Systemic IGF-1 gene delivery by rAAV9 improves spontaneous autoimmune peripheral polyneuropathy (SAPP).

Abstract

Spontaneous autoimmune peripheral polyneuropathy (SAPP) is a mouse model of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in non-obese diabetic (NOD) mice null for costimulatory molecule, B7-2 gene (B7-2-/-). SAPP is a chronic progressive and multifocal inflammatory and demyelinating polyneuropathy of spontaneous onset with secondary axonal degeneration. Insulin-like growth factor 1(IGF-1) is a pleiotropic factor with neuroprotective, regenerative, and anti-inflammatory effects with extensive experience in its preclinical and clinical use. Systemic delivery of recombinant adeno-associated virus serotype 9 (rAAV9) provides robust and widespread gene transfer to central and peripheral nervous systems making it suitable for gene delivery in neurological diseases. A significant proportion of patients with inflammatory neuropathies like CIDP do not respond to current clinical therapies and there is a need for new treatments. In this study, we examined the efficacy IGF-1 gene therapy by systemic delivery with rAAV9 in SAPP model. The rAAV9 construct also contained a reporter gene to monitor the surrogate expression of IGF-1. We found significant improvement in neuropathic disease after systemic delivery of rAAV9/IGF-1 gene at presymptomatic and symptomatic stages of SAPP model. These findings support that IGF-1 treatment (including gene therapy) is a viable therapeutic option in immune neuropathies such as CIDP.

• Authors: Tong Gao, Nataliia Bogdanova, Sameera Ghauri, Gang Zhang, Jianxin Lin, Kazim Sheikh
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 5408 (04 03 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 29615658 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Recombinant
• Insulin-Like Growth Factor I

Topics

• Animals
• Asymptomatic Diseases
• DNA, Recombinant (genetics)
• Dependovirus (genetics)
• Disease Models, Animal
• Gene Transfer Techniques
• Genetic Therapy
• Insulin-Like Growth Factor I (genetics)
• Mice
• Peripheral Nerve Injuries (complications)
• Polyradiculoneuropathy, Chronic Inflammatory Demyelinating (complications, genetics, therapy)