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New Epilepsy Treatments (2023): Neurostimulation, CBD, Gene Therapy for Seizures

Epilepsy affects over 50 million people worldwide, making it one of the most common neurological disorders globally.

For many living with epilepsy, achieving reliable seizure control remains a significant challenge, underscoring the need for continued innovation in treatment approaches.

Exciting new developments in the field are providing clinicians with an expanding array of therapeutic options to better manage this complex condition.

Key Facts:

  • Advances in neurostimulation devices offer new possibilities for reducing seizure frequency and severity in drug-resistant epilepsy. These include responsive neurostimulation (RNS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS).
  • Cannabidiol (CBD), a compound from the cannabis plant, has shown potential as an anticonvulsant and adjunctive therapy, especially for certain pediatric epilepsy syndromes.
  • Cutting-edge techniques like gene therapies and optogenetics allow researchers to elucidate the complex mechanisms underlying seizure activity, paving the way for more targeted treatments.
  • A combination of innovative therapies and personalized medicine approaches may provide the most effective seizure control and enhanced quality of life for individuals with epilepsy.

Source: Brain Sciences (2023)

Responsive Neurostimulation Systems Adapt to Epileptic Patients’ Brain Activity

For patients with epilepsy uncontrolled by medications, neurostimulation devices can provide an alternative treatment option.

Unlike medication taken on a regular schedule, neurostimulation acts in response to a patient’s brain activity patterns.

Responsive neurostimulation (RNS) is an example of a “closed-loop” system designed to detect signs of impending seizures and deliver targeted electrical stimulation to stop them.

RNS consists of a neurostimulator surgically implanted in the skull, along with one or two electrodes placed in the seizure-initiating region of the brain.

The electrodes monitor brain activity continuously, while algorithms detect subtle changes indicative of oncoming seizures.

When a seizure is detected, the neurostimulator provides brief electrical pulses to disrupt aberrant firing patterns.

Over time, RNS adapts its detection and stimulation parameters to the individual.

By responding on-demand rather than stimulating at set intervals, RNS aims to maximize seizure control while minimizing side effects.

Clinical studies have shown over 40% median seizure reduction at one year in drug-resistant epilepsy patients using RNS.

Long-term follow-up indicates sustained benefits, validating RNS as an effective option for suitable candidates.

Vagus Nerve Stimulation (VNS) for Seizures in Epilepsy

The vagus nerve is a critical channel of communication between the brain and internal organs.

Vagus nerve stimulation (VNS) leverages the vagus nerve’s connection to brain regions involved in seizures.

In this technique, a small electrical pulse generator is implanted under the skin in the chest.

Attached leads deliver mild stimulation to the left vagus nerve in the neck.

While not fully understood, VNS is thought to modulate brain networks toward increased inhibition, making seizures less likely.

By regularly stimulating the vagus nerve, VNS may help prevent seizure escalation and spread.

Clinical evidence demonstrates VNS efficacy as an adjunct treatment for refractory epilepsy, with many patients experiencing a 50% or greater reduction in seizure frequency.

Recent advances in VNS technology include closed-loop systems that automatically detect and stimulate in response to seizure activity, allowing more personalized treatment.

Rechargeable generators eliminate the need for frequent battery replacement surgeries.

Ongoing studies are exploring VNS benefits for other challenging epilepsy syndromes.

Deep Brain Stimulation (DBS) Targets Key Internal Structures

Deep brain stimulation (DBS) is a neurostimulation approach involving surgical implantation of electrodes that deliver electrical pulses to deep brain structures.

DBS directly targets regions implicated in seizures, such as the anterior nucleus of the thalamus.

Stimulation alters the excitability and synchronization of neural networks to prevent seizure propagation.

Rigorously controlled studies like the SANTE trial have demonstrated DBS efficacy in reducing seizures by over 40% in drug-resistant patients after one year.

Five-year follow-up data showed sustained improvements in seizure control and quality of life.

DBS may also be applied to alternative brain targets like the hippocampus or cerebellum in specific epilepsies.

While DBS can have risks including infection or hardware issues, clinically significant adverse effects are relatively uncommon.

This makes DBS a viable option for suitable drug-resistant epilepsy cases.

Advancements in imaging, electrode design, and stimulation programming will likely expand the possibilities of DBS therapy.

Cannabidiol (CBD): A Novel Plant-Based Approach

Cannabidiol (CBD) is a compound extracted from cannabis plants that has recently gained attention for its anticonvulsant properties.

In contrast to tetrahydrocannabinol (THC), CBD does not produce psychoactive effects but appears to modulate brain networks toward reduced excitability and enhanced inhibition.

The exact mechanisms are still under investigation but likely involve the endocannabinoid system and other receptors.

Following successful clinical trials, the CBD derivative Epidiolex was approved for treating severe childhood seizure disorders like Dravet and Lennox-Gastaut syndromes.

Real-world data indicate CBD may also benefit other refractory epilepsy patients who have not responded sufficiently to conventional anti-seizure medications.

Since interactions with other drugs are possible, clinicians must closely monitor usage.

As research continues, CBD stands out as a promising natural adjunctive therapy for drug-resistant epilepsies.

Gene Therapy to Target the Roots of Genetic Epilepsy

An exciting frontier in epilepsy treatment is gene therapy, which aims to correct genetic abnormalities underlying seizure disorders.

Using advanced gene editing techniques like CRISPR-Cas9, researchers can target specific mutations relevant to epileptogenesis with unprecedented precision.

Gene therapy has the potential to prevent seizures at their origin rather than just suppressing symptoms.

Animal studies have validated the concept of using gene therapy to reduce seizures, demonstrating safety and efficacy before human trials.

Early-phase human trials are underway, focusing on delivering therapeutic genes to the brain via engineered viral vectors.

While there are complex obstacles regarding delivery, efficacy, and safety to be addressed, gene therapy represents a revolutionary strategy for personalized treatment of genetic epilepsies.

Optogenetics Illuminates the Basis of Seizures

The emergence of optogenetics has revolutionized epilepsy research on a fundamental level.

This technique uses light to precisely control the activity of neurons genetically modified to express light-sensitive proteins called opsins.

By selectively activating or silencing specific cells, optogenetics provides unmatched insights into seizure dynamics.

Studies in animal models have identified “seizure hotspots” that initiate and propagate seizure activity.

Switching these regions on or off with optogenetics can bidirectionally trigger or prevent seizures, confirming their role as key nodes.

Researchers have also used optogenetics to parse the contributions of different cell types and circuits to hyperexcitability states.

While clinical applications are still distant, optogenetics discoveries help identify new targets for therapy development.

Its integration with closed-loop devices may someday enable on-demand light stimulation for preventing seizures.

The knowledge derived from optogenetics will be instrumental in designing smarter, more precise treatments for epilepsy.

Future Treatments for Epileptic Seizures: Combination & Precision

Given the heterogeneity of epilepsy, a one-size-fits-all approach to treatment is insufficient.

Combining cutting-edge therapies and customizing them to individual patients is likely the path to optimal seizure control.

For instance, combining neurostimulation with medications or other devices may have synergistic benefits.

Closed-loop systems personalized to a patient’s seizure patterns and biomarkers could optimize automated, adaptive treatments.

Leveraging big data and artificial intelligence can enable patient-tailored therapies.

Machine learning applied to EEG and genetic data may yield new insights and predictive models.

Such advances paired with innovative treatments could usher in a new era of precision medicine for epilepsy.

While challenges remain, the future of epilepsy treatment is brighter than ever thanks to remarkable ongoing advances.

Neurostimulation, cannabinoids, gene therapies and optogenetics are propelling the field rapidly toward more effective therapies and enhanced quality of life for the millions worldwide affected by uncontrolled seizures.

Continued innovation and personalized, combinatorial approaches promise to make drug-resistant epilepsy a thing of the past.

For patients and families who have struggled with uncontrolled seizures, the new wave of promising therapies inspires optimism and hope.


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