of pulmonary function decline. To assess the feasibility of home-based monitoring of pulmonary function by a hand-held device (HHD) in adolescent and adult patients with DMD over a period of 12 months. In the phase III randomized placebo-controlled DELOS trial in 10–18 year old DMD patients, peak expiratory flow (PEF) measurements were collected weekly at home by the patient (assisted by parent/caregiver) using a peak flow meter HHD. Adherence to the use of the HHD was assessed and 12-month changes in PEF as percent of predicted (PEF% p) for the idebenone (N = 31) and the placebo treatment groups (N = 33) from HHD-derived data were compared to results from hospital-based spirometry. A total of 2689 individual HHD assessments were analysed. Overall adherence to the use of the HHD over the course of the 12-month study duration was good (75.9%, SD 21.5%) and PEF% p data obtained at the same day by HHD and standard spirometry correlated well (Spearman’s rho 0.80; p < 0.001). Several analysis methods of HHD-derived data for PEF% p consistently demonstrate that idebenone treatment slowed the decline in PEF% p compared to placebo, which supports the statistically significant difference in favour of idebenone for PEF% p measured by standard spirometry. This study demonstrates that home-based monitoring of pulmonary function in adolescent patients with DMD using a HHD is feasible, provides reliable data compared to hospital-based spirometry and is therefore suitable for use in clinical practice and for clinical trials.

Patients with DMD experience progressive restrictive respiratory disease and eventual respiratory failure. Standard of care guidelines command changes in disease management when forced vital capacity percent of predicted (FVC% p) falls below clinically relevant thresholds. The Phase 3 DELOS trial in patients with DMD demonstrated that idebenone reduces the loss of peak expiratory flow and FVC compared to placebo (Buyse GM, et al.; Lancet 2015; 385 : 1748-57). Post-hocanalyses were conducted to assess whether treatment with idebenone could reduce the risk of patients dropping below clinically meaningful thresholds of FVC% p. The DELOS trial enrolled DMD patients 10–18 years of age not using glucocorticoids to receive idebenone (N = 31) or placebo (N = 33) for 12 months. Change from baseline in FVC and FVC% p was assessed by hospital spirometry and analyzed by mixed model of repeated measures and slope analysis and proportions of patients falling below clinically meaningful thresholds of FVC% p were compared. The change over 1 year in FVC and FVC% p showed a consistent pattern in favor of idebenone treatment across multiple analysis methods and fewer patients in the idebenone group declined by a margin of 10% or more in FVC and FVC% p compared to placebo. There were also fewer patients in the idebenone group (15%) with a decline below FVC% p of 50% compared to the placebo group (25%) and fewer patients in the idebenone group (28%) showed a decline below FVC% p of 50% or 40% or 30% compared to the placebo group (43%). These data added to the consistency and clinical meaningfulness of findings from the DELOS trial showing that idebenone can slow the loss of pulmonary function in patients with DMD.

Cardiorespiratory failure is the leading cause of death in Duchenne muscular dystrophy. Based on preclinical and phase 2 evidence, we assessed the efficacy and safety of idebenone in young patients with Duchenne muscular dystrophy who were not taking concomitant glucocorticoids.

The authors investigated the correlation of protan and tritan color vision with disease characteristics in Leber hereditary optic neuropathy (LHON). The authors also characterized the therapeutic potential of idebenone in protecting patients from developing dyschromatopsia in LHON.

The atroposelective ring opening of lactone-bridged biaryl systems is the key step in the total synthesis of a series of axially chiral biaryl natural products and useful reagents or catalysts for asymmetric synthesis. For a more in-depth understanding of the mechanism and stereochemical course of this remarkable cleavage reaction, a seven-membered ether analog of such useful biaryl lactones has been investigated structurally, both experimentally, by X-ray diffraction analysis, and by ab initio calculations (B3LYP/6-31G*). In a nearly perfect agreement, both methods show that these seven-membered bridged biaryls do not constitute helicene-like distorted molecules, but ‘true’ biaryls, whose sufficiently long lactone or ether bridge allows the two aromatic systems to adopt a large dihedral angle to each other, without any noticeable deviation from planarity for the two aromatic systems - in contrast to related six-membered analogs, which can rather be considered as helicene-like twisted polycyclic systems.

3D QSAR models based on the CoMSIA descriptor fields were established using a diverse data set of 53 antimalarial biaryl compounds (tested in vitro against a chloroquine-resistant strain of Plasmodium falciparum), consisting mainly of naphthylisoquinoline alkaloids, but also including phenylanthraquinone structures and naphthylindenes. For the alignment, two commercially available automated approaches, FLEXS and GASP, were compared; initially none of them succeeded in treating the important phenomenon of axial chirality correctly, but after some manual refinement of the alignments initially obtained, the best overall model, based on a modified FLEXS alignment, showed a q2(cross-validated r2) of 0.818 (eight components), using only the hydrophobic and the H-bond donor and acceptor fields. Using a test set of five compounds the model showed a squared multiple correlation coefficient for the test set (predictive r2) of 0.578. The analysis of the 3D contour maps permitted interesting conclusions about the effects of particular functional groups on the biological activity and will now guide the design of novel, hopefully even more active compounds.

Simple peroxomolybdenum Mimoun complexesbecome catalytically active in phase‐transfer epoxidations with hydrogen peroxide, if the active oxenoid is extracted from the water into the organic phase by surfactant‐type ligands OER3(E = N, P, As; R = long‐chain alkyl; see scheme). Mechanistic studies, Raman spectroscopy, and denisty functional calculations are combined in an investigation of the active species.

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