Skip to main content
SpringerLink
Log in

Experimental drug treatment of scrapie: A pathogenetic basis for rationale therapeutics

  • Published:
European Journal of Epidemiology Aims and scope Submit manuscript

Abstract

Pharmacological treatment with polyanions or amphotericin B in hamsters with experimental scrapie reveals that it is possible to delay the appearance of the disease only when the drug is given before the invasion of the agent into the clinical target areas of the brain. We suggest such early treatment may be possible for individuals at high risk of acquiring the disease, such as healthy mutation-positive relatives of patients with familial Creutzfeldt-Jakob disease or Gerstmann-Sträussler syndrome, or recipients of potentially contaminated pituitary-extracted human growth hormone.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Billette de VillemeurT., BeauvaisP., GourmelenM. and RichardetJ.M. (1991): Creutzfeldt-Jakob disease in children treated with growth hormone. - Lancet, 337: 864–865.

    Google Scholar 

  2. BrownP. (1990): A therapeutic panorama of the spongiform encephalopathies. - Antiv. Chem. Chemother. 1: 75–83.

    Google Scholar 

  3. BrownP. (1990): Transmissible spongiform encephalopathies in humans: kuru, Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease. - Can. J. Vet. Res. 54: 38–41.

    Google Scholar 

  4. BrownP., GajdusekD.C., GibbsC.J.Jr. and AsherD.M. (1985): Potential epidemic of Creutzfeldt-Jakob disease from human growth hormone therapy. - N. Engl. J. Med. 313: 728–731.

    Google Scholar 

  5. BrownP., GoldfarbL.G. and GajdusekD.C. (1991): The new biology of spongiform encephalopathy: infectious amyloidoses with a genetic twist. - Lancet 337: 1019–1022.

    Google Scholar 

  6. BuchananC.R., PreeceM.A. and MilnerR.D.G. (1991): Mortality, neoplasia, and Creutzfeldt-Jakob disease in patients treated with human pituitary growth hormone in the United Kingdom. - Br. Med. J. 302: 824–828.

    Google Scholar 

  7. BruceM. and DickinsonA.G. (1987): Biological evidence that scrapie agent has an independent genoma. - J. Gen. Virol. 68: 79–89.

    Google Scholar 

  8. CasacciaP., LadoganaA., XiY.G. and PocchiariM. (1989): Levels of infectivity in the blood through the incubation period of hamsters peripherally injected with scrapie. - Arch. Virol. 108: 145–149.

    Google Scholar 

  9. DickinsonA.G. (1976): Scrapie in sheep and goats In:Slow Virus Diseases of Animal and Man. R.H. Kimberlin. Ed., North Holland, Amsterdam, pp. 209–241.

    Google Scholar 

  10. DickinsonA.G. and FraserH. (1972): Scrapie: effect of Dh gene on incubation period of extraneurally injected agent. - Heredity 29: 91–93.

    Google Scholar 

  11. DickinsonA.G., MeikleY.M.H. and FraserH. (1968): Identification of a gene which controls the incubation periods of some strains of scrapie in mice.- J. Comp. Pathol. 78: 293–299.

    Google Scholar 

  12. DickinsonA.G. and OutramG.W. (1988): Genetic aspects of unconventional virus infections: the basis of the virino hypothesis. In: Novel Infectious Agents and the Central Nervous System, G. Bock and J. Marsh. Eds., John Wiley & Sons, Ciba Foundation Symposium No. 135, Chichester, pp. 63–77.

    Google Scholar 

  13. DiringerH. (1984): Sustained viremia in experimental hamster scrapie. - Arch. Virol. 82: 105–109.

    Google Scholar 

  14. DiringerH. and EhlersB. (1991): Chemoprophylaxis of scrapie in mice. - J. Gen. Virol. 72: 457–460.

    Google Scholar 

  15. EhlersB. and DiringerH. (1984): Dextran sulphate 500 delays and prevents mouse scrapie by impairment of agent replication in spleen. - J. Gen. Virol. 65: 1325–1330.

    Google Scholar 

  16. EhlersB., RudolphR. and DiringerH. (1984): The reticuloendothelial system in scrapie pathogenesis. -J. Gen. Virol. 65: 423–428.

    Google Scholar 

  17. FarquharC.F. and DickinsonA.G. (1986): Prolongation of scrapie incubation period by an injection of dextran sulphate 500 within the month before or after infection. - J. Gen. Virol. 67: 463–473.

    Google Scholar 

  18. FradkinJ.E., SchonbergL.B., MillsJ.L., GunnW.J., PiperJ.M., WysowskiD.K., ThomsonR., DurakoS. and BrownP. (1991): Creutzfeldt-Jakob disease in pituitary growth hormone recipients in the United States. - JAMA 265: 880–884.

    Google Scholar 

  19. FraserH. (1976): The pathology of natural and experimental scrapie. In: Slow Virus Diseases of Animal and Man. R.H. Kimberlin. Ed., North Holland, Amsterdam, pp. 267–305.

    Google Scholar 

  20. FraserH. and DickinsonA.G. (1970): Pathogenesis of scrapie in the mouse: the role of the spleen. Nature 226: 462–463.

    Google Scholar 

  21. FraserH. and DickinsonA.G. (1978): Studies of the lymphoreticular systems in the pathogenesis of scrapie: the role of spleen and thymus. - J. Comp. Pathol. 88: 563–573.

    Google Scholar 

  22. HadlowW.J., KennedyR.C. and RaceR.E. (1982): Natural infection of Suffolk sheep with scrapie virus.- J. Infect. Dis. 146: 657–664.

    Google Scholar 

  23. HadlowW.J., KennedyR.C., RaceR.E. and EklundC.M. (1980): Virologic and neurohistologic findings in dairy goats affected with natural scrapie. - Vet. Pathol. 17: 187–199.

    Google Scholar 

  24. HourriganJ.L., KlingspornA.L., ClarkW. W. and DeCampM.G. (1979): Epidemiology of scrapie in the United States. In: Slow Transmissible Diseases of the Nervous System. S.B. Prusiner and W.J. Hadlow. Eds., - Academic Press, New York, vol. 1, pp. 331–356.

    Google Scholar 

  25. KimberlinR.H., ColeS. and WalkerC.A. (1987): Pathogenesis of scrapie is faster when infection is intraspinal instead of intracerebral. - Microb. Pathogen. 2: 405–415.

    Google Scholar 

  26. KimberlinR.H. and WalkerC.A. (1977): Characteristics of a short incubation model of scrapie in the golden hamster. - J. Gen. Virol. 34: 295–304.

    Google Scholar 

  27. KimberlinR.H. and WalkerC.A. (1978): Pathogenesis of mouse scrapie: effect of route of inoculation on infectivity titres and dose-response curves. - J. Comp. Pathol. 88: 39–47.

    Google Scholar 

  28. KimberlinR.H. and WalkerC.A. (1983): Invasion of the CNS by scrapie agent and its spread to different parts of the brain. In: Virus non Conventionnels et Affections du Systeme Nerveux Central. L.A. Court and F. Cathala Eds., Masson, Paris, pp. 17–23.

    Google Scholar 

  29. KimberlinR.H. and WalkerC.A. (1983): The antiviral compound HPA-23 can prevent scrapie when administered at the time of infection. - Arch. Virol. 78: 9–18.

    Google Scholar 

  30. KimberlinR.H. and WalkerC.A. (1986): Suppression of scrapie infection in mice by heteropolyanion 23, dextran sulfate, and some other polyanions. -Antimicrob. Agents Chemother. 30: 409–413.

    Google Scholar 

  31. KimberlinR.H. and WalkerC.A. (1986): Pathogenesis of scrapie (strain 263K) in hamsters infected intracerebrally, intraperitoneally or intraocularly. J. Gen. Virol. 67: 255–263.

    Google Scholar 

  32. KimberlinR.H. and WalkerC.A. (1988): Pathogenesis of experimental scrapie. In: Novel Infectious Agents and the Central Nervous System, G. Bock and J. Marsh. Eds., John Wiley & Sons, Ciba Foundation Symposium No. 135, Chichester, pp. 37–54.

    Google Scholar 

  33. Ladogana A., Casaccia P., Ingrosso L., Cibati M., Salvatore M., Xi Y.G., Masullo C. and Pocchiari M.: Sulphate polyanions prolong the incubation period of scrapie-infected hamster. - J. Gen. Virol., submitted.

  34. PocchiariM., SchmittingerS. and MasulloC. (1987): Amphotericin B delays the incubation period of scrapie in intracerebrally inoculated hamsters. - J. Gen. Virol. 68: 219–223.

    Google Scholar 

  35. PocchiariM., CasacciaP. and LadoganaA. (1989): Amphotericin B: a novel class of antiscrapie drugs. -J. Infect. Dis. 160: 795–802.

    Google Scholar 

  36. PocchiariM., MacchiG., PeanoS. and ConzA. (1988): Can potential hazard of Creutzfeldt-Jakob disease infectivity be reduced in the production of human growth hormone? Inactivation experiments with the 263K strain of scrapie. - Arch. Virol. 98: 131–135.

    Google Scholar 

  37. Pocchiari M., Peano S., Conz A., Eshkol A., Maillard F., Brown P., Gibbs CJ. Jr., Tenham-Fisher E. and Macchi G. (1991): Combination ultrafiltration and 6 M ureatreatment of human growth hormone effectively minimizes risk from potential Creutzfeldt-Jakob disease virus contamination. - Horm. Res., in press.

  38. WilesmithJ. W., WellsG.A.H., CranwellM.P. and RyanJ.B.M. (1988): Bovine spongiform encephalopathy: epidemiological studies. - Vet. Rec. 123: 638–644.

    Google Scholar 

Download references

Author information

Author notes

  1. M. Pocchiari

    Present address: Istituto di Patologia Generale, Università Cattolica del S. Cuore, Largo F. Vito, 1 - 00168, Roma, Italy

Authors and Affiliations

  1. Department of Biology, University of Lecce, Lecce

    M. Pocchiari

  2. Institute of General Pathology, Catholic University, Rome, Italy

    M. Salvatore, A. Ladogana, L. Ingrosso, Y. G. XI & M. Cibati

  3. Institute of Neurology, Catholic University, Rome, Italy

    C. Masullo

Authors
  1. M. Pocchiari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Salvatore
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Ladogana
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Ingrosso
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y. G. XI
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Cibati
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C. Masullo
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Corresponding author

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pocchiari, M., Salvatore, M., Ladogana, A. et al. Experimental drug treatment of scrapie: A pathogenetic basis for rationale therapeutics. Eur J Epidemiol 7, 556–561 (1991). https://doi.org/10.1007/BF00143139

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00143139

Key words

Search

Navigation