The USask-led research team aims to develop vaccines for prion diseases.
SASKATOON – Even Dr. Scott Napper (PhD) uses words like fear when describing the focus of his research: a group of diseases caused when harmless proteins go rogue, creating conditions that are always fatal and currently untreatable treat.
“But that’s what I love about it: it’s so interesting and so important,” said Napper, a scientist at the Vaccine and Infectious Disease Organization (VIDO) at the University of Saskatchewan (USask).
Napper plays a leading role in the search for vaccines to treat diseases caused by misfolded proteins. His original research focused on prion diseases, including mad cow disease, scrapie in sheep, and chronic wasting disease (CWD) in deer and elk.
However, several similar neurodegenerative diseases in humans are also on their 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 do this work on both human and animal vaccines in parallel,” he said.
Napper explained that these diseases occur when a protein misfolds and takes on devastating new characteristics. And once misfolded, the new protein becomes self-propagating.
When the misfold 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 ends up in a deadly disease.”
Prion diseases first gained attention in the early 1950s with the discovery of Kuru, a neurodegenerative disease found in the Fore people of Papua New Guinea, Napper said. It was related to funerary cannibalism: the Fore cooked and ate their deceased family members, thereby spreading the disease.
When the cause of Kuru was identified about 20 years later as an infectious protein particle, or prion, “it was mind-blowing,” Napper said. “It completely changed the way we think about infectious diseases because it’s not about a bacteria 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 recently got a boost.
The Alberta Conservation Association, in partnership with Alberta Environment and Parks and the Saskatchewan Ministry of Environment, has contributed $1.2 million to fund research into an oral vaccine to manage CWD, which poses a significant risk for wild populations in four provinces and 28 states.
A team of scientists from four western Canadian universities, including Napper, Dr. Philip Griebel (DVM, PhD) and Dr. Suresh Tikoo (DVM, PhD) at VIDO, as well as Dr. Sidney Hayes (PhD) in the School of Medicine, aim to develop oral vaccines for CWD that can be released into affected habitats. The other researchers are from the universities of British Columbia, Alberta and Calgary.
Scientists will work in partnership with wildlife groups to develop and deliver an effective real-world solution.
“We’re in lab coats and they’re in camouflage, 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 from other Canadian universities to develop a vaccine against misfolded protein diseases in humans Building on previous developments, scientists will generate antibodies that bind to misfolded proteins (one has already been selected for preclinical development) to prevent disease development.
In both cases, Napper appreciates the team’s approach.
“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 egos and self-interest at the door.”
That doesn’t mean the work will be easy, but the early results are very encouraging, Napper said. “The pipeline is there, and once we have the target protein, we’ve been able to get the kinds of immune responses that are needed. Every disease we’ve talked about has a different target protein, but vaccine development 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 him an important collaborator.
Created in 1975 to focus on infectious diseases in Canada’s livestock industry, VIDO expanded its mission to include research and development of vaccines related to human diseases, with COVID-19 as an example. The breadth of talent among VIDO scientists means the organization “can take a team approach to complex problems,” he said.
“I’m not an immunologist, but the guy in the office next door 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’s faster to develop and commercialize a vaccine for animals than for humans, “so it’s not unreasonable to imagine a CWD vaccine in seven or ten years.” A human vaccine will take longer, but Napper is undeterred.
“Our initial success might simply be slowing disease progression, but we will have incremental successes as they emerge. There is hope.”
— Presented by USask media relations