Overview[edit]

Epilepsy refers to a group of chronic neurological disorders that are characterized by seizures, affecting over 50 million people, or 0.4–1% of the global population.[3][4] There is a basic understanding of the pathophysiology of epilepsy, especially of forms characterized by the onset of seizures from a specific area of the brain (partial-onset epilepsy). Although most patients respond to medication, approximately 20%–30% do not improve with or fail to tolerate antiepileptic drugs.[5][6] For such patients, surgery to remove the epileptogenic zone can be offered in a small minority, but is not feasible if the seizures arise from brain areas that are essential for language, vision, movement or other functions. As a result, many people with epilepsy are left without any treatment options to consider, and thus there is a strong need for the development of innovative methods for treating epilepsy.


Through the use of viral vector gene transfer, with the purpose of delivering DNA or RNA to the epileptogenic zone, several neuropeptides, ion channels and neurotransmitter receptors have shown potential as transgenes for epilepsy treatment. Among vectors are adenovirus and adeno-associated virus vectors (AAV), which have the properties of high and efficient transduction, ease of production in high volumes, a wide range of hosts, and extended gene expression.[7] Lentiviral vectors have also shown promise.

Clinical research[edit]

Among challenges to clinical translation of gene therapy are possible immune responses to the viral vectors and transgenes and the possibility of insertional mutagenesis, which can be detrimental to patient safety.[8] Scaling up from the volume needed for animal trials to that needed for effective human transfection is an area of difficulty, although it has been overcome in other diseases. With its size of less than 20 nm, AAV in part addresses these problems, allowing for its passage through the extracellular space, leading to widespread transfection. Although lentivectors can integrate in the genome of the host this may not represent a risk for treatment of neurological diseases because adult neurons do not divide and so are less prone to insertional mutagenesis

Non-viral approaches[edit]

Magnetofection is done through the use of super paramagnetic iron oxide nanoparticles coated with polyethylenimine. Iron oxide nanoparticles are ideal for biomedical applications in the body due to their biodegradable, cationic, non-toxic, and FDA-approved nature. Under gene transfer conditions, the receptors of interest are coated with the nanoparticles. The receptors will then home in and travel to the target of interest. Once the particle docks, the DNA is delivered to the cell via pinocytosis or endocytosis. Upon delivery, the temperature is increased ever so slightly, lysing the iron oxide nanoparticle and releasing the DNA. Overall, the technique is useful for combatting slow vector accumulation and low vector concentration at target areas. The technique is also customizable to the physical and biochemical properties of the receptors by modifying the characteristics of the iron oxide nanoparticles.[26][27]

Future implications[edit]

The use of gene therapy in treating neurological disorders such as epilepsy has presented itself as an increasingly viable area of ongoing research with the primary targets being somatostatin, galanin, neuropeptide y, potassium channels, optogenetics and chemogenetics for epilepsy. As the field of gene therapy continues to grow and show promising results for the treatment of epilepsy among other diseases, additional research needs to be done in ensuring patient safety, developing alternative methods for DNA delivery, and finding feasible methods for scaling up delivery volumes.[28][29]