Genes of Growth Factors and Neurotrophins as Promising Therapeutic Transgenes for Gene and Cell Therapy of Neurodegenerative Diseases

Abstract Severe neurodegenerative disorders, including the most common Alzheimer’s disease (AD) and Parkinson’s disease (PD), are characterized by aggregation of pathological forms of proteins in the brain, nerve cells death, neuroinflammation, and an imbalance of growth factors and neurotrophins. The processes hinder natural regeneration of neural tissue and lead to brain atrophy and severe cognitive and motor impairments. Treating patients with neurodegenerative diseases remains a significant challenge in medicine. Existing drug therapy can slow down disease progression and improve symptoms in AD and PD, but does not stop the neurodegenerative processes in the brain or promote neural tissue regeneration. Gene-cell therapy provides a promising approach to treating such patients. This innovative approach is based on the ability of transduced cells and therapeutic proteins they express to influence the neurodegenerative processes that develop in AD and PD and stimulate neuroregeneration. Genes encoding the vascular endothelial growth factor (VEGF) and neurotrophic factors, such as the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), are of greatest interest as therapeutic transgenes for gene-cell therapy of AD and PD. The factors and their effect on neuroregeneration are the most studied. The review describes the specifics of AD and PD pathogenesis in experimental models and considers the clinical studies performed to assess the efficacy of transduced cells expressing VEGF, NGF, and BDNF in the treatment of AD and PD. Various viral vectors can be used for cell transduction; their advantages and disadvantages are discussed in the review. Based on the analysis of experimental and clinical trial results, the most promising drug is proposed for personalized treatment of AD and PD patients.