IVIG Delays Onset in a Mouse Model of Gerstmann-Sträussler-Scheinker Disease

Huiying Gu, Yvonne Kirchhein, Timothy Zhu, Gang Zhao, Hongjun Peng, Eileen Du, Junyi Liu, James A. Mastrianni, Martin R. Farlow, Richard Dodel, Yansheng Du

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Abstract

Our previous studies showed that intravenous immunoglobulin (IVIG) contained anti-Aβ autoantibodies that might be able to treat Alzheimer’s disease (AD). Recently, we identified and characterized naturally occurring autoantibodies against PrP from IVIG. Although autoantibodies in IVIG blocked PrP fibril formation and PrP neurotoxicity in vitro, it remained unknown whether IVIG could reduce amyloid plaque pathology in vivo and be used to effectively treat animals with prion diseases. In this study, we used Gerstmann-Sträussler-Scheinker (GSS)-Tg (PrP-A116V) transgenic mice to test IVIG efficacy since amyloid plaque formation played an important role in GSS pathogenesis. Here, we provided strong evidence that demonstrates how IVIG could significantly delay disease onset, elongate survival, and improve clinical phenotype in Tg (PrP-A116V) mice. Additionally, in treated animals, IVIG could markedly inhibit PrP amyloid plaque formation and attenuate neuronal apoptosis at the age of 120 days in mice. Our results indicate that IVIG may be a potential, effective therapeutic treatment for GSS and other prion diseases.

Original languageEnglish (US)
Pages (from-to)2353-2361
Number of pages9
JournalMolecular Neurobiology
Volume56
Issue number4
DOIs
StatePublished - Apr 1 2019

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Keywords

  • Amyloid plaque
  • Apoptosis
  • IVIG
  • Prion

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Gu, H., Kirchhein, Y., Zhu, T., Zhao, G., Peng, H., Du, E., Liu, J., Mastrianni, J. A., Farlow, M. R., Dodel, R., & Du, Y. (2019). IVIG Delays Onset in a Mouse Model of Gerstmann-Sträussler-Scheinker Disease. Molecular Neurobiology, 56(4), 2353-2361. https://doi.org/10.1007/s12035-018-1228-0