The Frustration of ALS Therapy Development

In the search for potential treatments for amyotrophic lateral sclerosis (ALS), researchers previously identified ceftriaxone, a beta-lactam antibiotic that increases glutamate transporter activity, from a blinded screen of 1040 FDA-approved drugs and nutritionals based on expression of the glutamate transporter in rat spinal cord slice cultures. Validation studies included an assessment of preclinical efficacy in the SOD1 mouse model of ALS, showing prevention of motor neuron loss and prolonged survival. These data launched a multicenter clinical trial that proceeded in three stages. Based on pharmacokinetic (stage 1), and safety/ tolerability (stage 2) data, researchers now report findings from stage 3, in which 514 patients were randomiz…