Intravenous Immunoglobulin (IVIG) and Blood-Brain Barrier Disruption in Amyotrophic Lateral Sclerosis (ALS)

Original registry description

The goal of this study is to evaluate the safety and feasibility of IVIg administration in conjunction with primary motor cortex BBB opening using the Next Generation Dome Helmet (NGDH) FUS in adult participants with ALS.

This study is a prospective, single-arm, open-label, multiple-ascending dose (MAD), phase I trial to evaluate safety, feasibility, pharmacodynamics, and pharmacokinetics of enhanced delivery of IVIg 0.4 or 0.8g/kg to the primary motor cortex in 6 patients with ALS by using a single BBB opening procedure targeting the primary motor cortex in both brain hemispheres. Six participants will be enrolled in two sequential cohorts. The first cohort (n = 3) will receive 0.4g/kg of IVIg divided in two doses, while the second cohort (n = 3) will receive a 0.8g/kg of IVIg divided in two doses. In both cohorts, the second dose of IVIg will be accompanied by a single BBB opening procedure targeting the primary motor cortex in both brain hemispheres with focused ultrasound (FUS) using Next Generation Dome Helmet and intravenous microbubbles (DEFINITY®, Lantheus Medical Imaging Canada, Inc., Montreal, QC, Canada). This FUS procedure will occur during 2 weeks after the first dose administration. Follow-up visits will occur over the span of 24 weeks from the first dose.