Nerinetide Analog NoNO-42: A Next-Generation Neuroprotectant for Acute Ischemic Stroke

1. Introduction to Nerinetide Analog NoNO-42

Nerinetide analog NoNO-42 is an investigational synthetic peptide currently under development by NoNO Inc. as a neuroprotective agent primarily targeting acute ischemic stroke (AIS).[1] This compound represents a second-generation therapeutic within NoNO Inc.'s Postsynaptic Density Protein-95 (PSD-95) inhibitor platform, building upon the research and clinical experience gained from its predecessor, nerinetide.[2] The principal driver for the development of NoNO-42 was the identification of a significant limitation with nerinetide: its efficacy was compromised in patients who had received thrombolytic therapy, specifically alteplase.[2] Consequently, NoNO-42 has been engineered for compatibility with thrombolytic agents, a critical advancement aimed at broadening the applicability of PSD-95 inhibition to a larger cohort of AIS patients.[1]

Acute ischemic stroke remains a leading global cause of death and long-term disability, imposing a substantial burden on individuals, families, and healthcare systems.[6] Despite advances in reperfusion therapies such as intravenous thrombolysis and endovascular thrombectomy (EVT), a significant unmet medical need persists for adjunctive neuroprotective treatments that can mitigate ischemic brain injury during the critical early hours following stroke onset. NoNO-42 seeks to fill this therapeutic gap.