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

ABSTRACT:

Objective

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.

Methods

The study included placebo-controlled, single and multiple ascending-dose (SAD; MAD) stages, and an open-label safety expansion (OLE) with adaptive dosing for up to 48 weeks.

Results

Forty-nine patients were enrolled. GDC-0134 (up to 1200 mg daily) was well

SUBMITTER: Katz JS 

PROVIDER: S-EPMC8791798 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature