HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Stewart, L. A. Articles by Knight, R. S.G. Search for Related Content PubMed PubMed Citation Articles by Stewart, L. A. Articles by Knight, R. S.G. Related Collections Prion Clinical trials Systematic review/meta analysis Prion disease; see Infections/prion

Systematic review of therapeutic interventions in human prion disease

From Centre MRC Clinical Trials Unit (L.A.S.), London; MRC Clinical Trials Unit (L.H.M.R.), London; National Prion Clinic (G.F.K.), London; and National CJD Surveillance Unit (R.S.G.K.), Edinburgh, UK.

Address correspondence and reprint requests to Professor Lesley Stewart, Director, Centre for Reviews and Dissemination, University of York, York YO10 5DD UK ls536{at}york.ac.uk

Background: The potential threat of a large outbreak of variant Creutzfeldt-Jakob disease initiated a proliferation of research into the understanding and treatment of human prion disease. However, clinical research is at an early stage with a pressing need for objective evaluation of treatments to inform the design of future studies.

Methods: We aimed to summarize existing research on outcomes of patients with prion disease, considering any published clinical study and patient series with data on disease progression. Methods were prespecified in a protocol and studies were identified from systematic searches of multiple sources.

Results: One randomized trial was identified. Many studies were flawed or poorly reported, and therefore interpreted cautiously. One hundred forty published patient series revealed wide ranges in disease duration for each of the prion diseases. Thirty-three studies described the use of 14 drugs, 10 which were reported in single studies of three or fewer patients and one which was reported for two individual cases. Effects of four drugs were examined in more detail, with mixed results. The only current reliable evidence is from the single randomized trial suggesting that flupirtine may slow cognitive decline. Based on published information identified by this review, survival of most treated patients is within the ranges reported in the untreated patient series.

Conclusions: Thirty years of clinical investigation of patients with prion disease has resulted in little progress in either defining or evaluating potential treatments. Disease course and treatment of all patients must be evaluated within a structured framework, preferably within randomized controlled trials.

Abbreviations: ADAS-cog = Alzheimer’s Disease Assessment Scale–Cognitive Subscale; BSE = bovine spongiform encephalopathy; DD = duration of disease; GI = gastrointestinal; iCJD = iatrogenic CJD; iPD = inherited prion disease; PPS = pentosan polysulfate; RCT = randomized controlled trial; sCJD = sporadic Creutzfeldt-Jakob disease; vCJD = variant Creutzfeldt-Jakob disease.

Supplemental data at www.neurology.org

Disclosure: Lesley Stewart and Larysa Rydzewska have no competing interests to declare. Geraldine Keogh was a trial manager on the MRC Prion-1 trial during the preparation of this review; Richard Knight is Director of the National CJD Surveillance Unit in Edinburgh.

Received May 18, 2007. Accepted in final form September 14, 2007.