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A Phase 1 study of GDC‐0134, a dual leucine zipper kinase inhibitor, in ALS

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Dual leucine zipper kinase (DLK), which regulates the c‐Jun N‐terminal kinase pathway involved in axon degeneration and apoptosis following neuronal injury, is a potential therapeutic target in amyotrophic lateral sclerosis… Click to show full abstract

Dual leucine zipper kinase (DLK), which regulates the c‐Jun N‐terminal kinase pathway involved in axon degeneration and apoptosis following neuronal injury, is a potential therapeutic target in amyotrophic lateral sclerosis (ALS). This first‐in‐human study investigated safety, tolerability, and pharmacokinetics (PK) of oral GDC‐0134, a small‐molecule DLK inhibitor. Plasma neurofilament light chain (NFL) levels were explored in GDC‐0134‐treated ALS patients and DLK conditional knockout (cKO) mice.

Keywords: dual leucine; zipper kinase; kinase; gdc 0134; leucine zipper

Journal Title: Annals of Clinical and Translational Neurology
Year Published: 2022

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