PRION 2017 CONFERENCE P120 Early preclinical detection of prions in blood of macaques peripherally infected with the variant CJD agent
P120 Early preclinical detection of prions in blood of macaques peripherally infected with the variant CJD
agent.
Luis Concha1,2,Claudio Soto1
1University Of Texas, Houston, United States, 2Universidad de los Andes, Santiago, Chile
Aim: Preclinical detection of prions in blood of experimentally infected non-human primates.
The detection of prions in blood of patients affected by variant Creutzfeldt-Jakob disease (vCJD) has been recently achieved, by means of the protein misfolding cyclic amplification (PMCA) technique (Concha- Marambio et. al., 2016). Moreover, a few blood samples were shown to contain prions before disease onset (Bougard et. al. 2016). However, the unknown time of infection makes impossible to determine when in the incubation period prions can be detected in blood. Thus, we studied blood samples longitudinally collected from 3 macaques infected with the macaque adapted vCJD agent (m-vCJD).
Methods: Three macaques were peripherally infected with m-vCJD (McDowell et. al., 2016). Blood was collected longitudinally, starting 2 months post inoculation (mpi) until the endpoint of the disease. The samples were divided in three panels: early preclinical (2 to 12 mpi), late preclinical (12 mpi to onset) and clinical (onset to final bleed). These samples were kindly provided by Dr Luisa Gregory as de-identified samples.
The PMCA protocol previously used was optimized to detect prions in blood of vCJD patients, for the detection of m-vCJD prions in macaque blood, using human PrP from transgenic mice as substrate. The substrate was supplemented with 100 ug/ml heparin and few modifications were introduced into the PMCA protocol.
Results: m-vCJD prions from macaque brain homogenate (BH) were amplified at similar efficiencies vCJD prions (10-10 to 10-11 dilutions of BH). Prions were readily detected in whole blood, buffy coat and plasma during the clinical phase of the disease. Preclinical samples were more challenging to amplify. However, after PMCA optimization, we could detect with high sensitivity and specificity all the early and late preclinical samples. Our results show that m-vCJD prions from macaque blood can be detected at least ~800 days before the onset of disease.
Conclusions: PMCA was adapted for the efficient amplification of m-vCJD prions present in blood of macaques peripherally challenged with the vCJD agent. Our results suggest that PMCA can detect prions in blood more than 800 days before onset with high sensitivity and specificity. Since the first sample was collected 2 mpi and it was positive, PMCA can probably detect prions in blood weeks after inoculation. Overall, our results show the consistent and reproducible preclinical detection of prions in macaques, which suggest that this protocol could be used in humans for pre-symptomatic detection of carriers infected with vCJD prions.
DISORDERS PRION 2017 DECIPHERING NEURODEGENERATIVE
DISORDERS PRION 2017 DECIPHERING NEURODEGENERATIVE
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2015 PDA Virus & TSE Safety Forum Meeting Report
>>>Recently transmission of prions from blood of patients with sporadic CJD to humanized mice could be demonstrated.<<<
>>>Further-on, urine samples of a control population (normal and neurological population) showed no signal in the study; *** however, in samples from patients with sporadic CJD and vCJD, a signal was detected in both patient populations.<<<
Meeting Report: 2015 PDA Virus & TSE Safety Forum
Tuesday, March 11, 2014
Science and Technology Committee Oral evidence: Blood, tissue and organ screening, HC 990 Wednesday 5 March 2014 SPORADIC CJD
Actually, it is nearer 2 per million per year of the population will develop sporadic CJD, but your lifetime risk of developing sporadic CJD is about 1 in 30,000. So that has not really changed. When people talk about 1 per million, often they interpret that as thinking it is incredibly rare. They think they have a 1-in-a-million chance of developing this disease. You haven’t. You’ve got about a 1-in-30,000 chance of developing it.
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WHY THE UKBSEnvCJD ONLY THEORY IS SO POPULAR IN IT'S FALLACY, £41,078,281 in compensation REVISED
2001 FDA CJD TSE Prion Singeltary Submission
*** U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
Terry S. Singeltary Sr.
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