Neurizon Therapeutics Limited announced 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 progressivedegeneration 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 S 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. 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 disorders. 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 company conviction in NUZ-001's potential as a disease-modifying platform therapy across a range of neurodegenerative conditions. 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 orNUZ-001 Sulf one at 1 and 10 mM concentrations were added to the embryonic media 6 hours post-fertilisation to evaluate the protective effects of NU Z-001 and NUZ-001 S Gulfone 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. Knockdown of Htt (Htt MO) resulted in zebrafish embryos with smaller eyes and swollen hindbrain ventricles.
Treatment with 1 mM and 10 mM NUZ-001, and 10 mM NUZ -001 Sulfone significantly significantly increased in the Htt knockdown zebrafish embryos compared to the control group. Treatment with 1 mM and10 mM NUZ-001 S sulphone significantly increased the Htt (Htt MO). Treatment with 1 mM and 10 million NUZ-001, & 10 mM NUZ-002 Sulfone significantly increased the number of neurodegenerative diseases.
