In the healthcare system, lower leg fractures remain relevant, incurring costs related to surgical treatment, hospitalization, and rehabilitation. The duration of treatment may vary depending on the individual case and its severity. Casting as a post-surgical fracture treatment is a common method in human and experimental veterinary medicine. Despite the high importance of sheep in preclinical testing materials for osteosynthesis, there is no standardised cast system ensuring proper stabilisation and functionality of hind limbs during the healing of tibia fractures or defects. Existing treatment approaches for tibial osteosynthesis in laboratory animal science include sling hanging, external fixators, or former Achilles tendon incision. These methods restrict animal movement for 4–6 weeks, limit species-typical behaviour, and impact social interactions. Our pilot study introduces a Standardised Walking Cast (SWC) for sheep, enabling immediate physiological movement post surgery. Seven Rhone sheep (female, 63.5 kg ± 6.45 kg) each with a single tibia defect (6 mm mechanical drilled defect) underwent SWC application for 4 weeks after plate osteosynthesis. The animals bore weight on their operated leg from day one, exhibiting slight lameness (grade 1–2 out of 5). Individual step lengths showed good uniformity (average deviation: 0.89 cm). Group housing successfully started on day three after surgery. Weekly X-rays and cast changes ensured proper placement, depicting the healing process. This study demonstrates the feasibility of using an SWC for up to 72 kg of body weight without sling hanging via ceiling mounting or external fixation techniques. Allowing species-typical movement and social behaviour can significantly improve the physiological behaviour of sheep in experiments, contributing to refinement.

The lysosomal storage disorder Fabry disease results from α‐galactosidase A deficiency, leading to excessive glycosphingolipid substrate accumulation, primarily globotriaosylceramide (Gb3). While the underlying molecular mechanisms remain elusive, multi‐systemic complications ultimately culminate in premature death, with heart failure being the leading cause of death. Current treatment options fail to treat Fabry disease adequately and only delay its progression. Preclinical studies on an alternative approach, systemic delivery of nucleoside‐modified GLA mRNA (modGLA), suggest improved effectiveness over existing therapies in reducing glycosphingolipid levels in the heart. It remains unclear whether modGLA can rescue Fabry cardiomyopathy phenotypes at the cellular level, which are not faithfully recapitulated in current animal models. To address this, we investigated characteristic phenotypes in two new models of Fabry cardiomyopathy utilizing human iPSC‐derived cardiomyocytes in transcriptomic and functional analyses. These human Fabry disease cardiomyocytes displayed broad transcriptional dysregulation, apoptosis, mitochondrial dysfunction, impaired reactive oxygen species handling, altered contractility, and enhanced calcium transient decay parameters. Mechanistically, phospholamban hyperphosphorylation may contribute to this calcium dysregulation. Consistently, modGLA therapy restored α‐galactosidase A activity, reduced glycosphingolipid deposition, and normalized molecular alterations, including phospholamban hyperphosphorylation and calcium decay parameters, supporting modGLA as a promising therapeutic strategy for Fabry disease.

Preregistration of animal studies is increasingly promoted as a methodological Refinement that can reduce bias, prevent unnecessary duplication and ultimately benefit animal welfare. Despite dedicated open registries (i.e., the Animal Study Registry of the German Centre for the Protection of Laboratory Animals (ASR) and preclinicaltrials.eu (PCT)), uptake remains low. The perceived time burden and limited awareness are the most frequently mentioned barriers, although these registries have been available since 2018 and 2019. In this feasibility study, eleven researchers (Beginners n = 3, Trainees n = 3, Experts n = 5) preregistered two preclinical protocols (rat and pig) on each platform, while completion time, mouse clicks, cursor distance, and scroll events were registered. An anonymous survey collected free-text comments. Completion time was substantially longer on ASR than on PCT for both the rat protocol (99.5 ± 29.1 vs. 39.5 ± 4.9 min) and the pig protocol (53.1 ± 17.2 vs. 25.8 ± 8.5 min), with the same direction for the other parameters. All eleven participants preferred PCT, and completion time decreased with practice. Preregistration is technically feasible on either platform. However, structured training and targeted usability improvements could reduce the activation cost and support its role as a Refinement strategy in laboratory animal science.