Scientists have identified a naturally-occurring variant of the human prion protein that can protect against deadly diseases such as Creutzfeldt-Jakob disease (CJD), and may have developed because of human cannibalism.
Infectious agents, called prions, cause fatal brain diseases, University College London reported. These infections are rare, but the process that occurs in the disease development is very similar to what is seen in Alzheimer's, Parkinson's and other neurodegenerative diseases.
Researchers have long been studying a disease called kuru, which once devastated populations in remote areas of the Papua New Guinea highlands. The disease is caused by the same strains of prions that are associated with CJD. Kuru was found to be prevalent in a community called the Fore that used to consume their dead as a sign of respect. This practice was banned, and the last mortuary feast is believed to have occurred in the late 1950s. The epidemic reached its height at about the same time as the final feast, and caused the death of about 2 percent of the population annually. Researchers believed members of this population were particularly resistant to kuru due to genetic changes, which could help reveal ways to treat CJD.
A team of researchers pinpointed the prion protein gene in kuru survivors that appeared to protect them against the disease, which would be an example of human evolution. They bred genetically engineered mice that had the same genetic change, which required the alteration of only on of the 253 building blocks or amino acids that make up the prion protein. They observed these mice were 100 percent were resistant to kuru. CJD, and mad cow disease (another prion disease).
"From the human genetic work the Unit has carried out in Papua New Guinea we were expecting the mice to show some resistance to disease. However, we were surprised that the mice were completely protected from all human prion strains. The result could not have been clearer or more dramatic," said researcher Emmanuel Asante.
In the past, researchers believed the Fore most likely would have been wiped out of cannibalism had not been outlawed, but these new findings suggest instead the region would have been repopulated with people who were resistant to the disease. In the future, researchers hope to better understand how the simple change in the prion protein prevents it from changing shape and becoming an infectious prion.
"This is a striking example of Darwinian evolution in humans - the epidemic of prion disease selecting a single genetic change that provided complete protection against an invariably fatal dementia. Much work is now ongoing in the MRC Unit to understand the molecular basis of this effect which we expect to provide key insights into how seeds of other misshapen proteins develop in the brain and cause the common forms of dementia, thereby guiding us to new treatments in the years ahead," said Professor John Collinge, the Unit Director, who leads the kuru research program.
The findings were published in a recent edition of the journal Nature.
