Understanding Prion Diseases : Part 2

by National Institute of Health

(Page 2 of 2)

In another study RML scientists used a new methodology to determine the size of the smallest infectious prions. These results demonstrate that the minimal size of the infectious material is equivalent to 5 to 10 prion protein molecules. It is possible, but still to be proved, that these smallest infectious fractions are more infectious than the larger aggregates.

RML scientists are working to insert genes into mice that would allow the mice to carry the prion protein of deer and elk. These mice would react to a prion protein infection as a deer or an elk would. Thus, scientists can study the disease in these mice rather than in the larger animals, which are much more expensive and labor-intensive to maintain.

At Colorado State University, NIAID has established an emerging diseases research center focused on studying chronic wasting disease. This center is investigating the mechanics of chronic wasting disease infection in deer and elk, especially in the lymph nodes of their immune systems. Such studies underlie the search for improved diagnostics and therapies. The researchers also will seek to better understand the entire spectrum of disease transmission and under what circumstances chronic wasting disease might "jump" to other species. In addition, scientists at the center are working on a possible vaccine to prevent the spread of chronic wasting disease in deer and elk.

To assist investigators in obtaining needed materials to study TSE diseases, NIAID has created a TSE repository with joint funding from the National Institute of Neurological Disorders and Stroke. The repository will help researchers obtain standard biochemical reagents and animals with genetic modifications for use in prion protein research.

Cross-Species Transmission

At RML, studies are ongoing to understand the mechanisms by which TSE infections cross species. Experiments have demonstrated that species once thought to be resistant to certain TSE strains can be life-long carriers of the infection without ever becoming sick. RML scientists are also investigating whether chronic wasting disease can be transmitted from deer or elk to monkeys if monkeys eat brain matter from deer or elk that are infected with chronic wasting disease. That knowledge would provide valuable insight into whether chronic wasting disease could be transmitted to humans.

Therapeutic Approaches

Although there are no known ways to treat TSE diseases, scientists around the world are working to develop treatments. Using infected tissue culture cells for fast initial screening, NIAID researchers have tested thousands of compounds and identified hundreds of molecules that inhibit the formation of the abnormal form of prion protein. Further testing of the most potent of these inhibitors has revealed several that can prolong the lives of rodents if treatments are begun near the time of infection. Researchers at RML, and at Utah State University through a contract with NIAID, are testing these compounds in animals. Other groups are further testing two of the inhibitors in Creutzfeldt-Jakob disease patients. However, no compounds have proven to have therapeutic effects after the onset of clinical signs of disease.

RML researchers have also identified antibodies and short synthetic protein molecules (fragments of prion protein) that can block the conversion of normal prion protein to the abnormal form. If successful, these investigations will lead to safe and effective methods to prevent prion infections as well as therapies that work in either the pre-symptomatic or symptomatic phases of disease.

Diagnostics

Improved diagnostic tests for TSE diseases are critical for the success of both therapeutic strategies and eradication programs. NIAID scientists are exploring various approaches to creating new tests. In addition, NIAID has provided funds to the CDC for better monitoring of TSE disease incidence and to improve collection of tissue specimens for TSE disease-related diagnostics.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.