Nano-QuIC Diagnostic Test Could Prove Useful for Detecting Protein-Misfolding Diseases
University of Minnesota Twin Cities researchers have developed a groundbreaking new diagnostic technique that will enable faster and more accurate detection of neurodegenerative diseases. This method is likely to open the door to early treatment and mitigation of many diseases that affect humans, such as Alzheimer’s and Parkinson’s, and similar diseases that affect animals, such as chronic wasting disease (CWD).
Their new study was published in Nano Lettersleading journal in the field of nanotechnology published by the American Chemical Society.
“This paper primarily focuses on chronic wasting disease in deer, but ultimately our goal is to extend the technology to a broad spectrum of neurodegenerative diseases, Alzheimer’s and Parkinson’s being the two main targets,” said Sang-Hyun Oh, co-senior author of the paper and Distinguished McKnight University Professor in the University of Minnesota’s Department of Electrical and Computer Engineering. “Our vision is to develop highly sensitive and robust diagnostic techniques for various neurodegenerative diseases so that we can detect biomarkers early, perhaps allowing more time for the deployment of therapeutic agents that can slow disease progression. We want to help improve the lives of millions of people affected by neurodegenerative diseases.”
Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, mad cow disease, and CWD (found in many deer) share a common feature- the accumulation of misfolded proteins in the central nervous system. Detecting these misfolded proteins is critical to understanding and diagnosing this devastating disorder. However, existing diagnostic methods, such as enzyme-linked immunosorbent and immunohistochemical assays, can be expensive, time consuming, and limit the specificity of antibodies.
The University of Minnesota researchers’ method, dubbed Nano-QuIC (Nanoarticle-enhanced Quaking-Induced Conversion), significantly improves the performance of advanced protein misfolding detection methods, such as NIH Rocky Mountain Laboratories Real-Time Earthquake Induced Conversion (RT-QuIC test).
The RT-QuIC method involves churning a normal protein mixture with a small amount of misfolded protein, triggering a chain reaction that causes the protein to double and allows the detection of these disordered proteins. Using tissue samples from deer, the University of Minnesota team showed that adding 50 nanometer silica nanoparticles to the RT-QuIC experiment dramatically reduced detection time from about 14 hours to just four hours and increased sensitivity by a factor of 10.
Typically a 14-hour detection cycle means lab technicians can only run one test per normal work day. However, with a detection time of less than four hours, researchers can now run three or even four tests per day.
Having faster and more accurate detection methods is critical to understanding and controlling the transmission of CWD, a disease that is spreading in deer across North America, Scandinavia and South Korea. The researchers believe that Nano-QuIC may eventually prove useful for detecting protein folding diseases in humans, particularly Parkinson’s, Creutzfeldt-Jakob Disease, Alzheimer’s, and ALS.
“Testing these neurodegenerative diseases in animals and humans has been a major challenge for our society,” said Peter Larsen, co-senior author of the paper and assistant professor in the University of Minnesota’s Department of Veterinary and Biomedical Sciences. “What we’re seeing now is a very exciting time when new next-generation diagnostic tests emerge for this disease. The impact of our research is that it greatly improves next-generation tests, makes them more sensitive, and it makes them more accessible.”
This research was funded by the Minnesota Environment and Natural Resources Trust Fund as recommended by the Citizens-Legislative Commission on the Resources of Minnesota (LCCMR); the Minnesota Rapid Agricultural Response Fund Agricultural Experiment Station; and the Minnesota Agriculture, Research, Education, Extension and Technology Transfer (AGREETT) program.
“Minnesotans value science and support basic and applied research. As legislators, we have invested Environmental Trust Fund funds to provide solutions to complex problems such as chronic wasting disease,” said Representative Rick Hansen, chair of the Minnesota Home Environment and Natural Resources Committee and co-chair of the LCCMR. “I am proud of the work of the LCCMR and the legislature in supporting this research and will continue to advocate for funding for research and preventing future problems affecting our wildlife and ourselves.”
Larsen and Oh led the university’s Minnesota Center for Prion Research and Outreach (MNPRO) molecular diagnostics research and development team, which leveraged this government funding to conduct research on a protein folding disease that has had a major impact on the state of Minnesota.
In addition to Oh and Larsen, the team involved in the paper includes University of Minnesota Twin Cities researchers Peter Christenson (lead author and Ph.D. candidate in the Department of Electrical and Computer Engineering), Manci Li (Ph.D. candidate in the Program of Comparative Biosciences and Molecular), and Gage Rowden (researcher in the Department of Veterinary and Biomedical Sciences).