Recently published preclinical data about an N-methyl-D-aspartate (NMDA) receptor modulator by clinical-stage biopharmaceutical company Aptinyx Inc shows positive results on sleep.
In a Sleep journal article, “NMDAR activation regulates the daily rhythms of sleep and mood,” the data demonstrates the positive activity exhibited by Evanston, Ill-based Aptinyx’s NMDA modulator NYX-2925 on various elements of sleep architecture.
- Administration of NYX-2925 enhanced sleep quality, as measured by an increase in the non-REM component of sleep.
- NYX-2925 facilitated an increase in sleep-bout duration and decreased drowsiness during wake, as measured by delta power.
- NYX-2925 also reversed sleep deprivation-induced deficits in a learning task and improved mood.
Aptinyx has also conducted a translational sleep study in humans based on these observations on sleep parameters and NYX-2925 demonstrated significant effects on multiple sleep measures, including an increase in non-REM sleep, in that study as well. NMDA receptor-dependent synaptic plasticity processes are critical for sleep regulation and disrupted sleep is known to occur in a number of disorders, including chronic pain. These data support continued exploration of the effect of positive NMDA receptor modulation on sleep quality and associated downstream behavioral changes in both preclinical and clinical models.
NYX-2925 is a novel oral NMDA receptor modulator currently in Phase 2 clinical development for the treatment of chronic pain. The US Food and Drug Administration has granted Fast Track designation to Aptinyx’s development of NYX-2925 for the treatment of neuropathic pain associated with diabetic peripheral neuropathy.
Other recent publications about NYX-2925 include:
- “NYX‐2925 induces metabotropic NMDAR signaling that enhances synaptic NMDAR and AMPAR” and has been published in the Journal of Neurochemistry. The data published in this paper detail the NYX-2925 treatment-mediated increases in NMDA receptor GluN2B trafficking and long-term potentiation-related signaling. The findings demonstrate the facilitation of synaptic plasticity processes resulting from administration of different concentration levels of NYX-2925.
- “A translational EEG-based approach to assess modulation of long-lasting NMDAR-dependent synaptic plasticity” and has been published in Psychopharmacology. Oral administration of NYX-2925 enhanced alpha power, increased NMDA receptor-dependent auditory LTP, and facilitated NMDA receptor-dependent mismatch negativity. The published studies are the first in vivo demonstration of the long-lasting effects of positive NMDA receptor modulation on synaptic plasticity processes using non-invasive EEG techniques. Aptinyx has also conducted a translational EEG study in healthy human volunteers in which NYX-2925 was shown to facilitate mismatch negativity and enhance synaptic plasticity, demonstrating that the mechanistic activity observed preclinically is consistent with the activity observed in the human brain.
“The data published in these journals are reflective of our in-depth understanding of the activity of NYX-2925, garnered through evaluations across numerous molecular and behavioral preclinical models,” says Norbert Riedel, PhD, president and CEO of Aptinyx, in a release. “NYX-2925 and other compounds in our pipeline are highly selective to the NMDA receptor and exhibit a unique modulatory mechanism of action on this receptor. We are very pleased to have these data published across these high-caliber peer-reviewed journals to enhance the understanding of this novel mechanism, which is highly relevant in the treatment of chronic centralized neuropathic pain as well as other neurologic conditions caused by aberrant synaptic plasticity processes.”