Growth Factors and Their Application in the Therapy of Hereditary Neurodegenerative Diseases

Abstract

Hereditary neurodegenerative diseases (hNDDs) such as Alzheimer's, Parkinson's, Huntington's disease, and others are primarily characterized by their progressive nature, severely compromising both the cognitive and motor abilities of patients. The underlying genetic component in hNDDs contributes to disease risk, creating a complex genetic landscape. Considering the fact that growth factors play crucial roles in regulating cellular processes, such as proliferation, differentiation, and survival, they could have therapeutic potential for hNDDs, provided appropriate dosing and safe delivery approaches are ensured. This article presents a detailed overview of growth factors, and explores their therapeutic potential in treating hNDDs, emphasizing their roles in neuronal survival, growth, and synaptic plasticity. However, challenges such as proper dosing, delivery methods, and patient variability can hinder their clinical application.

Keywords: BDNF; CNTF; FGF-2; GDNF; HGF; IGF-1; NGF; TGF-β1; VEGF; gene therapy; growth factors; hereditary neurodegenerative diseases.

Figure 1

This figure summarizes GF-based gene therapy approaches for hNDDs covered in this review. Purified Recombinant Protein: This approach involves obtaining and directly administering purified recombinant GFs (e.g., BDNF, GDNF, IGF-1, NGF, FGF-2, CNTF, and TGF-β1) to the target cells. Growth Factor-Releasing Genetically Modified Cells: involves the utilization of cells (e.g., mesenchymal stem cells, fibroblasts, bone marrow stromal cells, macrophages) genetically engineered to release GFs like BDNF, HGF, NGF, and GDNF. Delivery of Growth Factor Gene: This involves the delivery of genes encoding GFs directly to target areas using viral vectors (e.g., AAV and HSV) in order to enable the patient’s own cells to produce the necessary GFs, such as BDNF, GDNF, VEGF-A, and CNTF, providing a sustained therapeutic effect. Activation of the Expression of Growth Factor: Using pharmacological agents or small molecules to enhance the endogenous expression of GFs (e.g., CNTF and TGF-β1) within the target cells. Delivery of Growth Factor Mimetic: Employing mimetics, i.e., synthetic molecules designed to mimic the biological activity of natural GFs. These mimetics bind to and activate GF receptors, such as IGF-1 mimetics, providing neuroprotective effects similar to endogenous factors.