Melbourne-based company Neurizon Therapeutics has announced positive results from a preclinical study of its lead candidate, NUZ-001.
Amyotrophic Lateral Sclerosis (ALS) is a fatal type of motor neuron disease. It causes progressive degeneration of nerve cells in the spinal cord and brain.
The company said the studies revealed 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.
The company said it also revealed the ability of NUZ-001 to improve the electrophysiological dysfunction of TDP-43 M337V significantly mutated motor neurons.
Two preclinical studies were conducted with Ncardia, a leading human-induced pluripotent stem cell technology company.
The first study evaluated the ability of NUZ-001 and its major active metabolite to reduce TDP-43 aggregation in M337V Motor Neurons co-cultured with astrocytes in response to a stressor. TDP-43 is a known driver of ALS pathology. The results show that 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 per cent and 65 per cent, 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 associated with the development of ALS and has been shown to impair neuronal electrical activity at multiple levels. Neurizon said NUZ-001 and NUZ-001 Sulfone rescued the electrical activity of TDP-43 M337V Motor Neurons.
Neurizon managing director and CEO Dr Michael Thurn said, “The positive results from these preclinical studies are a significant milestone, providing validation of our hypothesis that NUZ-001 and its major metabolite prevent the damaging accumulation of TDP-43 in diseased neuronal cells. This finding also highlights the power of NUZ-001 to improve neuronal electrophysiology, an essential step towards providing patients with ALS with a meaningful treatment option.”
“This advancement brings us closer to delivering a much-needed therapeutic option for patients with ALS,” said Dr Thurn. “NUZ-001’s positive results present a compelling case for continued development and create exciting opportunities for partnerships as we advance our clinical studies. We are committed to making a significant difference in the lives of patients with ALS and are eager to move forward with our next clinical trial of NUZ-001 in early 2025.”