Neurizon’s NUZ-001 Reduces Aggregation of Key ALS Disease Target TDP-43 in Preclinical Study By Investing.com

Highlights:

• Positive preclinical results in human in vitro iPSC Motor Neuron models of Amyotrophic Lateral Sclerosis (ALS)
• Neurizon’s lead drug NUZ-001 and its major active metabolite significantly and dose-dependently prevented the aggregation of TAR DNA-binding protein 43 (TDP-43) by ~50% and ~55% respectively, in M337V Motor Neurons in response to a stressor
• TDP-43 aggregation is a key hallmark pathological feature of ALS
• Treatment with NUZ-001 and its major metabolite significantly improved electrophysiological dysfunction of TDP-43 mutated M337V Motor Neurons
• Provides valuable insights into the mechanism of action of NUZ-001 in ALS and strengthens promising efficacy results from the Phase 1 MEND study completed earlier this year in patients with ALS

MELBOURNE, Australia, Nov. 19, 2024 /PRNewswire/ — Neurizon Therapeutics Limited (ASX: NUZ & NUZOA) (“Neurizon” or “the Company”), a clinical-stage biotech company advancing treatments for neurodegenerative diseases, is pleased to announce positive results from a preclinical study of its lead candidate, NUZ-001. These innovative studies reveal NUZ-001’s unique mechanism of action in preventing the aggregation of TAR DNA-binding protein 43 (TDP-43), a key pathological feature of ALS, and the ability of NUZ-001 to significantly improve the electrophysiological dysfunction of TDP-43 M337V mutated  motor neurons, showcasing the potential for NUZ-001 to be a transformative treatment for ALS. Importantly, these findings reinforce the promising efficacy results seen in Neurizon’s Phase 1 MEND study and bolster confidence in NUZ-001 therapeutic capabilities for patients with ALS.

Two separate preclinical studies were conducted in collaboration with Ncardia, a leading human induced pluripotent stem cell (iPSC) technology company. The first  study evaluated the ability of NUZ-001 and its major active metabolite (NUZ-001 Sulfone) to reduce TDP-43 aggregation in M337V Motor Neurons co-cultured with astrocytes in response to a stressor. TAR DNA-binding protein 43 (TDP-43) is a known driver of ALS pathology. The results show NUZ-001 and NUZ-001 Sulfone significantly and dose-dependently reduced TDP-43 aggregation in M337V Motor Neurons treated simultaneously with aggregation stressor MG-132 by ~50% and ~55%, respectively.

The second study evaluated the ability of NUZ-001 and NUZ-001 Sulfone to restore the normal electrophysiological function of TDP-43 mutated M337V  Motor Neurons. The TDP-43 M337V mutation is…