Original Article
Prions in the Urine of Patients with Variant Creutzfeldt–Jakob
Disease
Fabio Moda, Ph.D., Pierluigi Gambetti, M.D., Silvio Notari, Ph.D., Luis
Concha-Marambio, B.Sc., Marcella Catania, Ph.D., Kyung-Won Park, Ph.D., Emanuela
Maderna, B.Sc., Silvia Suardi, B.Sc., Stéphane Haïk, M.D., Ph.D., Jean-Philippe
Brandel, M.D., James Ironside, M.D., Richard Knight, M.D., Fabrizio Tagliavini,
M.D., and Claudio Soto, Ph.D.
N Engl J Med 2014; 371:530-539August 7, 2014DOI: 10.1056/NEJMoa1404401
Background
Prions, the infectious agents responsible for transmissible spongiform
encephalopathies, consist mainly of the misfolded prion protein (PrPSc). The
unique mechanism of transmission and the appearance of a variant form of
Creutzfeldt–Jakob disease, which has been linked to consumption of
prion-contaminated cattle meat, have raised concerns about public health.
Evidence suggests that variant Creutzfeldt–Jakob disease prions circulate in
body fluids from people in whom the disease is silently incubating.
Methods
To investigate whether PrPSc can be detected in the urine of patients with
variant Creutzfeldt–Jakob disease, we used the protein misfolding cyclic
amplification (PMCA) technique to amplify minute quantities of PrPSc, enabling
highly sensitive detection of the protein. We analyzed urine samples from
several patients with various transmissible spongiform encephalopathies (variant
and sporadic Creutzfeldt–Jakob disease and genetic forms of prion disease),
patients with other degenerative or nondegenerative neurologic disorders, and
healthy persons.
Results
PrPSc was detectable only in the urine of patients with variant
Creutzfeldt–Jakob disease and had the typical electrophoretic profile associated
with this disease. PrPSc was detected in 13 of 14 urine samples obtained from
patients with variant Creutzfeldt–Jakob disease and in none of the 224 urine
samples obtained from patients with other neurologic diseases and from healthy
controls, resulting in an estimated sensitivity of 92.9% (95% confidence
interval [CI], 66.1 to 99.8) and a specificity of 100.0% (95% CI, 98.4 to
100.0). The PrPSc concentration in urine calculated by means of quantitative
PMCA was estimated at 1×10−16 g per milliliter, or 3×10−21 mol per milliliter,
which extrapolates to approximately 40 to 100 oligomeric particles of PrPSc per
milliliter of urine.
Conclusions
Urine samples obtained from patients with variant Creutzfeldt–Jakob disease
contained minute quantities of PrPSc. (Funded by the National Institutes of
Health and others.)
The views expressed in this article are those of the authors and not
necessarily those of the U.K. Department of Health.
Supported by grants from the National Institutes of Health (P01AI077774,
R42NS079060, R01NS049173, and R01NS078745, to Dr. Soto), PrioNet Canada and
Merck Serono (to Dr. Soto), the Italian Ministry of Health, Associazione
Italiana Encefalopatie da Prioni, and Ministero dell'Università e della Ricerca
(RBAP11FRE9, to Dr. Tagliavini), the Charles S. Britton Fund (P01AG14359, to Dr.
Gambetti), and the U.K. Department of Health and the Scottish Government (to
Drs. Ironside and Knight).
Disclosure forms provided by the authors are available with the full text
of this article at NEJM.org.
We thank Suzanne Lowrie, F.I.B.M.S., for assistance in collecting urine
samples, Denisse Gonzalez-Romero, M.Sc., of the University of Texas Medical
School at Houston for technical assistance, and Dr. Glenn Telling of Colorado
State University for providing colonies of transgenic mice expressing human
prion protein.
Source Information
From the Mitchell Center for Research in Alzheimer's Disease and Related
Brain Disorders, University of Texas Medical School at Houston, Houston (F.M.,
L.C.-M., K.-W.P., C.S.); Foundation Carlo Besta Neurologic Institute, Milan
(F.M., M.C., E.M., S.S., F.T.); National Prion Disease Pathology Surveillance
Center, Case Western Reserve University, Cleveland (P.G., S.N.); Universidad de
los Andes, Facultad de Medicina, Santiago, Chile (L.C.-M.); Assistance
Publique–Hôpitaux de Paris, Cellule Nationale de Référence des Maladies de
Creutzfeldt–Jakob, Groupe Hospitalier Pitié–Salpêtrière, INSERM Unité 1127,
Université Pierre et Marie Curie–Paris 6, and Centre Nationale de la Recherche
Scientifique, Unité Mixte de Recherche — all in Paris (S.H., J.-P.B.); and the
National CJD Research and Surveillance Unit, Western General Hospital,
University of Edinburgh, Edinburgh (J.I., R.K.).
Address reprint requests to Dr. Soto at the University of Texas Medical
School at Houston, 6431 Fannin St., Houston, TX77030, or at
claudio.soto@uth.tmc.edu.
http://www.nejm.org/doi/full/10.1056/NEJMoa1404401?query=featured_home
1996 NARANG URINE TEST
5.289 We have concluded, for the reasons given above, that Dr Narang's work
received fair consideration by MAFF scientists. While we would pay tribute to Dr
Narang's dedication to research into TSEs, we feel that he had a fair
opportunity to demonstrate the validity of his work but did not succeed in doing
so.
8. I was in receipt of no extra funds beyond those provided by the NHS and
the University of London to run my laboratories and pay my salary as a senior
lecturer/honorary Consultant and I suffered no constraints over my publications,
lectures to my students, or statements to the media. However, I became
increasingly aware after 1988 that questioning official dogma about BSE brought
difficulties to one’s career. I was myself about to retire from the Charing
Cross Hospital, where I worked as a Consultant Neuropathologist, but I observed
with horror that the good reputations of dissenting scientists in the field, not
least Dr Stephen Dealler and especially Dr Harash Narang were systematically
undermined.
snip...see more here ;
Thursday, September 30, 2010
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Wednesday, July 23, 2014
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Monday, June 02, 2014
Confirmed Human BSE aka mad cow Variant CJD vCJD or nvCJD Case in Texas
Sunday, June 29, 2014
Transmissible Spongiform Encephalopathy TSE Prion Disease North America
2014
TSS
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