Wolfram syndrome is a rare multisystem autosomal recessive neurodegenerative disorder that affects the brain and central nervous system. Currently, there is no cure or treatment for Wolfram syndrome. Therefore, new techniques are needed to target the loss of the WFS1 gene. Gene therapy approach to introduce a functional gene using a viral or a non-viral vector could be a treatment strategy for Wolfram syndrome 1 (WS1). Viral vectors have therapeutic benefits and greater efficiency; however, they pose a high health risk. Recently pharmaceutical therapeutic research has developed cell-penetrating non-viral nano molecules that could be used as vectors for gene delivery. Among nonviral vectors, the unique properties of β-cyclodextrin suggest that it can be a promising safe vector for gene delivery.
Keywords: WFS1 gene; Wolfram syndrome; gene therapy; non-viral gene therapy; β-cyclodextrin.
Wolfram syndrome (WS) is a monogenic disorder where the dysfunction of one specific gene (WFS1 gene) results in many clinical manifestations such as diabetes mellites, diabetes insipidus, deafness and optic atrophy. Management of WS is primarily palliative that focuses on treating the individual symptoms that do not address the underlying genetic defect. Gene therapy is a novel treatment approach, where a functional gene is introduced using a viral or a non-viral vector to replace a non-functional gene, and it can be used as a treatment for WS. Genes are usually delivered via viral or non-viral vectors. However, viral vectors pose safety risks, and non-viral vectors are safe but pose limited efficiency. Therefore, evaluating non-viral vectors has the potential to shed light on the development of an effective and safe non-viral gene therapy vector for neurodegenerative diseases such as WS.