Gene therapy for neurodegenerative disorders: advances, insights and prospects

Abstract

Gene therapy is rapidly emerging as a powerful therapeutic strategy for a wide range of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Some early clinical trials have failed to achieve satisfactory therapeutic effects. Efforts to enhance effectiveness are now concentrating on three major fields: identification of new vectors, novel therapeutic targets, and reliable of delivery routes for transgenes. These approaches are being assessed closely in preclinical and clinical trials, which may ultimately provide powerful treatments for patients. Here, we discuss advances and challenges of gene therapy for neurodegenerative disorders, highlighting promising technologies, targets, and future prospects.

Future Prospects of Gene Therapy for Friedreich’s Ataxia

“…In the last decades, gene therapy has been consolidated as a promising treatment to many genetic disorders, such as spinal muscular atrophy (SMA) or Leber’s congenital amaurosis, with some gene therapy drugs already approved [ 23 , 24 ]. Other diseases with numerous preclinical and clinical studies are also being conducted, including, among others, Alzheimer’s disease, Amyotrophic lateral sclerosis (ALS), or Huntington’s disease [ 25 , 26 , 27 , 28 ]. This approach is based on the delivery of nucleic acids to patients in order to reverse or prevent their pathological phenotypes.…”

“…Therefore, in vivo gene therapy seems to be the best strategy. In this context, AAV is the most promising vector and the vast majority of gene therapy clinical trials for neurodegenerative diseases use AAVs [ 28 ]. Furthermore, gene therapies using these viral vectors have already been approved by the U.S. Food and Drug Administration (FDA).…”

On the Right Track to Treat Movement Disorders: Promising Therapeutic Approaches for Parkinson’s and Huntington’s Disease

“…For a more in-depth knowledge of gene therapy delivery systems and other cellular targets, reviews are published elsewhere (Sudhakar and Richardson, 2019;Chen et al, 2020).…”

“…Nowadays, there are several gene silencing/editing technologies, including RNA interference (RNAi), antisense oligonucleotides (ASO), and clustered interspaced short palindromic repeats (CRISPR/cas9), which can be used as therapies for the treatment of PD and HD. For a more in-depth knowledge of gene therapy delivery systems and other cellular targets, reviews are published elsewhere (Sudhakar and Richardson, 2019 ; Chen et al, 2020 ).…”

Gene Therapy in Movement Disorders: A Systematic Review of Ongoing and Completed Clinical Trials

“…Gene therapy is a rapidly evolving technology aiming to modulate the expression of one or more genes to achieve a clinical therapeutic benefit ( 1 ). Several gene therapy studies have now been conducted in movement disorders and other areas of neurology to target the pathogenesis of diseases, enhance the production of key enzymes involved in neurotransmitter metabolic pathways, or support the survival of specific cell populations.…”