StrokeFM: The Future of Neuroprotection & The Story of Nerinetide with Dr. Michael HillEpisode S2_e07Is neuroprotection finally moving from "déjà vu" failure to clinical reality? In this episode, host Dr. Homan sits down with Dr. Michael Hill (University of Calgary) to dissect the fascinating journey of Nerinetide, the landmark ESCAPE-NA1 trial, and the biological detective work that uncovered why a potential breakthrough drug clashed with standard thrombolytics.The History of Failure: Why previous neuroprotection trials failed, primarily due to the lack of human-analogous ischemia-reperfusion models in pre-clinical testing.The Molecule: How Nerinetide works intracellularly by interfering with the PSD-95 protein to stop toxic nitric oxide production without blocking critical synaptic signaling.ESCAPE-NA1 Results: A deep dive into the trial that showed an overall neutral result (2% difference) but uncovered a massive, statistically significant benefit (approx. 9.5% absolute risk difference) in patients who did not receive Alteplase (tPA).The Plot Twist (The Interaction): The biochemical discovery that Alteplase cleaves and inactivates Nerinetide in human plasma—an interaction that was not present in rat models due to species differences in plasminogen activation.Biological Plausibility: How the creation of a "D-enantiomer" (a mirror image of the molecule) proved resistant to Alteplase cleavage, confirming the interaction theory.The Future: A look at ESCAPE-NEXT, the upcoming trial designed to replicate the successful "No-Alteplase" arm of the previous study, and the FRONTIER trial, which looks at pre-hospital administration."We essentially have a true human ischemia-reperfusion model... This is the number one difference between the possibilities that exist now compared to what we had done in the past." — Dr. Michael Hill"The trial was neutral... but when we looked at the two groups, we had a statistically relevant interaction... in the No-Alteplase group, the direction of effect was markedly positive." — Dr. Michael HillThe Trial: ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke)The Drug: Nerinetide (NA-1)Upcoming Trials: ESCAPE-NEXT and FRONTIERIn This Episode, We Discuss:Key Quotes:References & Further Reading:

Ver todos los episodios