‘Cannibal disease’ study reveals gene that produces CJD resistance

15 Jun

Researchers studying a neurological disease associated with cannibalism have discovered a natural genetic variation that produces resistance to brain diseases such as Creutzfeldt-Jakob disease and bovine spongiform encephalopathy, also known as “mad cow disease.”

MRI scans of the brain.
Creutzfeldt-Jakob disease is a rare neurodegenerative disease and one cause of dementia.

Their discovery could be the first step toward understanding how neurodegenerative disorders such as Creutzfeldt-Jakob disease (CJD) and others dementias could be prevented and treated.

The study, published in Nature, was conducted by researchers from the UK Medical Research Council’s (MRC) Prion Unit at University College London (UCL) in the UK.

Prions are infectious proteins that can cause lethal neurodegenerative diseases. In addition to causing diseases such as CJD and mad cow disease (BSE), prions are also a rare cause of dementia.

These proteins damage the brain by changing shape and forming misshapen chains. This process has also been identified in Parkinson’s disease and common forms of dementia such as Alzheimer’s disease.

One disease caused by prions that has been studied at the MRC’s Prion Unit is kuru, a rare disease that was typically found in a remote region of Papua New Guinea, among a community that consumed the brains of their dead as part of a funeral ritual.

In the late 1950s, at the height of a kuru epidemic, up to 2% of the population was killed by the disease each year. The mortuary feasts of the Fore people stopped in 1960, yet cases of the disease were reported in subsequent years, indicating that kuru has a long incubation period. It is now believed that the average incubation period for kuru is 10-13 years.

Experts believe that those who survived exposure to kuru may have a genetic resistance to the disease, and that the identification of any genetic changes that may have occurred could provide insight into how similar diseases such as CJD could be prevented or treated.

‘A striking example of Darwinian evolution in humans’

Working alongside colleagues at the Papua New Guinea Institute, the researchers discovered a specific gene – the prion protein gene – carried by some of the survivors of kuru that they believed might confer protection from the disease.

To investigate, the team bred mice with the same genetic change as that found in the kuru survivors. They achieved this by altering one of the amino acids that the prion protein is comprised of. The researchers then exposed the mice to kuru and CJD to test for resistance.

The team discovered that the mice were completely resistant not only to kuru but all forms of CJD too, including a form caused by human infection with BSE.

“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,” says study leader Dr. Emmanuel Asante. “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.”

The researchers believe that if they can work out how this change to the prion protein structure prevents it from changing shape and forming damaging chains, they may be able to discover a way to prevent CJD and other dementias caused by these chains of misshapen proteins.

“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,” states Prof. John Collinge, leader of the kuru research program.

“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.”

Last year, Medical News Today reported on a study suggesting that there could be a way to harness the brain’s capacity to self-repair and preserve brain function in brain-wasting prion diseases.

Written by James McIntosh