Spinal cord and brain concentrations of riluzole after oral and intrathecal administration: A potential new treatment route for amyotrophic lateral sclerosis

• DOI: 10.1371/journal.pone.0277718
• Publication Date: 2023-08-22T17:30:06Z
• Authors: Orion P. Keifer; Juanmarco Gutierrez; Mark T. Butt; Sarah D. Cramer; Raymond Bartus; Malu Tansey; Daniel Deaver; Alexandre Betourne; Nicholas M. Boulis
• Keywords: Riluzole; Tolerability

Riluzole is the only treatment known to improve survival in patients with Amyotrophic Lateral Sclerosis (ALS). However, oral riluzole efficacy modest at best, further it have large inter-individual variability of serum concentration and clearance, formulated as an drug a patient population plagued dysphagia, has systemic side-effects like asthenia (limiting compliance) elevated liver enzymes. In this context, we postulated that continuous intrathecal (IT) infusion low doses could provide consistent elevations spinal cord (SC) concentrations or above those achieved dosing, without increasing risk for adverse events associated exposure off-target side effects brain. We developed formulation IT delivery conducted our studies purpose-bred hound dogs. Our non-GLP revealed alone was able increase SC provided by administration, plasma concentrations. then two GLP combined administration human equivalent dose, evaluate brain along assessments safety tolerability. 6-week study, highest dose (0.2 mg/hr) well tolerated animals increased alone, 6-month tested (0.4 not yielded significantly all previous studies. data show feasibility profile cord, concurrent enzymes, minimal creating another potential therapeutic route be used isolation combination other therapeutics."