Prion Protein Fibrils

Prion Protein Fibrils.

There is a lot scientists don’t know about the diseases created when a prion — an infectious protein blamed for causing fatal neurological diseases — goes bad.

A recently completed study at the Rocky Mountain Laboratory in Hamilton showed the infectious agent that can cause a variety of fatal diseases is both incredibly hardy and has the ability to be transmitted from one host to another.

Prion diseases originate when normally harmless prion protein molecules mutate and begin to fold in irregular patterns. The clusters and filaments that form in the brain result in a condition that’s not treatable and is always fatal.

No one is certain exactly why that happens.

Montanans took note this past year of prion-based diseases when Chronic Wasting Disease was discovered in deer herds in eastern Montana. While the neurological disease is always fatal to members of the deer family, including elk, there have been no documented cases of it infecting humans.

A similar prion-based disease did make the leap from one species to another in the 1990s when Great Britain’s Mad Cow epidemic nearly collapsed that country’s livestock industry and killed more than 200 people in England and Western Europe.

The recent study by researchers with the National Institute of Allergy and Infectious Disease’s lab in Hamilton found that a form of the disease passed genetically within families could be spread to others.

Their study focused on brain samples taken from three people who died from the very rare familial human prion disease.

Dr. Bruce Chesebro, chief of the NIAID Laboratory of Persistent Viral Diseases, led the study that looked at whether the three different prion protein mutations that form the disease were transmissible.

After observing mice infected with the prion for about two years, the scientists found two of three mutations could be spread.

Beyond that, the study also showed the resiliency of prions.

One of the samples was initially preserved in formaldehyde for three days, then embedded in wax before being dried on glass specimen slides for several years and then was re-hydrated for the study.

“Going through all those steps to fix the tissue didn’t kill the agent,” Chesebro said. “It wasn’t enough to sterilize it or make the tissue safe to handle. It may have killed 99 percent of the agent, but there was still enough left to infect the mice.”

The sample infected four of the eight mice exposed to it.

That finding, Chesebro said, illustrates the hardiness of prion infectiousness and the potential risks associated with prion transmission through surgery, blood transfusions or tissue donations.

If infectious prions could survive that long in a sterile environment, it's easier to understand how they might remain viable in the soil long enough to impact cervids like deer and elk that are susceptible to Chronic Wasting Disease.

“If animals graze right down to the earth, it can spread through the soil,” Chesebro said. “That’s been demonstrated before.”

Scientists know of 34 mutations associated with familial human prion diseases. So far, nine of the 13 tested were shown to be transmissible to either monkeys or mice.

While people infected with the sporadic version of human prion diseases will typically get sick between six to 12 months and often die within a year, Chesebro said people with the genetic type can live up to 25 years after the disease is detected.

“But it’s not like clockwork,” he said. “Some mutations impact families in different ways. It’s not really clear why. There's still a lot that we don't know."