Gene Therapy Trial Targets Seizures That Medicine Can’t Stop

A Rutgers and RWJBarnabas Health neurosurgeon leads testing on whether a one-time treatment can quiet seizure circuits without harming brain tissue

A chef named Colton Beschen came to Robert Wood Johnson University Hospital one Tuesday in April to see if an experimental gene therapy could restore the life that epilepsy stole from him.

Rutgers professor and neurosurgeon Robert Gross drilled a hole the width of a pencil lead into Beschen's skull, threaded a catheter into the deep middle of his brain and slowly infused a few drops of a genetically altered virus.

Beschen went home the next day feeling no pain, lacking no hair, bearing no visible scars and hoping his life would soon go back to normal.

I am seeking to show that this gene therapy works as designed. If so, it will reduce or eliminate seizures without damaging brain tissue.

Robert Gross

Chair, Dept. of Neurological Surgery, Rutgers Robert Wood Johnson Medical School, Senior VP of Neurosurgery, RWJBarnabas Health

The 36-year-old is one of the first people in the world to receive AMT-260, an investigational gene therapy designed to silence a single misbehaving receptor in the brain that triggers seizures. If the approach works, it will be the first gene therapy ever offered for epilepsy.

Pharmaceutical companies have been developing epilepsy treatments for many decades, but according to the Centers for Disease Control and Prevention, about a third of the 2.9 million adults in the United States with active epilepsy never respond fully to medication.

"I'm a chef by trade, and I had several episodes while I was at work in the kitchen," said Beschen, who can't drive or live alone and hasn't worked in two years. "It was a very tight space. It's a miracle I didn't injure myself in some incredibly gruesome way before I finally left the job."

Existing surgical treatments for medication-resistant temporal lobe epilepsy, such as Beschen's, can stop seizures for many patients by destroying the tissue where seizures start, either by removing it outright or by burning it with a laser. Unfortunately, both procedures damage working parts of the brain and can hurt memory, language, vision or all three.

"Many patients decline surgery because they'd rather live with seizures than risk significant memory loss," said Gross, who chairs the Department of Neurological Surgery at Rutgers Robert Wood Johnson Medical School and is senior vice president of Neurosurgery at RWJBarnabas Health. "As the site principal investigator for the AMT-260 trial, I am seeking to show that this gene therapy works as designed. If so, it will reduce or eliminate seizures without damaging brain tissue."

AMT-260, which has been licensed by the Dutch company uniQure NV after initial development in French academia, uses a virus that has been stripped of its own genetic code and refilled with a short stretch of inhibitory RNA to alter brain biology without changing brain-cell DNA. A single dose aims to create a self-sustaining loop of genetic material that suppresses the production of a glutamate receptor called GluK2, which is one of the molecular drivers of seizures in mesial temporal lobe epilepsy.

Because the treatment aims to suppress the formation of new receptors rather than kill existing ones, Beschen will have to wait several months to know what effects, if any, it will have on his seizures.

"It's hard to describe the feeling, having to wait months to know if a treatment that's already complete will work," said Beschen, who typically has several seizures a day, often without noticing any of the signs that would be obvious to any onlooker. His speaking slows. His body tenses. But unlike the rarer "grand mal" seizures that involve violent shaking and loss of consciousness, these smaller episodes make no impression on him. "I take comfort in knowing that if this fails, the standard surgical treatments are still open to me."

Beschen is part of a study that's primarily designed to establish AMT-260's safety and tolerability in roughly a dozen patients. Even if all those patients achieve total cures, a larger randomized controlled study would be needed to establish the general effectiveness.

Rutgers and RWJBarnabas Health, whose Robert Wood Johnson University Hospital is its flagship academic medical center with faculty from Robert Wood Johnson Medical School, participate in clinical trials of many new medical technologies and procedures, as such tests give their clinicians and researchers hands-on experience with and their patients access to cutting-edge treatments.

I think this is the dawn of something totally new. It is an incredibly exciting time to be doing this.

Robert Gross

Participating in gene therapy trials was an explicit priority that Rutgers announced last year after the National Institutes of Health awarded $39.7 million to a Rutgers-led translational science consortium. Moreover, Gross had run gene-therapy trials for Parkinson's disease at Emory University before Rutgers and RWJBarnabas Health recruited him in 2023 to lead neurological surgery.

The medical school's focus on gene therapy stems from the hope that it may prove transformational in the treatment of many diseases, including many poorly controlled neurological conditions. Such therapies are in clinical testing or late-stage development for Huntington's disease, Parkinson's, dystonia, certain psychiatric disorders, Alzheimer's and substance use disorder.

The first and only such treatment to win approval from the Food and Drug Administration (in December 2024) is Kebilidi, a one-time gene therapy infused into the brain to treat a rare and devastating childhood disorder called aromatic L-amino acid decarboxylase deficiency.

"I think this is the dawn of something totally new," Gross said. "It is an incredibly exciting time to be doing this."

Explore more of the ways Rutgers research is shaping the future.

Robert Gross discusses the AMT-260 clinical trial, which is the only New Jersey trial site and among only 17 sites nationwide.