“Traumatic brain injury often results in cognitive impairment and mood disturbances that have a significant impact on a person’s daily living and, unfortunately, there are very few treatment options available today to address these long-term effects adequately,” said
The presented studies evaluated the effects of NYX-458 in a repeat closed head injury preclinical model. The cognitive and emotional deficits observed in the model are reflective of those observed in humans that have experienced repeated traumatic brain injury. In addition to evaluating behavioral effects, this model enables the evaluation of biomarkers, including protein and hormone changes, also associated with head injury.
Cognitive Performance Observations:
To evaluate the behavioral effects of NYX-458, two different models were used to observe performance on both spatial and affective learning tasks in rodents. In both models, Y-Maze and Positive Emotional Learning, performance was significantly impaired following repeat closed head injury.
The presented data show that repeat closed head injury resulted in activation of glial fibrillary acidic proteins (GFAP); mirroring data found in other traumatic brain injury models. Closed head injury also resulted in transient decreases in GluN2A and GluN2B subunits of the NMDA receptor. NYX-458, which has been shown preclinically to positively modulate NMDA receptors, may be well suited to address this observed NMDA receptor hypofunction, warranting further preclinical and clinical evaluation.
Neuroendocrine changes, including reduced growth hormone and increased corticosterone levels, were also observed following repeat closed head injury. In the model presented, NYX-458 administration restored normal levels of corticosterone and growth hormone.
Overall, the presented cognitive behavioral and biomarker data further support the evaluation of NYX-458 in human clinical studies in cognitive impairment. The results indicate the potential utility of NYX-458 in addressing both the cognitive impairment and the underlying disease processes associated with repeated traumatic brain injury and other neurodegenerative conditions.
Poster Presentation Details:
Presentation Title: A Novel NMDA Receptor Modulator, NYX-458, Shows Therapeutic Potential for Cognitive Impairment Associated with TBI in Rats (Poster Number: 498)
NYX-458 is a novel oral NMDA receptor modulator currently in clinical development for the treatment of cognitive impairment associated with Parkinson’s disease. NYX-458 has been shown to reverse cognitive deficits in non-human primates in a model that is highly translatable to Parkinson’s disease in humans. Additionally, NYX-458 has been shown to improve cognitive performance across various models of neurodegeneration. In a Phase 1 clinical study, NYX-458 exhibited a favorable safety and tolerability profile across a wide dose range and achieved CNS exposure in line with exposure observed with efficacious preclinical dose levels.
Aptinyx Inc. is a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of proprietary synthetic small molecules for the treatment of brain and nervous system disorders. Aptinyx has a platform for discovery of novel compounds that work through a unique mechanism to modulate—rather than block or over-activate—NMDA receptors and enhance synaptic plasticity, the foundation of neural cell communication. The company has three product candidates in clinical development in central nervous system indications, including chronic pain, post-traumatic stress disorder, and cognitive impairment associated with Parkinson’s disease. Aptinyx is also advancing additional compounds from its proprietary discovery platform, which continues to generate a rich and diverse pipeline of small-molecule NMDA receptor modulators with the potential to treat an array of neurologic disorders. For more information, visit www.aptinyx.com.
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Source: Aptinyx Inc.