Highlights:
NUZ-001 and its active metabolite NUZ-001 Sulfone demonstrated significant neuroprotective effects in a zebrafish model of Huntington’s disease
Treatment prevented hallmark developmental and morphological abnormalities, protected against neuronal cell death, restored delayed haemoglobin production, and rescued BDNF expression following Htt protein knockdown
Neurizon plans to initiate additional validation studies in mammalian models of Huntington’s disease
These findings reinforce NUZ-001’s potential as a platform therapy targeting core neurodegenerative mechanisms
Neurizon® Therapeutics Limited(ASX: NUZ & NUZOA) (“Neurizon” or “the Company”), a clinical-stage biotech company dedicated to advancing innovative treatments for neurodegenerative diseases, is pleased to announce new preclinical data demonstrating significant neuroprotective effects of NUZ-001 and its active metabolite, NUZ-001 Sulfone, in a zebrafish model of Huntington’s disease (HD). HD is a rare, inherited neurodegenerative disorder that causes progressive degeneration of motor function, cognition, and mental health.
In this disease model of HD, the targeted knockdown of the Htt (huntingtin) protein mRNA knockdown approach, triggers characteristic HD-related deficits, including increased cell death (acridine orange staining), morphological malformations, impaired haemoglobin production (Benzidine staining), and reduced expression of brain-derived neurotrophic factor (BDNF), a critical biomarker of neuronal function and survival. Treatment with NUZ-001 or NUZ-001 Sulfone following Htt knockdown prevented developmental and morphological abnormalities, attenuated neuronal cell death, restored the delayed production of haemoglobin, and rescued BDNF expression, providing evidence of their potential to counteract early neurodegenerative damage.
Dr. Michael Thurn,Managing Director and Chief Executive Officer, commented:“These results mark another important milestone in the realisation of the potential for NUZ-001 to treat a range of neurodegenerative diseases. HD is a devastating, rare genetic disorder that causes the progressive breakdown of nerve cells in the brain, leading to a range of symptoms including uncontrolled movements, cognitive decline, and emotional disturbances. HD affects between 2.7 and 4.8 per 100,000 people globally. There is no cure and no disease-modifying treatments, only treatments that manage symptoms. These exciting results demonstrate NUZ-001 has consistent neuroprotective effects beyond amyotrophic lateral sclerosis (ALS), strengthening our conviction in NUZ-001’s potential as a disease-modifying platform therapy across a range of neurodegenerative conditions.”
About the Zebrafish Disease Model
Wild-type zebrafish embryos were raised in standard conditions. Morpholino antisense oligonucleotides (MOs) targeting Htt were injected into one-cell stage embryos to decrease Htt expression. NUZ-001 or NUZ-001 Sulfone at 1 and 10 μM concentrations were added to the embryonic media 6 hours post-fertilisation to evaluate the protective effects of NUZ-001 and NUZ-001 Sulfone on Htt knockdown-induced deficits. Changes in morphology (eye size and hindbrain swelling), neuronal cell death (apoptosis), and the levels of BDNF expression were analysed 2 days post-fertilisation (See Figure 1).
Figure 1: Htt knockdown and treatment procedure
For high resolution please click the image.
Knockdown of Htt (Htt MO) resulted in zebrafish embryos with smaller eyes and swollen hindbrain ventricles (See Figure 2a; arrows indicate hindbrain and eye regions) compared to the control group (Control MO). Partial rescue of eye size was observed following treatment with 1 μM and 10 μM NUZ-001 and NUZ-001 Sulfone, with full reversal of hind brain swelling at 10 μM NUZ-001 and NUZ-001 Sulfone. (Fi...
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