Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover possible diagnosis, treatment, vaccine for mad cow, prion diseases

02.06.2003


Research led by scientists at the U of T and Caprion Pharmaceuticals have uncovered the basis for a diagnostic, immunotherapy and vaccine, providing a way to detect and treat the brain-wasting damage of infectious prions like those found in mad cow disease and its human version, Creutzfeldt-Jakob Disease.


Microscopic image of a tissue sample from a human brain that shows a clump of infectious prions (dark pink area).
Credit: Dr. Neil Cashman of the University of Toronto.


representation showing the tyrosine-tyrosine-arginine amino acid sequence (the yellow, green and purple clumps) on the infectious prion.
Credit: Dr. Neil Cashman of the University of Toronto.



Dr. Neil Cashman, a principal investigator at U of T’s Centre for Research in Neurodegenerative Diseases and professor in the Department of Medicine (neurology) and a Caprion founder, says a vaccine approach - which would likely be of most use in animals and livestock - could prevent animals from becoming infected. For humans with diseases like classical or variant Creutzfeldt-Jakob, an immunotherapeutic would provide patients with antibodies that bind infectious prions, enabling the immune system to recognize and attack them. For both humans and animals, the diagnostic screening potential of this discovery could significantly improve the safety of the human blood and food systems.

Cashman, who also holds the Jeno Diener Chair in Neurodegenerative Diseases at U of T, says his team tried a new approach in studying infectious prions, which are particles thought to be composed of normal prion proteins that have been compromised and folded into rogue shapes. "The usual way of raising antibodies in the immune system is to grind the infectious agent up and inject it into a mouse to see if it prompts antibody production," he says. "Scientists have tried this method with prions over the past 15 years, all without success. My group decided to examine it from the sub-molecular level to determine if antibodies would recognize and react to the amino acids exposed at the surface of a prion. It was a novel idea, and when we found that our hypothesis actually worked, we were surprised and pleased." The researchers’ findings are reported online in the June 1 version of Nature Medicine.


All mammals have prion proteins, the highest levels of which are present in the brain, explains Cashman, a senior scientist at Sunnybrook and Women’s Research Institute and a neurologist in the Department of Medicine at Sunnybrook and Women’s College Health Sciences Centre. Mammals can contract prion diseases by ingesting abnormal or infectious prions. From the digestive system, these prions make their way to the brain. When an abnormal prion comes in contact with a normal prion protein, it causes the protein to misfold, thus creating a copy of the infectious prion. Cashman says the process is more akin to co-opting than replication. However, since the abnormal prion has similar characteristics to the original host protein, the immune system does not recognize it as a foreign invader and does not attack it.

In their study, Cashman and his colleagues examined the role of chemical groups in amino acids, which are called side chains. "We wanted to see whether there were side chains accessible on abnormal prions that were not accessible on the normal protein. We hypothesized that in a normal prion protein, there will be side chains buried in the interior of the molecule. When the protein converts to the abnormal form, we thought that some of these side chains would then be exposed on the molecular surface. We discovered that the newly exposed side chains of abnormal prions include a sequence composed of three amino acids - tyrosine, tyrosine and arginine (Tyr-Tyr-Arg). By raising antibodies against the Tyr-Tyr-Arg amino acid sequence, the immune system became able to recognize the abnormal prion as an invader and attack it."

"It was a ’Eureka!’ moment," he recalls. "Significantly, while the antibodies recognized the abnormal prions, they left the normal prion proteins intact."

Cashman and his team further found that the tyrosine-tyrosine-arginine amino acid sequence appears to be common among species. "Different species have different sequences of prion proteins," he says. "But this Tyr-Tyr-Arg motif appears to be the same in every species that we’ve been able to look at - humans, cattle, mice, hamsters, sheep and elk. When we applied our antibodies to the infected tissues and cells of our samples, they only bound to the abnormal prion protein in all these species."

The researchers are currently testing a possible vaccine to prion disease in mice. They plan to immunize mice with the Tyr-Tyr-Arg sequence and then infect them with prions.

"In order to treat prion diseases in the most effective way possible, it is necessary to understand the manner in which prion proteins fold into a pathological form," says Dr. Bhagirath Singh, scientific director of the Institute of Infection and Immunity of the Canadian Institutes of Health Research. "Dr. Cashman’s discovery is a vital step in understanding the causes of prion diseases and will play key a role in developing vaccines and a new generation of drugs to combat this condition."

The immediate commercial applications of the discoveries are diagnostics, as global health authorities urgently seek to ensure that beef and transfused blood are safe from Mad Cow-related infections. "Neil’s discovery represents the single most promising hope for diagnosing and treating this fatal disease," notes Lloyd M. Segal, president and CEO of Caprion. Caprion has already announced collaborations with Johnson & Johnson and IDEXX Laboratories to apply these technologies for the development of diagnostics for prion-related diseases, he adds.


Caprion provided the major funding and support for this pioneering research and own all commercial applications of the discoveries. This research was also supported by the Canadian Institutes of Health Research and McDonald’s Corp.

CONTACT:

Janet Wong
U of T Public Affairs
416-978-5949
jf.wong@utoronto.ca

Neil Cashman
Centre for Research in Neurodegenerative Diseases
416-978-1875
neil.cashman@utoronto.ca

Kathie Darlington
Caprion Pharmaceuticals Inc.
514-940-3608


Janet Wong | EurekAlert!
Further information:
http://www.caprion.com
http://www.utoronto.ca/

More articles from Agricultural and Forestry Science:

nachricht Researchers discover natural product that could lead to new class of commercial herbicide
16.07.2018 | UCLA Samueli School of Engineering

nachricht Advance warning system via cell phone app: Avoiding extreme weather damage in agriculture
12.07.2018 | Leibniz-Zentrum für Agrarlandschaftsforschung (ZALF) e.V.

All articles from Agricultural and Forestry Science >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Global study of world's beaches shows threat to protected areas

19.07.2018 | Earth Sciences

New creepy, crawly search and rescue robot developed at Ben-Gurion U

19.07.2018 | Power and Electrical Engineering

Metal too 'gummy' to cut? Draw on it with a Sharpie or glue stick, science says

19.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>