Development of tailored splice-switching oligonucleotides for progressive brain disorders in Europe: development, regulation, and implementation considerations.

Splice-modulating antisense oligonucleotides (ASOs) offer treatment options for rare neurological diseases, including those with very rare mutations, where patient-specific, individualized ASOs have to be developed. Inspired by the development of milasen, the 1 Mutation 1 Medicine (1M1M) and Dutch Center for RNA Therapeutics (DCRT) aim to develop patient-specific ASOs and treat eligible patients within Europe and the Netherlands, respectively. Treatment will be provided under a named patient setting.

Improving Translation by Identifying Evidence for More Human-Relevant Preclinical Strategies.

Preclinical animal studies are performed to analyse the safety and efficacy of new treatments, with the aim to protect humans. However, there are questions and concerns about the quality and usefulness of preclinical animal research. Translational success rates vary between 0 and 100%, and no clear relationship has been found with possible predictive factors such as animal species or field of research.

A Systematic Review Comparing Experimental Design of Animal and Human Methotrexate Efficacy Studies for Rheumatoid Arthritis: Lessons for the Translational Value of Animal Studies.

Increased awareness and understanding of current practices in translational research is required for informed decision making in drug development. This paper describes a systematic review of methotrexate for rheumatoid arthritis, comparing trial design between 147 animal and 512 human studies. Animal studies generally included fewer subjects than human studies, and less frequently reported randomisation and blinding.

Assessing the application of the 3Rs: a survey among animal welfare officers in The Netherlands.

Implementation of the 3Rs (Replacement, Refinement and Reduction) in animal studies is a legal requirement in many countries. In The Netherlands, animal welfare officers (AWOs) are appointed to monitor the welfare of laboratory animals. As part of this task, AWOs give advice to researchers and can therefore have an influential role in implementing 3R methods in research.