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S3‐01–04: Prion vaccination
Author(s) -
Wisniewski Thomas
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.374
Subject(s) - titer , salmonella , immunization , vaccination , virology , immunology , immune system , biology , antibody , immunity , active immunization , toxicity , antibody titer , recombinant dna , medicine , bacteria , biochemistry , genetics , gene
classes of compounds showed any beneficial effect in in vivo and/or in vitro models. Studies from our group led to recognize that tetracyclines are able to (i) revert the protease-resistance of the disease-associated prion protein isoforms extracted from brain tissue of patients with all forms of Creutzfeldt-Jakob disease (CJD) and cattle with BSE, (ii) reduce the infectivity titer in prion-contaminated material, and (iii) prolong survival of prion-infected animals. Methods: Twenty-one patients fulfilling the diagnostic criteria of probable CJD were authorized to receive compassionate treatment with doxycycline at a daily oral dose of 100 mg, from the time of diagnosis to death. Survival times were compared with those of 78 probable CJD patients who did not receive doxycycline treatment. Results: The prolonged treatment with doxycycline was well tolerated in all patients, without adverse secondary effects. The subjects treated with doxycycline (n 21) survived significantly longer than untreated patients (n 78); in particular, the survival time (median SE) was 13.0 4.0 months in the former and 6.0 0.7 months in the latter (Log Rank test: p 0.001). A significant difference was still present when the doxycyclinetreated group was compared to an untreated group equivalent for sex, age at onset and codon 129 PRNP polymorphism (treated: 13.9 3.8 months, untreated: 6.1 0.5 months, p 0.01), which are major predictors of survival in CJD. Conclusions: The positive effects of doxycycline treatment on CJD survival seen in this observational study are currently under verification in a randomized, double-blind study of doxycycline versus placebo, approved by the Italian Agency of Drug. A positive outcome of this trial would activate similar studies in other neurodegenerative disorders due to protein misfolding such as Alzheimer’s disease, since the effects of doxycycline seem to be dependent upon a direct interaction with abnormal protein conformers having an extensive beta-sheet conformation rather than a specific amino acid sequence.