Gene Therapy, A Potential Therapeutic Tool for Neurological and Neuropsychiatric Disorders: Applications, Challenges and Future Perspective

Abstract

Neurological and neuropsychiatric disorders are the main risks for the health care system, exhibiting a huge socioeconomic load. The available range of pharmacotherapeutics mostly provides palliative consequences and fails to treat such conditions. The molecular etiology ofvarious neurological and neuropsychiatric disorders is mostly associated with a change in genetic background, which can be inherited/triggered by other environmental factors. To address such conditions, gene therapy is considered a potential approach claiming a permanent cure of the disease primarily by deletion, silencing, or edition of faulty genes and by insertion of healthier genes. In gene therapy, vectors (viral/non-vial) play an important role in delivering the desired gene to a specific region of the brain. Targeted gene therapy hasunraveled opportunitiesfor the treatment of many neurological and neuropsychiatric disorders. For improved gene delivery, the current techniques are mainly focusing on designing a precise viral vector, plasmid transfection, nanotechnology, microRNA, and in vivo clustered regulatory interspaced short palindromic repeats (CRISPR)-based therapy. These latest techniques have great benefits in treating predominant neurological and neurodevelopmental disorders, including Parkinson's disease, Alzheimer's disease, and autism spectrum disorder, as well as rarer diseases. Nevertheless, all these delivery methods have their limitations, including immunogenic reactions, off-target effects, and a deficiency of effective biomarkers to appreciate the effectiveness of therapy. In this review, we present a summary of the current methods in targeted gene delivery, followed by the limitations and future direction of gene therapy for the cure of neurological and neuropsychiatric disorders.

Landscape of NRXN1 Gene Variants in Phenotypic Manifestations of Autism Spectrum Disorder: A Systematic Review

“…One of the emerging approaches in treating genetic disorders involves gene editing [100][101][102]. This technique uses a biological system, such as CRISPR/Cas9, to precisely excise a specific gene segment and employ a biological vector to insert a desired sequence [103][104][105][106]. These treatments are ideal, as they are permanent, unlike the multimodal management that is currently being utilized [107].…”

Recent Updates on Corticosteroid-Induced Neuropsychiatric Disorders and Theranostic Advancements through Gene Editing Tools

“…The gene-editing approach in the gene therapy category has proved to be more promising than the other subsets. This approach can be utilized for various purposes such as gene regulation/repair, total dormancy of toxic genes, etc., though its onsite efficacy and site-specific deliveries are unsolved queries to date leading to its deferred clinical application [109]. In traditional approaches, the defective genes were reinstated with the rectified ones through the various vector types and induced the new gene sets inside the cells to elicit the production of appropriate functional proteins as mentioned in Table 1 [110].…”