First-in-human trial of blood-brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound

Nat Commun. 2019 Sep 26;10(1):4373. doi: 10.1038/s41467-019-12426-9.


MR-guided focused ultrasound (MRgFUS) is an emerging technology that can accurately and transiently permeabilize the blood-brain barrier (BBB) for targeted drug delivery to the central nervous system. We conducted a single-arm, first-in-human trial to investigate the safety and feasibility of MRgFUS-induced BBB opening in eloquent primary motor cortex in four volunteers with amyotrophic lateral sclerosis (ALS). Here, we show successful BBB opening using MRgFUS as demonstrated by gadolinium leakage at the target site immediately after sonication in all subjects, which normalized 24 hours later. The procedure was well-tolerated with no serious clinical, radiologic or electroencephalographic adverse events. This study demonstrates that non-invasive BBB permeabilization over the motor cortex using MRgFUS is safe, feasible, and reversible in ALS subjects. In future, MRgFUS can be coupled with promising therapeutics providing a targeted delivery platform in ALS.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyotrophic Lateral Sclerosis / diagnostic imaging*
  • Amyotrophic Lateral Sclerosis / drug therapy
  • Anesthetics, Intravenous / administration & dosage
  • Blood-Brain Barrier / diagnostic imaging*
  • Blood-Brain Barrier / physiology
  • Brain / diagnostic imaging*
  • Drug Delivery Systems / methods
  • Feasibility Studies
  • Female
  • Fentanyl / administration & dosage
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Midazolam / administration & dosage
  • Middle Aged
  • Prospective Studies
  • Ultrasonography / methods*


  • Anesthetics, Intravenous
  • Midazolam
  • Fentanyl