Delivery of Arctiin via Ultrasound with Microbubbles Exerted Positive Effects on Motor Function in a Transgenic Mice Model of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease manifested by upper or lower motor neuron damage. Neuroinflammation has been increasingly recognized as an important mediator of disease progression in patients with ALS. Arctiin (Arc), which has been reported to have anti-inflammatory and neuronal protective functions, was used in this study to investigate its therapeutic effect on a mouse model of ALS. The delivery of Arc was enhanced by the blood–brain barrier (BBB) disruption via low-intensity focused ultrasound with microbubbles (FUS/MB). SOD1-G93A (SOD1) transgenic mice at an age of 13 weeks were used. Arc (40 mg/kg) was administered intraperitoneally every day for 6 weeks. BBB opening of the bilateral motor cortexes were performed twice per week for 6 weeks by FUS/MB. The decline magnitudes of the grip strength in the FUS/MB+Arc group were 5.4%, 7.7% and 13.7%, smaller than the ones in the Arc group (5.5%, 11.0% and 21.0%) when the treatments were conducted for 1 week, 3 weeks and 5 weeks. Both the Arc group and the FUS/MB+Arc group showed amelioration of motor neuronal degeneration in the ventral horn of spinal cord. These preliminary results indicated that potentially beneficial effect in neuromuscular function was induced by the combined treatment of Arc and FUS/MB.