Clinical Research Studies in the UK and PNG

Lead Research Organisation: MRC Prion Unit

Abstract

Kuru is one of a closely related group of brain diseases which affect both humans and animals known as the transmissible spongiform encephalopathies or prion diseases. Animal prion diseases include scrapie, a naturally occurring disease affecting sheep and goats, which has been recognised for over 200 years and is present in many countries world-wide, and the much more recently recognised bovine spongiform encephalopathy (BSE) (mad cow disease) amongst cattle. The human prion diseases include Creutzfeldt-Jakob disease (CJD) and kuru. Kuru provides the principal experience of an epidemic human prion disease. It has steadily declined in incidence following the abrupt cessation of its route of transmission, endocannibalism, in Papua New Guinea in the 1950s. BSE transmitted to humans causes variant CJD. The unknown prevalence of infection following the extensive dietary exposure to BSE prions in the UK has led to renewed interest in kuru, particularly with respect to the range of possible incubation periods and the effect of genetic susceptibility factors. Present studies are ongoing to record the maximum incubation period for kuru. Epidemiological studies that include genetic and anthropological data are being conducted to help us fully understand the kuru epidemic and its implications for the variant Creutzfeldt-Jakob disease epidemic.

Technical Summary

Kuru is one of a closely related group of neurodegenerative conditions which affect both humans and animals known as the transmissible spongiform encephalopathies or prion diseases. Animal prion diseases include scrapie, a naturally occurring disease affecting sheep and goats, which has been recognised for over 200 years and is present in many countries world-wide, and the much more recently recognised bovine spongiform encephalopathy (BSE) amongst cattle. The human prion diseases have been traditionally classified into Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Sheinker syndrome (GSS) and kuru. Kuru provides the principal experience of an epidemic human prion disease. It has steadily declined in incidence following the abrupt cessation of its route of transmission, endocannibalism, in Papua New Guinea in the 1950s. The arrival of the novel acquired prion disease, variant CJD, and the unknown prevalence of infection following the extensive dietary exposure to BSE prions in the UK, has led to renewed interest in kuru, particularly with respect to the range of possible incubation periods and the effect of genetic susceptibility factors. That the incubation period of infection acquired by dietary exposure to human prions can exceed 50 years, as found in kuru, suggests the need for caution with respect to predictions of vCJD epidemic size and duration based on the numbers of clinical cases seen to date. Infection of humans with cattle BSE prions involves cross-species, rather than within-species transmission, which would further increase the mean and range of incubation periods. The research activities have seven major aims. (1) Identify and study all remaining kuru patients: document the maximum incubation periods: We have studied the clinical features of recent kuru patients and compared clinical and other diagnostic features with other human prion diseases, notably iatrogenic and variant CJD. Surveillance for new patients is ongoing. (2) Epidemiological analysis of kuru records: Data will be analysed for standard epidemiological variables and differences in geographical area. (3) Document mortuary feast practices and traditional beliefs of the aetiology of kuru by interview of surviving participants and other members of the Fore community: A large number of interviews have been conducted and are being analysed. More interviews are planned to expand the cultural and geographical range of the study and to probe deeper into the details of the mortuary rites. (4) To investigate for any evidence of maternal or other routes of kuru transmission: From the data available we conclude that maternal transmission was not a feature of kuru. The data on mortuary practices do not support a high probability of parenteral transmission. Thus the common route of transmission was undoubtedly oral. (5) Genetic susceptibility: details of laboratory studies are given under Unit Human Molecular Genetics research programme. (6) Peripheral pathogenesis, tissue distribution and investigation of possibility of asymptomatic carriers of kuru: Tissues obtained from a kuru autopsy are under intense investigation. We will interview elderly survivors of the kuru epidemic in all affected linguistic groups to look at factors affecting the transmission of kuru. We aim to obtain autopsies when these older people die to determine whether any were asymptomatic carriers of kuru. (7) Data archive and bibliography: A full inventory will be made of all the kuru and kuru-related files. When the appropriate equipment is available archival and contemporary footage will be combined and edited on digital format for making teaching films on kuru, of varying length and complexity suitable for medical educational purposes.

Publications

10 25 50

publication icon
Alpers MP (2007) A history of kuru. in Papua and New Guinea medical journal

publication icon
Alpers MP (2008) Review. The epidemiology of kuru: monitoring the epidemic from its peak to its end. in Philosophical transactions of the Royal Society of London. Series B, Biological sciences

publication icon
Alpers MP (2008) Some tributes to research colleagues and other contributors to our knowledge about kuru. in Philosophical transactions of the Royal Society of London. Series B, Biological sciences

publication icon
Angus-Leppan H (2013) Autoantibodies in sporadic Creutzfeldt-Jakob disease. in JAMA neurology

publication icon
Bonham LW (2018) CXCR4 involvement in neurodegenerative diseases. in Translational psychiatry

publication icon
Brandner S (2008) Central and peripheral pathology of kuru: pathological analysis of a recent case and comparison with other forms of human prion disease. in Philosophical transactions of the Royal Society of London. Series B, Biological sciences

 
Description Attendance of Committees
Geographic Reach National 
Policy Influence Type Participation in advisory committee
 
Description Briefing to PUS for Health & CMO on vCJD research
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description Briefing to PUS for Health re current CJD research
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
 
Description Clinical research output
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Description MRC Prion Disease Rating scale
Geographic Reach Multiple continents/international 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact The MRC rating scale enables physicians to monitor the decline of patients suffering from CJD, both in person and remotely
 
Description Meeting with MP
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
 
Description Parliamentary Select Committee
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
 
Description NIHR Biomedical Research Unit for Dementia: Molecular Mechanisms theme
Amount £611,666 (GBP)
Organisation Barts Health NHS Trust 
Department NIHR Biomedical Research Unit
Sector Academic/University
Country United Kingdom
Start 04/2012 
End 03/2017
 
Description National Prion Monitoring Cohort
Amount £4,800,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2008 
End 03/2015
 
Description UCLH Biomedical Research Centre
Amount £2,700,000 (GBP)
Organisation National Institute for Health Research 
Department UCLH/UCL Biomedical Research Centre
Sector Public
Country United Kingdom
Start 04/2012 
End 04/2015
 
Description Clinical Trial and Cohort studies with MRC CTU 
Organisation Medical Research Council (MRC)
Department MRC Clinical Trials Unit
Country United Kingdom 
Sector Public 
PI Contribution MRC CTU contribute statistical and clinical trials expertise. The data collection is done by National Prion Clinic staff
Collaborator Contribution MRC CTU contribute statistical and clinical trials expertise
Impact The first large clinical trial in human prion disease. 19081515
 
Description Kuru Field Studies Project 
Organisation Papua New Guinea Institute of Medical Research
Country Papua New Guinea 
Sector Public 
PI Contribution We have provided the supervision of all field studies and have led the field team in epidemiological surveillance, in clinical and genetic studies, and in ethnographic and human behavioural investigations. We have provided training to the staff of the project.
Collaborator Contribution They have provided an administrative base in Goroka for our field studies and a field base in Waisa in the South Fore. They have facilitated our contacts with the health and other authorities in Papua New Guinea. They have provided logistical support to our work and helped to ensure good relations with local communities.
Impact The collaboration has produced important information about a completed epidemic of human prion disease, and demonstrated the long incubation periods that can occur in human prion disease. It has discovered a protective genetic variant that the kuru epidemic has selected for, a dramatic demonstration of human evolution in action. The epidemic has led to a balancing selection in a related human genetic polymorphism and further investigation of this has provided evidence for kuru-like epidemics in the remote human past. All the publications in section 1 have resulted, to a lesser or larger extent, from this collaboration. This collaboration is multi-disciplinary, with significant contributions from the disciplines of clinical neurology, neuropathology, molecular biology, epidemiology, human genetics and anthropology.
 
Description Neuroimaging of prion disease 
Organisation Medical Research Council (MRC)
Department MRC Clinical Trials Unit
Country United Kingdom 
Sector Public 
PI Contribution MRC CTU contribute statistical and clinical trials expertise. The clinical trial and similar studies are conducted by National Prion Clinic staff
Collaborator Contribution Expertise in neuroimagingMRC CTU contribute statistical and clinical trials expertise
Impact The first large clinical trial in human prion diseases. 19081515
 
Description Neuroimaging of prion disease 
Organisation University College London Hospitals NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution MRC CTU contribute statistical and clinical trials expertise. The clinical trial and similar studies are conducted by National Prion Clinic staff
Collaborator Contribution Expertise in neuroimagingMRC CTU contribute statistical and clinical trials expertise
Impact The first large clinical trial in human prion diseases. 19081515
 
Description Neurophysiology of prion disease 
Organisation University College London Hospitals NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution National Prion Clinic staff collect clinical and investigation data.
Collaborator Contribution EEG and EMG study of prion disease patients
Impact Contribution to National Prion Monitoring Cohort study publications
Start Year 2007
 
Title Blood Test for vCJD 
Description A screening test that enables precise detection of vCJD infection. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Small-scale adoption
Year Development Stage Completed 2011
Development Status Under active development/distribution
Impact A screening test that enables precise detection of vCJD infection. 
 
Title Genetic testing of dementia genes 
Description Clinical service for genetic testing of dementia genes received from both national and international institutions 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Wide-scale adoption
Development Status Under active development/distribution
Impact Clinical service for genetic testing of dementia genes received from both national and international institutions 
 
Description AAN Annual Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented talk to Annual Meeting of the American Academy of Neurology "Development of rational therapeutics for prion infection and its relevance to Alzheimer's disease"
Year(s) Of Engagement Activity 2016
 
Description ANA lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented a lecture at the American Neurological Association AGM. "Prion Diseases: The classical view"
Year(s) Of Engagement Activity 2015
 
Description Clinic Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Update on patients and carers on the Unit's work
Year(s) Of Engagement Activity 2016
 
Description Comment and edits for an article published in The Global Mail (13 November 2012) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Comment and edits for an article entitled 'Last Laughing Death' on Professor Michael Alpers' career researching Kuru in Papua New Guinea

Publication in Global Mail, an international online publication. Such articles serve to increase public awareness of research.
Year(s) Of Engagement Activity 2012
 
Description Interview for BBC Newsnight (29 March 2011) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact An interview BBC newsnight regarding surgical decontamination and CJD infection. The interview was broadcast as part of a special feature on the issue.

The interview served to raise public awareness of the issues surrounding surgical decontamination.
Year(s) Of Engagement Activity 2011
 
Description Interview for BBC Radio 4 Today (19 November 2009) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Interview for Today, BBC Radio 4, regarding the publication of the following paper

Mead S, Whitfield J, Poulter M, Shah P, Uphill J, Campbell T, Al-Doujaily H, Hummerich H, Beck J, Mein C, Verzilli C, Whittaker J, Alpers M, Collinge J. A novel protective prion protein variant co-localises with kuru exposure. N Engl J Med 2009; 361: 2056-65.

The interview, along with a press release, generated significant media interest including articles in national newspapers such as the Times

Interview and increased media interest serve to widen public awareness of the Unit's work.
Year(s) Of Engagement Activity 2009
 
Description Interview for Daily Telegraph (27 April 2013) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Interview for the Daily Telegraph regarding Human Exposure to BSE and prevalence of CJD. Resulted in a front page news item in the Daily Telegraph.

Prompted further media enquiries increasing public awareness of the issue.
Year(s) Of Engagement Activity 2013
 
Description Interview with Channel 4 News (14 January 2012) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Interview with Channel 4 News regarding the Prion Unit and The National Prion Clinic offering a CJD blood test.

Interview served to raise public awareness of the test
Year(s) Of Engagement Activity 2012
 
Description Interview with Daily Mail (1 November 2011) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Interview with the Daily Mail on infectious prions and blood donors. Resulted in an article being published in a National Newspaper.

The interview served to raise public awareness of the issue of Prion disease carriers and blood donations.
Year(s) Of Engagement Activity 2011
 
Description Interview with Sky News (3 February 2011) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Interview with Sky News regarding the Unit's CJD Blood Test.

Interview raised public awareness of the blood test and the Unit's work.
Year(s) Of Engagement Activity 2011
 
Description Invited presentation to USA patient group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Invited presentation to USA patient group

N/A
Year(s) Of Engagement Activity 2009,2011,2012
 
Description MRC Centenary Open Day (20 June 2013) 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Approximately 100 members of the public attended the Prion Unit's Centenary Open Day on 20 June 2013. The presentations prompted a series of questions from patient's families regarding the Unit's current research and aims.

The open date resulted in enquiries from the National Media, including a filmed television interview for ITN News.
Year(s) Of Engagement Activity 2013
 
Description MRC Prion Unit and NHS National Prion Clinic Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Detailed presentation on research strategy and update for patients, familes, carers and health professionals with question and answer session, lab tours and informal discussions with research staff and students

Obtaining feedback on our work, communicating our research and services, building good relationships with our patient group
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description Media Interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Interviewed by journalist from Bio Century Publications; regarding published journal article on prion resistance among the Fore of PNG
Year(s) Of Engagement Activity 2015
 
Description Media interest (Comment for Readers Digest article) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Provided comment on human exposure to BSE for an article published in Readers Digest.

Raising awareness of the work undertaken by MRC
Year(s) Of Engagement Activity 2013
 
Description Member of special panel during CJD Support Network (Australia) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Served as panel member on special session entitled 'Patient Care, Diagnostics, Genetic CJD and Treatment Trails'. Discussions were conducted in front of an audience of 130 patients and family members

Patient group feedback indicated heightened knowledge of this disease as a result of workshop
Year(s) Of Engagement Activity 2013
 
Description National Prion Clinic, Patients and Families Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Talk sparked questions and discussions afterwards & obtaining feedback from patients and their families.

Feedback resulted in our providing increased councelling services.
Year(s) Of Engagement Activity 2014
 
Description Patient/Families Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Clinic open day, provided an update on the Unit's research and objectives.
Year(s) Of Engagement Activity 2015
 
Description Podcast 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Recorded podcast for Nature Podcast re journal article on kuru
Year(s) Of Engagement Activity 2015
 
Description Presented to CJD Foundation Family Support Group 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Approx 50 patient family members attended talk.

Patient group feedback indicated heightened knowledge of this disease as a result of presentation.
Year(s) Of Engagement Activity 2010,2011,2012,2013
 
Description Press Release for NEJM Kuru Paper (18 November 2009) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Press release for the following paper:

Mead S, Whitfield J, Poulter M, Shah P, Uphill J, Campbell T, Al-Doujaily H, Hummerich H, Beck J, Mein C, Verzilli C, Whittaker J, Alpers M, Collinge J. A novel protective prion protein variant co-localises with kuru exposure. N Engl J Med 2009; 361: 2056-65.

Media interest including an interview for the BBC Radio 4 and article in The Times newspaper. Served to increase public awareness of the Unit's work.
Year(s) Of Engagement Activity 2009
 
Description Press release for Dementia Chip Paper (20 February 2013) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Press release for the following paper:

Beck J, Pittman A, Adamson G, Campbell T, Kenny J, Houlden H, Rohrer JD, de Silva R, Shoai M, Uphill J, Poulter M, Hardy J, Mummery CJ, Warren JD, Schott JM, Fox NC, Rossor MN, Collinge J, Mead S. Validation of next generation sequencing technologies in genetic diagnosis of dementia. Neurobiol Aging 2013, (published online ahead of print).

Increased media awareness of paper.
Year(s) Of Engagement Activity 2013
 
Description Press release for Lancet Blood Test paper (1 February 2011) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Press release regarding the publication of the following paper:

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

The press release generated a wide-range of media interest resulting in articles published in national newspapers and websites including: The Guardian, BBC News, The Telegraph, The Express, The Daily Mail, The Scotsman and The MIrror.

The resulting media coverage served to raise public awareness of the paper and the Unit's work.
Year(s) Of Engagement Activity 2011
 
Description Press release for PNAS paper (26 July 2009) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Press release for the following paper:

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



Increased media awareness including this video http://www.youtube.com/watch?v=eEC8Ifi6cv0 which raises public awareness of Unit's work
Year(s) Of Engagement Activity 2010
 
Description Radio Interview, Today Programme BBC Radio 4 (3 February 2011) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Interviewed on the Today programme, BBC Radio 4, about the publication of the Unit's work on a new CJD blood test. The interview, along with a press release, generated a series of articles in national newspapers and websites.

The interview served to increase public awareness of the blood test and CJD prevalence.
Year(s) Of Engagement Activity 2011
 
Description Royal Society Meeting on kuru - discussion with media 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Discussion with representatives of the media about the meeting to celebrate the end of kuru attended by collaborators and those effected by the disease.

Article in "Times" newspaper was published
Year(s) Of Engagement Activity 2007
 
Description Teaching / lectures 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Health professionals
Results and Impact National Prion Clinic staff visit an NHS facility and disseminate good practice and update staff on our research objectives. Around 30-50 of these visits are done in a typical year. At a minimum this involves staff at a small Unit like a ward or nursing home, but might also include a presentation to a University Medical School entire staff.

Increased awareness.
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010