Preclinical & Early Clinical Development of NUZ-001: A Novel mTOR Inhibitor Demonstrating Potential as a Therapeutic Agent for Amyotrophic Lateral Sclerosis
Time: 2:30 pm
day: Conference Day Two PM
Details:
• ALS and related TDP-43 proteinopathies are driven by the mislocalization and aggregation of TDP-43, leading to neurodegeneration; the concurrent loss of Stathmin-2 (STMN2), a key regulator of axonal repair, further accelerates disease progression and highlights the need for therapies targeting both TDP43 pathology and STMN2 restoration
• NUZ-001, a novel small-molecule mTOR inhibitor, is under investigation for its ability to reduce TDP-43 aggregation, restore STMN2 expression, and enhance autophagy—a critical protein clearance pathway—offering a multi-targeted approach to disease modification in ALS
• Preclinical studies using human iPSC-derived motor neurons showed that NUZ-001 significantly decreased cytoplasmic TDP-43 aggregation, increased STMN2 protein levels, and activated autophagy as indicated by elevated p62 accumulation and LC3 vesicle formation; functional assays further demonstrated neuroprotective effects including enhanced neurite outgrowth and preserved motor function
• Preliminary results from a Phase 1 clinical trial in ALS patients indicated that NUZ-001 is well tolerated with a favorable safety profile and pharmacokinetics, alongside early signs of efficacy and biomarker modulation, supporting further clinical development to explore its potential as a disease-modifying therapy
