Pathology reduction and motor behavior improvement associated with ultrasound-mediated delivery of arctiin to the motor cortex in a mutant SOD1 mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is marked by the deterioration of both cortical and spinal cord motor neurons. Despite the underlying causes of the disease remain elusive, there has been a growing attention on the well-being of cortical motor neurons in recent times. Focused ultrasound combined with microbubbles (FUS/MB) for opening the blood-brain barrier (BBB) provides a means for drug delivery to specific brain regions, holding significant promise for the treatment of neurological disorders. We aim to explore the outcomes of FUS/MB-mediated delivery of arctiin (Arc), a natural compound with anti-inflammatory activities, to the cerebral motor cortex area by using a transgenic ALS mouse model. The ALS mouse model with the SOD1^G93A mutation was used and subjected to daily Arc administration with FUS/MB treatment twice a week. After six-week treatments, the motor performance was assessed by grip strength, wire hanging, and climbing-pole tests. Mouse brains, spinal cords and gastrocnemius muscle were harvested for histological staining. Compared with the mice given Arc administration only, the combined treatments of FUS/MB with Arc induced further mitigation of the motor function decline, accompanied by improved health of the gastrocnemius muscle. Furthermore, notable neuroprotective effect was evidenced by the amelioration of motor neuron failure in the cortex and lumbar spinal cord. These preliminary results indicated that the combined treatment of FUS/MB and arctiin exerted a potentially beneficial effect on neuromuscular function in the ALS disease.