Focused Ultrasound Makes Anti-Epileptic Drug More Effective in Preclinical Study


Key Points

  • Researchers have developed a new method to improve the treatment of epilepsy using focused ultrasound. 
  • Focused ultrasound increased the effectiveness of an anti-epilepsy drug by blocking the drug from binding to a protein that inhibits it from entering the brain. 
  • The preclinical experiments produced fewer seizures and shorter duration of seizure activity. 
Medical illustration of a brain

Transcranial Focused Ultrasound–Mediated Unbinding of Phenytoin from Plasma Proteins for Suppression of Chronic Temporal Lobe Epilepsy in a Rodent Model 

Researchers based at Brigham and Women’s Hospital (BWH) and Harvard Medical School used focused ultrasound to develop an interesting new method to improve the treatment of epilepsy. Specifically, they increased the effectiveness while decreasing the side effects of an anti-epilepsy drug called phenytoin (PHT) by using focused ultrasound to disrupt the binding of PHT to albumin within the bloodstream. Albumin is a protein in the blood that binds to PHT and prevents it from crossing the blood-brain barrier (BBB) and entering the brain. When PHT is unbound, it is small enough to cross the BBB, but having high systemic levels of PHT in the body creates serious side effects, such as liver damage, impaired coordination, and suicidal thoughts. 

Together with their team, Seung-Schik Yoo, PhD, and Wonhye Lee, PhD, faculty in the Neuromodulation and Tissue Engineering Laboratory in the Department of Radiology at BWH and Harvard University, conducted preclinical experiments to determine the proper acoustic parameters and then treated rats with chronic mesial temporal lobe epilepsy. When compared with untreated subjects, those that received four sessions of PHT injection followed by 30 minutes of focused ultrasound delivered to the ictal region over a 2-week treatment period had fewer seizures and shorter duration of seizure activity without causing damage. 

“None of the animals showed the modified Racine’s scale 3–5 seizures during the period of PHT treatments combined with focused ultrasound, whereas a number of rats (2–3 out of 10 animals in each group) showed tonic–clonic seizures during the interventions of PHT only or focused ultrasound alone,” said the article. “These results support the capability of focused ultrasound to enhance the therapeutic efficacy of PHT on the suppression of behavioral seizures, which agreed with reductions of the electrographic ictal activities.” 

The miniature, single-element focused ultrasound transducer used to apply low-intensity energy in the experiments was built in the group’s Neuromodulation and Tissue Engineering Laboratory. If translatable to humans, the use of focused ultrasound to deliver PHT in a specific region of the body, especially the brain, and reduce serious systemic side effects could potentially increase the efficacy of PHT as a therapy for epilepsy. 

See Scientific Reports