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

Sci Rep. 2018 Apr 3;8(1):5408. doi: 10.1038/s41598-018-23607-9.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / genetics*
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / therapy*

Substances

  • DNA, Recombinant
  • Insulin-Like Growth Factor I