MILAN and MORRISTOWN, N.J. — Preclinical research published in Neuropsychopharmacology suggests that evenamide, an experimental glutamate modulator from Newron Pharmaceuticals, may address multiple symptom domains of schizophrenia by targeting hyperactivity in the hippocampus, a key site of disease pathology.
The study, led by researchers at the University of Pittsburgh using the methylazoxymethanol acetate (MAM) neurodevelopmental model of schizophrenia, found that acute administration of evenamide improved positive, negative, and cognitive symptoms. Effects from a single dose lasted beyond the drug’s elimination, indicating a possible influence on neuronal plasticity.
“The study examined the effect of acute evenamide treatment on the hyperdopaminergic state, hippocampal hyperexcitability, social deficits, and recognition memory in the MAM model,” said Daniela L. Uliana, first author and researcher in the university’s Departments of Neuroscience, Psychiatry, and Psychology. She explained that the MAM model reproduces many structural, behavioral, and neurochemical changes associated with the disorder.
Senior author Dr. Anthony A. Grace said the findings point to a different therapeutic approach than existing dopamine D2 antagonist-based antipsychotics. “Evenamide is a unique NCE agent in acting at the site of the deficit in schizophrenia by reducing hippocampal hyperexcitability,” he said. “This represents a significant advancement in treatment, as evenamide can downregulate the hyperdopaminergic state without producing D2 blockade-related side effects while also improving behavioral deficits that are not properly treated by D2 blocking antipsychotic agents.”
Grace noted that the recognition memory improvement observed in the MAM model “may indicate that it may also enhance cognitive function in patients with schizophrenia and ultimately lead to a better functional outcome.” Current antipsychotics, he added, do not effectively address cognitive symptoms, which remain a major factor in patients’ quality of life.
Newron Chief Medical Officer Ravi Anand said the preclinical findings align with earlier clinical trial results, including improvements observed in treatment-resistant patients in Phase 2 and Phase 3 studies. “The prolonged effect in the MAM model explains the continuing improvement in symptoms even one year after starting treatment with evenamide in TRS patients in our Phase 2 trial,” Anand said. He added that the ongoing pivotal Phase 3 program aims to confirm the drug’s potential as part of a “completely new treatment paradigm” for schizophrenia.
