SASKATOON – Even Dr. Scott Napper (PhD) uses words like terrifying when describing the focus of his research—a group of diseases caused when otherwise harmless proteins go awry, creating conditions that are invariably fatal and currently untreatable. “But that’s what I love about it — it’s so interesting and so very important,” said Napper, a scientist with the Vaccine and Infectious Diseases Organization (VIDO) at the University of Saskatchewan (USask). Napper has a leading role in the search for vaccines to treat diseases caused by misfolded proteins. His initial research focused on prion diseases, which include mad cow disease, scrapie in sheep, and chronic disease (CWD) in deer and elk. However, several similar neurodegenerative diseases in humans are also on his radar, including Alzheimer’s, Huntington’s, Parkinson’s, and amyotrophic lateral sclerosis (Lou Gehrig’s disease). “Is CWD the priority? Yes. Is Alzheimer’s the priority? Yes. We are doing this work on human and animal vaccines in parallel,” he said. Napper explained that these diseases arise when a protein misfolds and acquires new and destructive characteristics. And once it is misfolded, the new protein becomes self-replicating. When the misfolder comes into contact with a correctly folded version of itself, that protein also misfolds, “so one becomes two and two becomes four, and you get a cascade of misfolding that results in fatal disease.” Prion diseases began to attract attention in the early 1950s with the discovery of Kuru, a neurodegenerative disease found in the Fore populations of Papua New Guinea, Napper said. It was associated with burial cannibalism – the people of For cooked and ate their dead family members, thereby spreading the disease. When the cause of Kuru was identified about 20 years later as a proteinaceous infectious particle, or prion, “it was unbelievable,” Napper said. “It completely changed the way we think about infectious diseases, because it’s not about a bacterium or a virus.” This prion-like mechanism is now known to be responsible for other human neurodegenerative diseases such as Alzheimer’s. And the search for a cure has recently gained momentum. The Alberta Conservation Association, in partnership with Alberta Environment and Parks, and the Saskatchewan Ministry of Environment, has provided $1.2 million to fund research into an oral vaccine to manage CWD, which poses a significant risk to wild populations in four provinces and 28 states. A team of scientists at four universities in western Canada, including Napper, Dr. Philip Griebel (DVM, PhD) and Dr. Suresh Tikoo (DVM, PhD) at VIDO, as well as Dr. Sidney Hayes (PhD) in the College of Medicine, aim to develop oral CWD vaccines that can be released into affected habitats. The other researchers are from the Universities of British Columbia, Alberta and Calgary. Scientists will work with wildlife groups to develop and deliver an effective real-world solution. “We’re dressed in the lab and they’re in shape, but we can all work together,” Napper said. On the human front, the Weston Family Foundation through the Weston Brain Institute is providing $1.2 million to Napper and three research colleagues at other Canadian universities to develop a vaccine for misfolded protein diseases in humans. Building on previous developments, scientists will create antibodies that attach to misfolded proteins – one already selected for preclinical development – to prevent the development of diseases. In both cases, Napper appreciates the team approach. “Just as we saw with COVID when the global scientific community came together to develop a vaccine, we are better, stronger and smarter if we work together and leave our self-interest and selfishness at the door.” That doesn’t mean the job will be easy, but early results are highly encouraging, Napper said. “The pipeline is there and once we have the target protein, we were able to get the required types of immune responses. All the diseases we’ve talked about have a different target protein, but vaccine development all uses similar processes.” Napper, who is also a professor of biochemistry at the USask College of Medicine, believes VIDO’s unique culture and expertise will make it a significant contributor. Created in 1975 to focus on infectious diseases in Canada’s livestock industry, VIDO has expanded its mission to include research and development of vaccines related to human diseases, with COVID-19 being an example. The breadth of talent among VIDO scientists means the agency “can take a team approach to complex problems,” he said. “I’m not an immunologist, but the guy in the next office is, and there’s a scientist who’s been developing oral vaccines for 20 years just one floor down. We all want to make the world a better place.” Napper admitted that it is quicker to develop and market a vaccine for animals than for humans, “so it is not unreasonable to imagine a CWD vaccine in seven to 10 years.” A human vaccine will take longer, but Napper isn’t daunted. “Our initial success may just be slowing down the progression of diseases, but we will gradually get successes as they come. There’s hope.” — Submitted by USask Media Relations
