NLS Pharmaceutics Ltd. announced preclinical results from multiple in vitro studies targeting alpha-synuclein (a-synuclein), specifically the A53T mutation, that demonstrate the compounds' potential to advance the treatment of Parkinson's Disease (PD). The compounds may be used by NLS pursuant to its existing and previously announced license agreement with Aexon Labs Inc. (Aexon Labs or AEX). Using the "Alpha-Synuclein (a-synuclein) A53T Parkinson's Disease Genetic Cell-Based Agonist Neurite Outgrowth Assay" by Eurofins, various DOXA compounds demonstrated positive effects on neurite outgrowth, a critical parameter of neuronal health and regeneration.

Neurite outgrowth, a critical parameter of neuronal health, was measured using high-content imaging systems to determine the efficacy of AEX compounds. Reducing a-synuclein aggregation or promoting its clearance can alleviate its toxic effects on neurons. The effects of AEX compounds on neurite outgrowth as well as their impact on Cathepsin D (CTSD) and Orexin 1 Receptor (OX1R) activities provide insights into their potential to modulate the impact of a-synuclein.

Key findings: AEX-23: Its pronounced action as an OX1R agonist combined with positive effects on neurite outgrowth at specific concentrations suggests that it may modulate neuronal health through pathways influencing a-synuclein dynamics, making it a potential therapeutic candidate to improve neuronal connectivity and resilience in PD. AEX-19: Its effects at low concentrations on neurite growth coupled with OX1R agonist activity and a moderate increase in CTSD activity suggest potential neuroprotective benefits in PD. AEX-24: The increase in CTSD activity and agonist activity on OX1R suggests the potential to enhance a-synuclein degradation, highlighting its promising therapeutic impact on PD.

AEX-23 and AEX-19, which target OX1R, show promise in modulating the effects of a-synuclein on neurons, offering potential benefits in treating synucleinopathies like PD. AEX-19 and AEX-24 also present intriguing possibilities due to their effects on CTSD activity, suggesting pathways for reducing a-synuclein aggregation. Further in vitro research and in vivo preclinical studies are necessary to elucidate the precise mechanisms, optimize dosing, and evaluate the long-term efficacy and safety of these compounds in preclinical and clinical settings.