Adeno-Associated Viral Vectors in the Treatment of Epilepsy

Abstract

Epilepsy is a brain disorder characterized by a persistent predisposition to epileptic seizures. With various etiologies of epilepsy, a significant proportion of patients develop pharmacoresistance to antiepileptic drugs, which necessitates the search for new therapeutic methods, in particular, using gene therapy. This review discusses the use of adeno-associated viral (AAV) vectors in gene therapy for epilepsy, emphasizing their advantages, such as high efficiency of neuronal tissue transduction and low immunogenicity/cytotoxicity. AAV vectors provide the possibility of personalized therapy due to the diversity of serotypes and genomic constructs, which allows for increasing the specificity and effectiveness of treatment. Promising orientations include the modulation of the expression of neuropeptides, ion channels, transcription, and neurotrophic factors, as well as the use of antisense oligonucleotides to regulate seizure activity, which can reduce the severity of epileptic disorders. This review summarizes the current advances in the use of AAV vectors for the treatment of epilepsy of various etiologies, demonstrating the significant potential of AAV vectors for the development of personalized and more effective approaches to reducing seizure activity and improving patient prognosis.

Keywords: adeno-associated virus; antisense oligonucleotides; epilepsy; gene therapy; ion channels; neuropeptides; neurotrophic factors; receptors; transcription factors.

Figure 1

Components of the effective use of AAV vectors in the treatment of CNS disorders.

Figure 2

Experimental design for evaluating the efficacy of AAV vectors (serotypes 1, 2 and 8) carrying neuropeptide Y (NPY) and its receptor Y2 in two different transgene orders (NPY/Y2 or Y2/NPY); empty viral cassettes were used as a control. Wistar male rats were injected bilaterally with the viral vectors, followed by subcutaneous kainate injection to induce seizures. Key measurements included latency to the first motor seizure, time spent in motor seizure and latency to status epilepticus. Results from these measurements were used to assess the seizure-suppressant efficacy of the AAV vectors compared to an empty cassette control vector.