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MRC Prion Unit
From fundamental research to prevention and cure

Molecular diagnostic strategies in prion disease


The majority of the UK population and a lesser proportion of continental European and the rest of the world have been exposed to mad cow disease or BSE contaminated foods and this has resulted in the new human disease variant CJD (vCJD). Although the number of patients has remained small, the number of people infected but without any signs of illness is thought to exceed 30,000 in the UK alone. Infected individuals may never show any signs of disease or this can take over 50 years to develop. However, they are themselves infectious and there is a risk of spreading the disease through the contamination of medical and dental instruments; the use of contaminated blood for transfusion and the transplantation of infected organs and tissues. All of these dangers pose significant challenges for the protection of public health and measures currently in place cost 10’s of millions of pounds per annum in the UK alone.

To date there have been four confirmed cases of vCJD resulting from the transfusion of contaminated blood and several thousand patients are known to have received contaminated blood products who are considered by the UK Department of Health to be at high risk. All of these problems can be avoided if simply tests were available to detect CJD infection in the peripheral blood of carriers.

Significant effort over several years within the Department of Neurodegenerative Disease and the MRC Prion Unit has focused on identifying effective small molecule therapeutics in collaboration with Glaxo-Smith-Kline (GSK) and to advance initial Unit studies showing immunotherapy can be highly effective against prion infection. The prospect of future clinical trials necessitates parallel advances in both early diagnosis of infection and the establishment of infection biomarkers that change with the progress of disease and potential remission following treatment.

Human PrPc

Prion disease is defined by a characteristic change that occurs to one of the body’s normal proteins and the detection of this altered protein or PrPSc prion can be used to show someone has CJD. Unfortunately the amounts of prion are very low in easily obtained samples such as blood and urine, and are difficult to tell apart from the large amounts of the normal protein that are always present in both healthy and infected people.

A key achievement of my group has been the first demonstration of the ability to detect vCJD infection in patient blood samples and the development of a highly accurate blood test. Critical to the utility and benefit of a test for vCJD is the specificity of the assay. Any significant number of wrong results from other would outweigh the benefits of detecting CJD. By testing thousands of blood samples provided by the American Red Cross from healthy blood donors and hundreds of samples from patients with other neurological diseases we have established that our blood test is 100% specific. 

Normal samples were obtained from the American Red Cross (USA Normals) or UK NHSBT (UK Normals) and were representative of the respective donor pools. Non-prion neurodegenerative disease samples (Other Neurol.) were from patients with a confirmed diagnosis other than prion disease.National Prion Clinic referrals (NPC Referrals) were samples from patients where a diagnosis of prion disease was likely. *Two patients with a referral to the National Prion Clinic tested positive. Both had a diagnosis of sporadic CJD

Our blood assay has been introduced for service evaluation as a diagnostic test by the UCLH NHS Trust at the NHS National Prion Clinic. The performance of the test and its reporting has been excellent and the test is now under consideration for full adoption by UCLH NHS Trust.

We are trying different ways of detecting this rare altered protein which accumulates as ordered aggregates. One approach is to copy the way the prion reproduces itself in the human body during disease. This allows us to ‘amplify’ the very small amounts of prion in patient samples into large amounts that can be easily detected using conventional laboratory tests. In doing so we are also gaining insights into the fundamental processes of prion replication that distinguish this particular protein misfolding event from those involved in other diseases that produce very similar aggregated proteins that do not infect others.

Our research requires interaction with other Unit programmes working to identify genetic modifiers of susceptibility to infection (Dr Simon Mead) and incubation period (Dr Sarah Lloyd). We work closely with Dr Jonathan Wadsworth who is leading research to purify the infectious agent and by combining methods for purification with the ability to replicate prions in a test tube we are aiming to define the molecular mechanisms of prion replication. Both Dr Wadsworth’s group and ourselves have close interactions with Programme 7 and we attempting to apply all of our research to generate synthetic prions and determine their molecular organisation and atomic structure.

Current Group Members:

Dr Connie Luk
Mrs Samantha Jones
Mrs Claire Thomas


Developing early diagnostics for prion diseases
Jackson GS, Mead S, Collinge J.  Neurodegener Dis Manag 2013; 3: 53-60.

Peer reviewed articles:
Neurofilament light chain and tau concentrations are markedly increased in the serum of patients with sporadic Creutzfeldt-Jakob disease, and tau correlates with rate of disease progression. 
Thompson AGB, Luk C, Heslegrave AJ, Zetterberg H, Mead SH, Collinge J, Jackson GS J Neurol Neurosurg Psychiatry. 2018 Feb 27.


Diagnosing Sporadic Creutzfeldt-Jakob Disease by the Detection of Abnormal Prion Protein in Patient Urine. Luk C, Jones S, Thomas C, Fox NC, Mok TH, Mead S, Collinge J, Jackson GS. JAMA Neurol. 2016 Oct 3. doi: 10.1001/jamaneurol.2016.3733. PubMed PMID: 27699415.

Physical, chemical and kinetic factors affecting prion infectivity.  Properzi F, Badhan A, Klier S, Schmidt C, Klöhn PC, Wadsworth JDF, Clarke AR, Jackson GS, Collinge J.  Prion 2016; doi: 10.1080/19336896.2016.1181250


Preclinical detection of infectivity and disease-specific PrP in blood throughout the incubation period of prion disease.
Sawyer EB, Edgeworth JA, Thomas C, Collinge J, Jackson GS. Sci Rep. 2015 Dec 3;5:17742. doi: 10.1038/srep17742.

A systematic investigation of production of synthetic prions from recombinant prion protein.
Schmidt C, Fizet J, Properzi F, Batchelor M, Sandberg MK, Edgeworth JA, Afran L, Ho S, Badhan A, Klier S, Linehan JM, Brandner S, Hosszu LL, Tattum MH, Jat P, Clarke AR, Klöhn PC, Wadsworth JD, Jackson GS, Collinge J. Open Biol. 2015 Dec; 5(12). pii: 150165. doi: 10.1098/rsob.150165.


Blood test for variant Creutzfeldt-Jakob Disease – reply
Jackson GS, Burk-Rafel J, Mead S, Collinge J. JAMA Neurol 2014: 71(8):1054-5.

Population Screening for Variant Creutzfeldt-Jakob Disease Using a Novel Blood Test: Diagnostic Accuracy and Feasibility Study
Jackson G, Burk-Rafel J, Edgeworth J, Sicilia A, Abdilahi S, Korteweg J, Mackey J, Thomas C, Wang G, Schott J, Mummery C, Chinnery P, Mead S, Collinge J. JAMA Neurol 2014; 71: 421-8.

Variant Creutzfeldt-Jakob disease with extremely low lymphoreticular deposition of prion protein
Mead S, Wadsworth JDF, Porter MC, Linehan J, Pietkiewicz W, Jackson GS, Brandner S, Collinge J.  JAMA Neurol 2014; 71: 340-3.

A highly specific blood test for vCJD
Jackson GS, Burk-Rafel J, Edgeworth JA, Sicilia A, Abdilahi S, Korteweg J, Mackey J, Thomas C, Wang G, Mead S, Collinge J. Blood 2014; 123: 452-3.


Detection of prion infection in variant Creutzfeldt-Jakob disease: a blood-based assay.
Edgeworth JA, Farmer M, Sicilia A, Tavares P, Beck J, Campbell T, Lowe J, Mead S, Rudge P, Collinge J, Jackson GS. Lancet 2011; 377: 487-93.

A Standardised comparison of commercially available prion decontamination reagents using the standard Steel Binding Assay
Edgeworth JA, Sicilia A, Linehan J, Brandner S, Jackson GS, Collinge J.  J Gen Virol 2011; 92: 718-26.

Pharmacological chaperone for the structured domain of human prion protein
Nicoll A, Trevitt C, Risse E, Quaterman E, Ibarra AA, Wright C, Jackson GS, Sessions R, Farrow M, Waltho J, Clarke A, Collinge J.  Proc Natl Acad Sci USA 2010; 107; 17610-5.

The H187R mutation of the human prion protein induces conversion of recombinant prion protein to PrPSc-like form
Hosszu L, Tattum H, Jones S, Trevitt CR, Wells MA, Waltho JP, Collinge J, Jackson GS, Clarke AR.
Biochemistry 2010; 49: 8729-38.

Spontaneous generation of mammalian prions
Edgeworth J, Gros N, Alden J, Joiner S, Wadsworth JDF, Linehan J, Brandner S, Jackson GS, Weissmann C, Collinge J.  Proc Natl Acad Sci USA 2010; 107: 14402-6.

A highly sensitive immunoassay for the detection of prion-infected material in whole human blood without the use of proteinase K.
Tattum MH, Jones S, Pal S, Khalili-Shirazi A, Collinge J, Jackson GS. Transfusion 2010; 50: 2619-27.

PRNP allelic series from 19 years of prion protein gene sequencing at the MRC Prion Unit
Beck JA, Poulter M, Campbell TA, Adamson G, Uphill JB, Guerreiro R, Stephens JC, Jackson GS, Manji H, Collinge J, Mead S.  Hum Mut 2010; 31: E1551- 63.

Superoxide dismutase 1 and tgSOD1 mouse spinal cord seed fibrils, suggesting a propagative cell death mechanism in amyotrophic lateral sclerosis
Chia R, Tattum HM, Jones S, Collinge J, Fisher EMC, Jackson GS.  PlosOne 2010; 5: e10627.

The legs at odd angles (Loa) mutation in cytoplasmic dynein ameliorates mitochondrial function in SOD1G93A mouse model for motor neuron disease
El Kadi AM, Bros-Facer V, Deng W, Philpott A, Stoddart E, Banks G, Jackson GS, Fisher EM, Duchen MR, Greensmith L, Moore AL, Hafezparast M.  J Biol Chem 2010; 285: 18627-39.

Modification of superoxide dismutase 1 (SOD1) properties by a GFP tag--implications for research into amyotrophic lateral sclerosis (ALS)
Stevens JC, Chia R, Hendriks WT, Bros-Facer V, van Minnen J, Martin JE, Jackson GS, Greensmith L, Schiavo G, Fisher EM.  PLoS ONE 2010; 5: e9541.

Discrimination between prioninfected and normal blood samples by protein misfolding cyclic amplification
Tattum MH, Jones S, Pal S, Collinge J, Jackson GS. Transfusion 2010; 50: 996-1002.


The R1441C mutation alters the folding properties of the ROC domain of LRRK2
Li Y, Dunn L, Greggio E, Krumm B, Jackson GS, Cookson MR, Lewis PA, Deng J.
Biochim Biophys Acta 2009; 1792: 1194-7.

Conformational properties of beta -PrP
Hosszu LL, Trevitt CR, Jones S, Batchelor M, Scott DJ, Jackson GS, Collinge J, Waltho JP, Clarke AR.  J Biol Chem 2009; 284: 21981-90.

Crystal structure of human prion protein bound to a therapeutic antibody
Antonyuk SV, Trevitt CR, Strange RW, Jackson GS, Sangar D, Batchelor M, Cooper S, Fraser C, Jones S, Georgiou T, Khalili-Shirazi A, Clarke AR, Hasnain SS, Collinge J. Proc Natl Acad Sci USA 2009; 106: 2554-8.

Highly sensitive, quantitative cell-based assay for prions adsorbed to solid surfaces
Edgeworth JA, Jackson GS, Clarke AR, Weissmann C, Collinge J.  Proc Natl Acad Sci USA 2009; 106: 3479-83.

A role of cellular prion protein in programming T-cell cytokine responses in disease
Ingram RJ, Isaacs JD, Kaur G, Lowther DE, Reynolds CJ, Boyton RJ, Collinge J, Jackson GS, Altmann DM.  FASEB J 2009; 23: 1672-84.

Folding kinetics of the human prion protein probed by temperature jump.
Hart T, Hosszu LL, Trevitt CR, Jackson GS, Waltho JP, Collinge J, Clarke AR.
Proc Natl Acad Sci USA 2009; 106: 5651-6.

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