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

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2018 Jul 21

PMID 30027340

Citations 4

Authors

Huiying Gu

Yvonne Kirchhein

Timothy Zhu

Gang Zhao

Hongjun Peng

Eileen Du

Junyi Liu

James A Mastrianni

Martin R Farlow

Richard Dodel

Yansheng Du

Affiliations

Soon will be listed here.

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.

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References

Mabbott N, Williams A, Farquhar C, Pasparakis M, Kollias G, Bruce M . Tumor necrosis factor alpha-deficient, but not interleukin-6-deficient, mice resist peripheral infection with scrapie. J Virol. 2000; 74(7):3338-44. PMC: 111835. DOI: 10.1128/jvi.74.7.3338-3344.2000. View

Montrasio F, Frigg R, Glatzel M, Klein M, Mackay F, Aguzzi A . Impaired prion replication in spleens of mice lacking functional follicular dendritic cells. Science. 2000; 288(5469):1257-9. DOI: 10.1126/science.288.5469.1257. View

Bugiani O, Giaccone G, Piccardo P, Morbin M, Tagliavini F, Ghetti B . Neuropathology of Gerstmann-Sträussler-Scheinker disease. Microsc Res Tech. 2000; 50(1):10-5. DOI: 10.1002/1097-0029(20000701)50:1<10::AID-JEMT3>3.0.CO;2-6. View

Mabbott N, Mackay F, Minns F, Bruce M . Temporary inactivation of follicular dendritic cells delays neuroinvasion of scrapie. Nat Med. 2000; 6(7):719-20. DOI: 10.1038/77401. View

Bessos H, Drummond O, Prowse C, Turner M, MacGREGOR I . The release of prion protein from platelets during storage of apheresis platelets. Transfusion. 2001; 41(1):61-6. DOI: 10.1046/j.1537-2995.2001.41010061.x. View

Heppner F, Christ A, Klein M, Prinz M, Fried M, Kraehenbuhl J . Transepithelial prion transport by M cells. Nat Med. 2001; 7(9):976-7. DOI: 10.1038/nm0901-976. View

Du Y, Dodel R, Hampel H, Buerger K, Lin S, Eastwood B . Reduced levels of amyloid beta-peptide antibody in Alzheimer disease. Neurology. 2001; 57(5):801-5. DOI: 10.1212/wnl.57.5.801. View

Prinz M, Montrasio F, Klein M, Schwarz P, Priller J, Odermatt B . Lymph nodal prion replication and neuroinvasion in mice devoid of follicular dendritic cells. Proc Natl Acad Sci U S A. 2002; 99(2):919-24. PMC: 117406. DOI: 10.1073/pnas.022626399. View

Dodel R, Hampel H, Depboylu C, Lin S, Gao F, Schock S . Human antibodies against amyloid beta peptide: a potential treatment for Alzheimer's disease. Ann Neurol. 2002; 52(2):253-6. DOI: 10.1002/ana.10253. View

10.

White A, Enever P, Tayebi M, Mushens R, Linehan J, Brandner S . Monoclonal antibodies inhibit prion replication and delay the development of prion disease. Nature. 2003; 422(6927):80-3. DOI: 10.1038/nature01457. View

11.

Du Y, Wei X, Dodel R, Sommer N, Hampel H, Gao F . Human anti-beta-amyloid antibodies block beta-amyloid fibril formation and prevent beta-amyloid-induced neurotoxicity. Brain. 2003; 126(Pt 9):1935-9. DOI: 10.1093/brain/awg191. View

12.

Meiner Z, Halimi M, Polakiewicz R, Prusiner S, Gabizon R . Presence of prion protein in peripheral tissues of Libyan Jews with Creutzfeldt-Jakob disease. Neurology. 1992; 42(7):1355-60. DOI: 10.1212/wnl.42.7.1355. View

13.

Solforosi L, Criado J, McGavern D, Wirz S, Sanchez-Alavez M, Sugama S . Cross-linking cellular prion protein triggers neuronal apoptosis in vivo. Science. 2004; 303(5663):1514-6. DOI: 10.1126/science.1094273. View

14.

Aguzzi A, Sigurdson C . Antiprion immunotherapy: to suppress or to stimulate?. Nat Rev Immunol. 2004; 4(9):725-36. DOI: 10.1038/nri1437. View

15.

Daude N . Prion diseases and the spleen. Viral Immunol. 2004; 17(3):334-49. DOI: 10.1089/vim.2004.17.334. View

16.

Dodel R, Du Y, Depboylu C, Hampel H, Frolich L, Haag A . Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2004; 75(10):1472-4. PMC: 1738770. DOI: 10.1136/jnnp.2003.033399. View

17.

Park C, Choi Y . How do follicular dendritic cells interact intimately with B cells in the germinal centre?. Immunology. 2004; 114(1):2-10. PMC: 1782056. DOI: 10.1111/j.1365-2567.2004.02075.x. View

18.

Tan J, Ma Z, Han L, Du R, Zhao L, Wei X . Caffeic acid phenethyl ester possesses potent cardioprotective effects in a rabbit model of acute myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2005; 289(5):H2265-71. DOI: 10.1152/ajpheart.01106.2004. View

19.

Prusiner S . Molecular biology of prion diseases. Science. 1991; 252(5012):1515-22. DOI: 10.1126/science.1675487. View

20.

Aguzzi A, Heikenwalder M . Pathogenesis of prion diseases: current status and future outlook. Nat Rev Microbiol. 2006; 4(10):765-75. DOI: 10.1038/nrmicro1492. View