Researchers astudy pulsed sinusoidal electroporation for the treatment of glioblastoma

A team from Georgia Institute of Technology and Virginia Tech has published a paper in the journal APL Bioengineering that explores a new method that could one day be used to treat glioblastoma, a deadly and fast-growing brain tumor.
This work builds on previous research into high-frequency irreversible electroporation, better known as H-FIRE. H-FIRE is a minimally invasive process that uses non-thermal electrical pulses to destroy cancer cells. Treating any type of cancer is not easy, but when it comes to brain cancer, the blood-brain barrier poses an additional challenge. The blood-brain barrier protects the brain from toxic substances, but that's not always a positive thing.

"Mother Nature designed it to keep us from poisoning ourselves, but unfortunately it works in such a way that about 99% of all low molecular weight drugs don't reach the brain and don't reach concentrations high enough to show their therapeutic effects. This is especially true for chemotherapy, biologic drugs, or immunotherapy,” wrote the paper's authors, Dr. John Rossmeisl, MD, PhD, and the Dorsey Taylor Mahin Professor of Neurology and Neurosurgery at the Virginia-Maryland Dorsey College of Veterinary Medicine.

The square-shaped wave commonly used in H-FIRE serves a dual function: it disrupts the blood-brain barrier around the tumor site while destroying cancer cells. However, this was the first study to use a sine wave to break down the barrier.

This new method is called pulsed sinusoidal wave electroporation (B-SWE). The researchers used a rodent model to study the effect of the sine wave on the more traditional square wave. They found that B-SWE resulted in less cell and tissue damage, but more disruption of the blood-brain barrier.

In some clinical cases, both ablation and blood-brain barrier disruption would be ideal, but in other cases, disruption of the blood-brain barrier may be more important than cell destruction. For example, if a neurosurgeon has removed a visible tumor mass, the sinusoidal signal could potentially be used to disrupt the blood-brain barrier around that site, allowing drugs to penetrate the brain and destroy the last cancer cells. B-SWE can cause minimal damage to healthy brain tissue. Studies show that conventional rectangular signals are good at breaking down the blood-brain barrier, but this study shows that B-SWE is even better at breaking down the blood-brain barrier. This may allow more anti-cancer drugs to access the brain.

The scientists ran into a problem during the study: in addition to enhancing blood-brain barrier disruption, they found that the sine wave also causes an increase in neuromuscular contractions.

These muscle contractions can lead to organ damage. However, by changing the dose of B-SWE, they were able to reduce the contractions while providing a level of blood-brain barrier disruption similar to that of the higher dose. The next step in this study is to investigate the effects of B-SWE using an animal model of brain cancer to see how the sinusoidal waveform counteracts the traditional H-FIRE technique.

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