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Background: Due to improved treatment options, more SMA patients reach childbearing age. Currently, limited data on pregnant SMA patients is available, especially in relation to disease-modifying therapies (DMT). This case report helps to elucidate new approaches for future guidelines in the management of pregnancy and SMA., Case Report: A 33-year-old wheelchair-bound patient with SMA type 3 (sitter) became pregnant following 36 months of Nusinersen treatment. The last dose was administered in the third gestational week. After pregnancy was confirmed, therapy was stopped immediately. A healthy child was born in the 34th gestational week by caesarean section. After a short nursing period, Nusinersen was restarted 6 weeks after the expected gestational date. At this time, the patient reported deteriorated motor functions, which stabilized at a lower level compared to pre-pregnancy in the 2-year follow-up, despite restarting Nusinersen treatment., Discussion: So far, only few cases of successful pregnancies of SMA patients on DMT have been reported. In natural history, the majority of patients experienced an increased deterioration of motor function while fetal outcome was not impaired. Our case shows that although Nusinersen treatment was applied in the third gestational week prior to proof of pregnancy, outcome was positive for mother and child. Future studies will have to determine whether ongoing treatment with Nusinersen during pregnancy should be recommended., Competing Interests: Declarations. Ethics approval and consent to participate: The patient has consented to participate in the publishing of her case. Ethics approval was not necessary. Consent for publication: The patient has given written informed consent to the publication of her case including personal and clinical details and possible images. Competing interests: Miriam Hiebeler received Speaker Honoraria from Biogen. Maggie C. Walter has served on advisory boards for Avexis, Biogen, Novartis, Pfizer, Roche, Santhera, Sarepta, Pharnext, PTC Therapeutics, Ultragenyx, Wave Sciences, received funding for Travel or Speaker Honoraria from Avexis, Biogen, PTC Therapeutics, Ultragenyx, Santhera, Sarepta, and worked as an ad-hoc consultant for AskBio, Audentes Therapeutics, Avexis, Biogen Pharma GmbH, Fulcrum Therapeutics, GLG Consult, Guidepoint Global, Gruenenthal Pharma, Novartis, Pharnext, PTC Therapeutics, Roche. Simone Thiele has no conflicts to report., (© 2024. The Author(s).)

The plastic waste crisis is among humanity's most urgent challenges. However, widespread adoption of sustainable plastics is hindered by their often inadequate processing characteristics and performance. Here, we introduce a bio-inspired strategy for the modification of a representative high molar mass, biodegradable aliphatic polyester that helps overcome these limitations and remains effective at molar masses far greater than the entanglement molar mass. We use co-assembly of oligopeptide-based polymer end groups and a low molar mass additive to create a hierarchical structure characterized by regularly spaced nanofibrils interconnected by entangled polymer segments. The modified materials show a rubbery plateau at temperatures above their melting point, associated with strongly increased melt strength, extraordinary melt extensibility, improved dimensional stability, and accelerated crystallization. These thermomechanical property changes open up otherwise inaccessible processing routes and offer considerable scope for improving solid-state properties, thereby addressing typical shortcomings of sustainable alternatives to conventional plastics., Competing Interests: Competing interests: While working on this project, S.H. was employed by Mitsubishi Chemical Corporation, which also partly funded the research project. Additionally, H.F., D.G., C.J.G.P., O.O., and S.H. are inventors on the two related patent applications WO2020229594 and WO2019096365., (© 2024. The Author(s).)

Purpose: To quantify outer retina structural changes and define novel biomarkers of inherited retinal degeneration associated with biallelic mutations in RPE65 (RPE65-IRD) in patients before and after subretinal gene augmentation therapy with voretigene neparvovec (Luxturna)., Methods: Application of advanced deep learning for automated retinal layer segmentation, specifically tailored for RPE65-IRD. Quantification of five novel biomarkers for the ellipsoid zone (EZ): thickness, granularity, reflectivity, and intensity. Estimation of the EZarea in single and volume scans was performed with optimized segmentation boundaries. The control group was age similar and without significant refractive error. Spherical equivalent refraction and ocular length were evaluated in all patients., Results: We observed significant differences in the structural analysis of EZ biomarkers in 22 patients with RPE65-IRD compared with 94 healthy controls. Relative EZ intensities were already reduced in pediatric eyes. Reductions of EZ local granularity and EZ thickness were only significant in adult eyes. Distances of the outer plexiform layer, external limiting membrane, and Bruch's membrane to EZ were reduced at all ages. EZ diameter and area were better preserved in pediatric eyes undergoing therapy with voretigene neparvovec and in patients with a milder phenotype., Conclusions: Automated quantitative analysis of biomarkers within EZ visualizes distinct structural differences in the outer retina of patients including treatment-related effects. The automated approach using deep learning strategies allows big data analysis for distinct forms of inherited retinal degeneration. Limitations include a small dataset and potential effects on OCT scans from myopia at least -5 diopters, the latter considered nonsignificant for outer retinal layers.