Antiviral Therapy

  • R. A. Smith
  • F. H. Norris
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 209)


Recently conventional viruses such as measles and rubella and unconventional infectious agents have been implicated as the cause of chronic, debilitating neurologic ailments’. This suggests that other nervous system diseases such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are likely to be due to a virus. In the case of ALS it has been thought that polio virus would be a logical etiologic candidate since both poliomyelitis and ALS share striking clinical similarities[2]. In both disorders the brunt of the pathologic process is primarily borne by the motor neuron. Further, some patients with poliomyelitis go on to develop weakness and wasting many years after their initial illness[3]. These reports have prompted epidemiologists to study the incidence of ALS in patients with a history of poliomyelitis. Poskanzer and his colleagues have reported an association between the two diseases[4]. Immunologic support for a relationship between ALS and polio rests on the finding that lymphocytes from ALS patients may be sensitized to polio antigen[5]. However, serum and CSF antibodies to polio are not disproportionately elevated in persons with ALS[6]. Although a number of attempts have been made to isolate a virus, including polio from ALS tissues, this has not been successful nor have attempts to transmit ALS to an animal host[7].


Multiple Sclerosis Amyotrophic Lateral Sclerosis Thymidine Kinase Amyotrophic Lateral Sclerosis Patient Viral Etiology 
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  1. 1.
    W. Meinke, R. A. Smith, W. D. Lancaster, D. A. Goldstein, and W. W. Tourtellote, Vitro labelled DNA for detection of viral genomes in multiple sclerosis: I. Papoviruses, Neurol., 27: 736–740 (1977).CrossRefGoogle Scholar
  2. 2.
    R. T. Johnson, Late progression of poliomyelitis: Discussion of pathogenesis, Rev.Infect.Pis., 6:(suppl.2)S568–S570 (1984).Google Scholar
  3. 3.
    M. C. Dalakas, et al., Late postpoliomyelitis muscular Atrophy: Clinical, virologic and immunologic studies, Rev.Infect.Pis., 6:(suppl.2)S562–S567 (1984).Google Scholar
  4. 4.
    P. C. Poskanzer, H. M. Cantor, and G. S. Kaplan, The frequency of preceding poliomyelitis in amyotrophic lateral sclerosis, in: “Motor Neuron Piseases: Research on Amyotrophic Lateral Sclerosis and Related Pisorders”, F. H. Norris, Jr. and L. T. Kurland, eds., Grune and Stratton, New York, 286–90 (1969).Google Scholar
  5. 5.
    E. Kott, E. Livni, and R. Zamir, et al., Cell mediated immunity to polio and HLA antigens in amyotrophic lateral sclerosis, Neurol., 29: 1040–1044 (1979).CrossRefGoogle Scholar
  6. 6.
    J. E. Kurent, B. R. Brooks, and P. L. Madden et al., CSF viral antibodies: Evaluation in amyotrophic lateral sclerosis and late-onset postpoliomyelitis progressive muscular atrophy, Arch.Neurol., 36: 269–273 (1979).PubMedCrossRefGoogle Scholar
  7. 7.
    N. E. Cremer, L. S. Oshiro, F. H. Norris, and E. H. Lennette, Cultures of Tissues from Patients with Amyotrophic Lateral Sclerosis, Arch. Neurol., 29: 331–333 (1973).Google Scholar
  8. 8.
    T. L. Munsat and W. G. Bradley, “Amyotrophic Lateral Sclerosis. Current Neurology”, Houghton Mifflin, Boston, pp. 3–27 (1979).Google Scholar
  9. 9.
    J. R. Miller, Prolonged intracerebral infection with poliovirus in asymptomatic mice, Ann.Neurol., 9: 590 - 596 (1981).PubMedCrossRefGoogle Scholar
  10. 10.
    H. L. Lipton, Theilerfs virus infection in mice: an unusual biphasic disease process leading to demyelination, Infect.Immun., 11: 1147–1155 (1975).PubMedGoogle Scholar
  11. 11.
    M. Chamorro, C. Aubert, and M. Brahic, Pemyelinating lesions due to Theiller’s virus are associated with ongoing central nervous system infection, J.Virol., 57: 992–996 (1986).PubMedGoogle Scholar
  12. 12.
    P. E. Kohne, C. J. Giws, L. White, S. M. Tracy, W. Meinke, and R. A. Smith, Virus detection by nucleic acid hybridization: examination of normal and ALS tissues for the presence of poliovirus, J.Gen. Virol., 56: 223–233 (1981).Google Scholar
  13. 13.
    M. Brahic, R. A. Smith, C. J. Gibbs, R. M. Garruto, W. W. Tourtellotte, and E. Cash, Petection of picronavirus sequences in nervous tissue of amyotrophic lateral sclerosis and control patients, Ann.Neurol., 18: 337–343 (1985).PubMedCrossRefGoogle Scholar
  14. 14.
    S. Van der Werf, F. Bregegere, H. Kopecka, N. Kitamura, P.G. Rothberg, P. Kourilsky, E. Wimmer, and M. Girard, Molecular cloning of the genome of poliovirus type 1 (recombinant PNA/colony filter hybridization/restriction endonucleases), Proc.Natl.Acad.Sci., USA, 78: 5983–5987.Google Scholar
  15. 15.
    A. C. Server and J. S. Wolinsky, “Approaches to Antiviral Therapy. Advances in Neurology”, L. Rowland, ed., Raven Press, 36:519–546 (1982).Google Scholar
  16. 16.
    J. A. Fyfe, P. M. Keller, P. A. Furman, R. L. Miller, and G. B. Elion, Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethooxymethyl) guanine, J.Biol. Chem., 253: 8721–8727 (1978).Google Scholar
  17. 17.
    M. S. Hirsh and M. N. Swartz, Prug Therapy: Antiviral agents, Medical Intelligence, 302: 949–953 (1980).Google Scholar
  18. 18.
    R. A. Smith, F. Norris, P. Palmer, L. Bernhardt, and R. J. Wills, Pistribution of alpha interferon in serum and cerebrospinal fluid after systemic administration, J.Clin.Pharmacol.Therap., 37: 85–88 (1985).CrossRefGoogle Scholar
  19. 19.
    R. Riccardi, R. J. Kramer, P. W. Trown, D. O’Neil, A. S. Levine, and D. G. Poplack, Serum and cerebrospinal fluid (CSF) pharmacokinetics of recombinant leukocyte A interferon (IFLrA) in monkeys, Proc. Amer.Assoc.Cancer Res. 23: 203 (1982).Google Scholar
  20. 20.
    R. A. Smith, D. Kingsbury, A. Alksne, H. James, and K. Cantell, Distribution of interferon in cerebrospinal fluid after systemic intrathecal and intraventricular administration, Ann.Neurol., 12: 81 (1982).Google Scholar
  21. 21.
    R. A. Smith, O. Abramsky, I. Steiner, H. Panitch, and K. Cantell, “The Experimental Treatment of Subacute Sclerosing Panencephalitis with Interferon. The Biology of the Interferon System”, W. E. Stewart and H. Schellekens, eds., Elsevier Science Publishers, pp. 505–510 (1986).Google Scholar
  22. 22.
    H. S. Panitch, J. Gomez, F. H. Norris, K. Cantell, and R. A. Smith, Remission of subacute sclerosing panencephalitis in patients treated with intraventricular interferon, Neurol, (in press).Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • R. A. Smith
    • 1
  • F. H. Norris
    • 2
  1. 1.Center for Neurologic StudySan DiegoUSA
  2. 2.Pacific Medical CenterSan FranciscoUSA

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