A phase Ib/IIa study of Enoxacin in patients with ALS

Abstract

AbstractThe RNAse III DICER is essential for miRNA biogenesis. DICER activity is downregulated in sporadic and genetic forms of ALS. Accordingly, hundreds of miRNAs are broadly downregulated, and their mRNA targets are de-repressed. Enoxacin is a fluoroquinolone, which increases DICER activity and miRNA biogenesis. In an investigator-initiated, first-in-patient phase Ib/IIa study we tested Enoxacin safety and tolerability in patients with ALS and explored pharmacodynamic biomarkers for Enoxacin target engagement. Six patients with sporadic ALS were dosed with oral Enoxacin twice daily for 30 days. Patients did not experience any serious adverse events and completed the dosing period. Molecular analysis of cell-free miRNA in plasma and CSF revealed a global increase in plasma and CSF miRNA levels in all post-treatment time points, compared to baseline. Therefore, our study demonstrates that Enoxacin is tolerable and provides important evidence for in-patient target engagement. These results encourage testing Enoxacin efficacy in larger trials.