Standards in preclinical efficacy studies
The development of new drugs designed specifically for neuromuscular diseases and the application of drugs originally approved for a different disease almost always involves the need for the drug in question to be tested in animals that have been developed to model the human disease as closely as possible. Usually it is only if the drug appears to have an effect on the animal model that it is considered worth taking it forward into clinical trial in humans. Such studies in the preclinical phase are key to assessing the efficacy of the drug and predicting success in humans with the disease.
Because the preclinical phase of research is so critical to the decisions made about a possible future therapy, it is very important that experiments done at this stage are based on best practice. This means both choosing the most appropriate animal model and doing the experiments in a way that ensures they are comparable and reproducible in different labs. This minimizes the risk of discarding a useful therapy, or conversely, taking a compound into trial in humans that is then proven to have no effect.
Where several animal models exist for one disease, selecting the most appropriate one maximizes the value of the experiments performed. Then, to ensure comparability and reproducibility of results from different labs, as many variables as possible in terms of animal handling and testing need to be controlled for. The variability in phenotype of laboratory animals, which is influenced by housing conditions, litter size, food composition and many other factors, needs to be minimized by the acceptance of common rules in animal handling. Similarly, the use of the same core set of endpoints in all preclinical efficacy studies facilitates the comparison of results.
All of these elements cannot be unilaterally dictated but require a consensus process to take place, with experts in the field coming together to agree on best practice. TREAT-NMD has held workshops with key scientists with expertise in animal models to reach a consensus and draw guidelines for a more harmonized, common effort in preclinical research. The results of this work for DMD and SMA are now available here on these pages, while the process is ongoing for CMD.