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Breakthrough Research Offers Hope for Epilepsy Treatment

A collaborative research effort involving UC San Francisco, UC Santa Cruz, and UC Berkeley has unveiled a potential new approach to treating epilepsy by using light pulses to suppress seizure-like activity in brain neurons.

The study utilized brain tissue acquired from epilepsy patients undergoing surgical treatment, a unique resource that allowed researchers to study the patterns and triggers of seizures in real human cells.

The long-term goal of this innovative technique is to eliminate the need for invasive neurosurgery to excise the brain tissue where seizures initiate, thereby offering a more patient-friendly alternative for those who do not respond adequately to conventional medications.

Employing a cutting-edge method known as optogenetics, which employs a non-harmful virus to introduce light-sensitive genes into specific neurons, the researchers could activate or deactivate these cells using targeted light pulses.

This research marks the first successful demonstration of using optogenetics to modulate seizure activity in living human brain tissue, potentially paving the way for new therapies for a range of neurological disorders.

Subduing Epilepsy’s Spikes

To sustain the brain tissue for the duration of their experiments, which spanned several weeks, the researchers created an environment that closely resembled the conditions found within the human skull.

John Andrews, MD, a neurosurgery resident, carefully placed the tissue in a nutrient solution that mimicked the cerebrospinal fluid surrounding the brain. Meanwhile, David Schaffer, PhD, a biomolecular engineer at UC Berkeley, identified the optimal virus for delivering the light-sensitive genes to the neurons of interest.

The team arranged the tissue on a grid of electrodes capable of detecting the electrical signals exchanged among neurons. Under normal circumstances, brain neurons communicate at varying frequencies, yielding a steady electrical hum. However, during seizures, this activity can become synchronized, resulting in overwhelming bursts of electrical energy.

With the goal of preventing these disruptive bursts, the researchers aimed to inhibit the activity of neurons that had been genetically modified to express light-sensitive proteins.

Remote-Controlled Experimentation

Conducting their experiments without compromising the integrity of the brain tissue presented a challenge. The tiny electrodes were separated by just 17 microns, less than half the width of a human hair, meaning even minor movements could skew the results.

To address this, Mircea Teodorescu, PhD, an associate professor of electrical and computer engineering at UCSC, developed a remote-control system that allowed for recording the electrical activity of the neurons while delivering light pulses from a distance. This innovative software enabled researchers in Santa Cruz to control experiments taking place in Nowakowski’s San Francisco lab, thus avoiding the need for physical presence.

“This collaboration has been key to overcoming an incredibly complex research challenge,” Teodorescu remarked. “Our success demonstrates the power of combining the strengths of our institutions.”

New Insights into Seizures

The optogenetics methodology enabled the team to concentrate on specific neuron populations, allowing them to identify which types and quantities of neurons were instrumental in triggering seizures. They also determined the minimum intensity of light required to modulate the neurons’ electrical behavior within living brain slices.

Parallel investigations also illuminated how neuronal interactions serve to inhibit seizure activities. Edward Chang, MD, chair of Neurological Surgery at UCSF, expressed optimism about the implications of these findings for future epilepsy treatment.

“I envision a future where such approaches reduce or eliminate the need for invasive surgeries,” said Chang, who, along with Nowakowski, is affiliated with the UCSF Weill Institute for Neurosciences. “We could provide patients with a more nuanced and effective means to manage their seizures.”

Authors: The study features contributions from various researchers, including David Shinn, Albert Wang, Matthew Keefe, PhD, Kevin Donohue, Hanh Larson, Kurtis Auguste, MD, Vikaas Sohal, MD, PhD, and Cathryn Cadwell, MD, PhD from UCSF, alongside a diverse group of collaborators from UCSC and UC Berkeley.

Funding: The research received support from multiple institutions, including the National Institutes of Health, the National Science Foundation, Schmidt Futures Foundation, Weill Neurohub, the Esther A & Joseph Klingenstein Fund, the Shurl and Kay Curci Foundation, the Sontag Foundation, and a contribution from the William K. Bowes Jr Foundation.

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