Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases

Abstract

The etiology of many neurological diseases affecting the central nervous system (CNS) is unknown and still needs more effective and specific therapeutic approaches. Gene therapy has a promising future in treating neurodegenerative disorders by correcting the genetic defects or by therapeutic protein delivery and is now an attraction for neurologists to treat brain disorders, like Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, spinocerebellar ataxia, epilepsy, Huntington's disease, stroke, and spinal cord injury. Gene therapy allows the transgene induction, with a unique expression in cells' substrate. This article mainly focuses on the delivering modes of genetic materials in the CNS, which includes viral and non-viral vectors and their application in gene therapy. Despite the many clinical trials conducted so far, data have shown disappointing outcomes. The efforts done to improve outcomes, efficacy, and safety in the identification of targets in various neurological disorders are also discussed here. Adapting gene therapy as a new therapeutic approach for treating neurological disorders seems to be promising, with early detection and delivery of therapy before the neuron is lost, helping a lot the development of new therapeutic options to translate to the clinic.

Constitutive IL-1RA production by modified immune cells protects against IL-1–mediated inflammatory disorders

“…The gene therapy arena is rapidly expanding to include the delivery of soluble immunomodulatory proteins, including cytokines and growth and coagulation factors, which can overcome the poor stability and biodistribution of biological therapeutics ( 29 , 30 ). IL-1RA gene transfer strategies have mainly been tested in various forms of arthritis (rheumatoid arthritis and osteoarthritis).…”

Lipid-based nanoparticles and RNA as innovative neuro-therapeutics

“…Today, the treatment of brain malignancies such as glioblastoma or neurodegenerative diseases still remains an elusive ( Mullard, 2021 ; Sun and Roy, 2021 ). Gene therapy is a promising approach to developing new medicinal products for a plethora of different diseases ( Sudhakar and Richardson, 2019 ; Parambi et al, 2022 ). For instance, the small interfering RNAs can downregulate the expression of pathological proteins that are present in diseases.…”

Revealing the role of the benzyloxy pharmacophore in the design of a new class of monoamine oxidase‐B inhibitors

“…Several neurodegenerative illnesses are currently being diagnosed easily and have treatment for neurodegeneration, which is the gradual deterioration of a neuron's structure or activity which may lead to cell death. [3][4][5] Millions of people around the world suffer from neurodegenerative disorders.…”

“…[12,13] The active site of MAO-A consists of a single hydrophobic cavity to which the substrate binds whereas MAO-B consists of two different cavities, that is, a substrate cavity and a small entrance cavity. [3,14] The substrate cavity of the MAO-B isoform connects to the FAD cofactors, while the entrance cavity is localized to the outer portion of protein.…”

“…Several neurodegenerative illnesses are currently being diagnosed easily and have treatment for neurodegeneration, which is the gradual deterioration of a neuron's structure or activity which may lead to cell death. [ 3–5 ] Millions of people around the world suffer from neurodegenerative disorders. While therapies can alleviate some of the physical or mental complications associated with neurodegenerative diseases, there are currently no proven cures or methods to delay disease progression.…”