This is not a new story and at least some of our readers may be familiar with the conflicting results regarding the presence of a GABA-A positive modulating substance in the CSF of patients with daytime sleepiness. Of note, GABA-A receptor potentiating effects of the patients’ CSF is established using conventional electrophysiological methods characterized by a variety of details critical for observing the positive allosteric modulation (as opposed to the direct stimulation of a receptor by agonists).
Now, a new report appeared in Annals of Neurology from a lab whose original data has been challenged by another group that could not confirm such a positive modulating effect. Here, Olivia Moody and colleagues point out critical aspects of experimental design that account for the reported differences. Additionally, they present new data demonstrating the robustness and reproducibility of their original findings. This paper is worth reading for several reasons. First, it is an example of replication efforts that have direct impact on the development of a novel therapeutic(s) (i.e. for patients with hypersomnolence). Second, it is an excellent illustration of the importance of methodological details to avoid unsuccessful replication efforts. And last, but certainly not least, it is a remarkable example of the shared responsibility between authors of original reports and scientists attempting to replicate it. It clearly shows the necessity to disclose as many details as possible and to initiate an effective communication between the research teams before any unsuccessful replication efforts are published. As striking as it may be in this particular case, these two groups chose Annals of Neurology for communication and there is nothing said in either of the papers about direct contacts and attempts to resolve the controversy.