Important legal notice
   
Contact   |   Search   
Headlines Published on 19 September 2005

DISEASE, RESEARCH
Title Researchers move closer to early diagnosis of prion diseases

US-based researchers, collaborating with EU scientists, have moved a step closer to developing a rapid, non-invasive test which could detect the agent causing prion diseases earlier and more sensitively than is currently possible. Such a test would enhance food safety by improving the detection of BSE and Scrapie in food animals, would allow the screening of human blood and transplant organs for vCJD and would allow scientists to estimate more accurately the number of people likely to develop vCJD.

At the height of the UK ‘Mad Cow’ epidemic many consumers wrongly assumed that all meat was BSE-infected. © Web source
At the height of the UK ‘Mad Cow’ epidemic many consumers wrongly assumed that all meat was BSE-infected.
© Web source
The research team, working out the USA, has developed an automated system to ‘amplify’ infectious prion found in central nervous system (CNS) tissue and blood (previously difficult to achieve). Infectivity can then be detected using conventional methods. A fast, simple and highly sensitive blood test for prion diseases would benefit Europe in myriad ways.

According to the team behind the new technique, it offers “promise for developing a non-invasive method for early diagnosis of prion disease” and more widespread and effective screening for transmissible spongiform encephalopathy (TSE) in general. The team acknowledges the contribution of the EU-funded collaborative research project, TSELAB, to the findings published in a recent letter to Nature Medicine, a major scientific journal.

vCJD (variant Creutzfeldt Jakob disease) the human form of BSE (bovine spongiform encephalopathy) can currently only be detected when clinical signs of disease are apparent. Earlier detection in humans would increase the effectiveness of future therapies. The test would also allow the screening of blood and organs intended for transfusion and transplantation, It could also help epidemiologists to predict more accurately the numbers of people likely to develop vCJD as a result of exposure to contaminated food or blood.

Detection of BSE in cattle or Scrapie in sheep would be easier to achieve if blood could be analysed, rather than CNS, and the increased sensitivity would further enhance food safety. Detection of infection in live sheep might also permit more targeted control strategies, in which only infected animals in a flock are culled.

The team behind the findings, headed by Claudio Soto, a Chilean neurology professor currently at the University of Texas Medical Branch (UTMB), says it can now find the rogue ‘prion’ proteins behind this disease in the blood of hamsters. The researchers are refining the method – using blood samples from British vCJD victims – to find prions in human blood. His co-authors are the Spanish neuroscientist Joaquín Castilla and Paula Saá working out of UTMB’s Neurology Department.

Misbehaving proteins
The letter describes how the scientists used an automated technique, known as protein misfolding cyclic amplification (PMCA), to amplify prion in the blood of hamsters infected with Scrapie and displaying clinical signs of disease. This amplification technique enhances the sensitivity of the subsequent, conventional detection step, a ‘western blot’.

“We show that 140 PMCA cycles leads to a 6 600-fold increase in sensitivity [to the ‘misfolded’ prions in the blood] over standard detection,” the researchers write. With two successive cycles, the sensitivity and ability to detect even small amounts of rogue proteins is massively increased by some 10 million times.

The technique, which has been likened in effect to that which forensic scientists use to amplify fragments of DNA found at crime scenes (polymerase chain reaction, or PCR), utilises sound waves to speed up the process by which prions transform normal proteins to misshapen infectious types. Cycles of sonication break up aggregates of infectious prions, enabling them to interact with unmodified protein, creating new aggregates which are then broken down again so that the process of modification proceeds more quickly. While the mechanism is different from PCR, the amplification effect is similar.

The announcement of the findings has drawn significant media interest especially in the UK where BSE – and later vCJD – has caused major concern in the agriculture and health communities.

Prion diseases are relatively rare in humans. According to the latest figures derived from EU-funded projects EURO-, NEURO- and SEEC-CJD, which are coordinating surveillance programmes for vCJD and other forms of CJD in Europe and beyond, the total number of definite and probable vCJD cases is over 150. The majority of these cases resulted from exposure to the infectious agent while in the UK. It was only in 2003 that evidence of cases of vCJD due to infected blood transfusions became available.

BSE has become a significant health problem affecting many countries, and now there is evidence that, in addition to contracting vCJD through eating BSE-contaminated meat, it may also be transmitted from human-to-human (iatrogenically) by blood transfusions. But with the new PMCA technique, there is hope that prions can be detected in the blood sooner. “We believe in six months or so we should have the technology optimised to detect prions in human blood,” Dr Soto is quoted as saying. “The next step is to make sure we can detect them in blood before the clinical symptoms appear.”

The TSELAB project, (Human Transmissible Spongiform Encephalopathies: the European Diagnostic Laboratory), acknowledged in the Nature Medicine letter, ended its three-year EU contract in August. Nevertheless, the partnership developed by the coordinator, Professor Herbert Budka of the Vienna Medical University, has established collaborations that should endure beyond EU funding.

Before moving to the USA, Dr Soto worked at Serono, a Swiss pharmaceutical research institute and partner in the Fifth Framework Programme TSELAB project. However, following his transfer, the Commission amended the funding contract to include UTMB in the project.







Source:  Nature, news reports, EU sources and UTMB


Contact:
Research Contacts page


More information:

  • Claudio Soto (UTMB site)
  • TSELAB (project website in German and English)
  • BSE blood test gives new hope (The Guardian, 29 August 2005)
  • Test raises hope of CJD screening (BBC On-line, 29 August 2005)
  • Test sul sangue per la ‘mucca pazza’
    (Corriere della Serra, 29 August 2005)



  •   >> TODAY'S NEWS    
     
      >> ALL HEADLINES