Ikerbasque News

Ikerbasque researcher: Joaquín Castilla

A New Way of Controlling the Prionic Epidemic Affecting Deer in the USA is Opened

This discovery, made in collaboration with the University of Kentucky (USA), has been published in the prestigious 'Science' magazine.

Together with researchers at the University of Kentucky, Joaquín Castilla, the Ikerbasque Researcher at CICbiogune has discovered a new way to control the stability of certain types of prion (the pathogenic agents responsible for transmissible spongiform encephalopathy or TSEs) by selecting specific proteins. This opens up a new opportunity to control prionic disease in deer, which has become epidemic in the USA and Canada. Last week, the prestigious scientific magazine Science published the discovery.

While the most widespread prionic disease in Europe is scrapie in sheep and goats, together with bovine spongiform encephalopathy, or mad cow disease, which appeared in the 1990's, in the USA deer prions are of most concern to the scientific community. Although there is no statistical evidence that deer prions can infect human beings, the disease continues to spread in wild animals across numerous States in the USA and has already reached some States in Canada.
Chronic Wasting Disease (CWD) is a transmissible spongiform encephalopathy that affects wild and domestic ungulates. Deer prions infect various different kinds of deer, most commonly Mule deer and Canadian dear. The first symptoms diagnosed were found in a mule deer (Odocoileus hemionus hemionus) in captivity in Colorado (USA) in 1967.

Epidemiological data point to CWD being a self-sustaining disease and it seems that it can be horizontally transmitted in captive populations. The latest research indicates that prion transmission in wild populations may occur through contaminated urine, faeces and saliva.

The epidemic's importance has meant that the disease is being investigated at the Laboratorio de Priones de la Unidad de Proteómica (Prion Laboratory at the Proteomics Unit) of the CIC bioGUNE which was launched at the beginning of 2010 in the Bizkaia Technological Park under the direction of Ikerbasque researcher Joaquín Castilla, with the main aim of "furthering our knowledge of transmissible spongiform encephalopathies (TSEs)."

The Role of Prion Strains

The CIC bioGUNE researchers' (who formed part of an international team co-ordinated by Professor Glenn Telling at the University of Kentucky) discovery has deepened our understanding of the role of the different properties of prion strains in transmitting and spreading a prionic disease, something that was previously unknown.

Transgenic mice susceptible to prion disease in deer were designed and generated for the study.  These animals enabled researchers to identify two biologically distinguishable CWD prion strains, which led to the conclusion that both prionic strains are interrelated. While the transgenic mice designed to replicate Canadian deer prions demonstrated a stable propagation of each of the prionic strains, the transgenic mice designed to replicate Mule deer prions propagated an unstable mix of CWD strains, impairing separation through their biochemical properties.

This study is important as this is the first time that a single difference in the primary sequence of amino-acids in the protein responsible for prionic diseases (Canadian deer verses Mule deer) has been demonstrated, enabling the selection of prionic strains. This discovery reveals new information about the possibility of controlling the stability of some prionic strains by modifying the primary structure of the protein responsible for the disease. The study also reveals the existence of at least two kinds of CWD strain with clearly differentiated pathogenic behaviour for the first time.

In the last decade, considerable progress has been made in our knowledge of prions.  Bovine spongiform encephalopathy in Europe ("mad cow disease") has led to an increase in the number of research teams dedicated to this kind of infectious agent. However, prions remain the great unknowns. In Castilla's opinion, prions are probably "one of nature's most intriguing pathogenic agents, as the fact that their supposed composition relates them to a single protein and the appearance of clearly distinguishing strains gives them incomparable scientific value."

Their reproductive mechanism is similar to the possible mechanism in the progress of diseases like Alzheimer's or Parkinson's, among others, making them a unique pathogen. "But if we also consider the fact that we still don't know what a prion is, prions become an irresistible research subject for people like my team and myself," concludes Castilla.

One of the great unknowns in the field of prionic diseases, to which Prof. Castilla's team is dedicated, is how a single protein is able to infect some species and not others. Although great advances are being made thanks to new technologies that have recently become available, there is still a long way to go.