Neurizon Therapeutics Limited has announced promising preclinical data showing that its lead drug candidate NUZ-001 and its active metabolite NUZ-001 Sulfone demonstrated significant neuroprotective effects in a zebrafish model of Huntington's disease (HD). The findings represent a potential expansion of the therapy's applications beyond amyotrophic lateral sclerosis (ALS), where it is currently in clinical development.
Zebrafish Model Results Show Multiple Protective Effects
In the HD disease model, researchers used morpholino antisense oligonucleotides to knock down the huntingtin (Htt) protein in zebrafish embryos, triggering characteristic HD-related deficits including increased cell death, morphological malformations, impaired haemoglobin production, and reduced expression of brain-derived neurotrophic factor (BDNF).
Treatment with NUZ-001 or NUZ-001 Sulfone at concentrations of 1 and 10 μM prevented developmental and morphological abnormalities, attenuated neuronal cell death, restored delayed haemoglobin production, and rescued BDNF expression. The compounds showed dose-dependent effects, with 10 μM concentrations providing full reversal of hindbrain swelling and significant rescue of BDNF expression.
"These results mark another important milestone in the realisation of the potential for NUZ-001 to treat a range of neurodegenerative diseases," said Dr. Michael Thurn, Managing Director and Chief Executive Officer of Neurizon. "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."
Addressing Significant Unmet Medical Need
Huntington's disease affects between 2.7 and 4.8 per 100,000 people globally and is caused by a CAG trinucleotide repeat expansion in the Htt gene, leading to production of a mutant huntingtin protein with an abnormally long polyglutamine tract. This mutant protein misfolds and forms toxic aggregates in neurons, particularly in the striatum and cortex, disrupting cellular functions and ultimately leading to neuronal dysfunction and death.
The disease typically manifests between ages 30 and 50, progressing over 15 to 20 years with gradual decline in motor function, cognition, and mental health. Currently, no approved therapies modify the underlying disease progression, with treatment approaches focusing only on symptom management through dopamine-depleting agents for chorea and psychiatric medications for behavioral symptoms.
Platform Therapy Potential
NUZ-001 is currently in clinical development for ALS, where it has shown preclinical efficacy in enhancing proteostasis, reducing pathological protein aggregation, and preserving neuronal function. The new HD findings underscore the compound's potential as a platform therapy targeting fundamental cellular stress and clearance mechanisms common to multiple neurodegenerative diseases.
The company plans to advance additional preclinical studies in mammalian models of Huntington's disease as part of its broader strategy to expand NUZ-001's therapeutic applications into other progressive neurological disorders with high unmet medical need.
