Kuru Disease Mutations and Brain Diseases

Members of the Fore tribe who live in the highlands of Papua New Guinea appear to have developed a strong genetic resistance to a degenerative and fatal brain disease known as Kuru.

The disease reached epidemic proportions in the 1950s amongst tribe's people and was linked to their cannibalistic ritual of eating the brain tissue of the recently departed. Kuru devastated populations and exhaustive research by American physician Daniel Gajdusek discovered that it was caused by infectious agents, later known as prions. When the cannibalistic practice was stopped the incidence of Kuru tapered off.

Kuru is a prion disease and is related to mad cow disease (BSE) in cattle and Creutzfeldt-Jacob disease (CJD) in humans.

Although Kuru was killing off people in great numbers there were survivors of this mid-20th Century epidemic, and it appears that the reason for this is that they developed a gene variant which conferred resistance to the disease.

Scientists from the Medical Research Council's Prion Unit in the UK studied the DNA of more than 3,000 survivors of the epidemic, and compared this with the DNA from victims of the disease. In some of the survivors they found a variation in the PRNP gene which makes prions.

The variant occurs at a position known as codon 127 which usually contains the glycine amino acid. However, they discovered that in the DNA of some survivors and their descendants glycine had been replaced by another amino acid - valine. The variant is now known as G127V. None of the 152 victims had the variant suggesting that it confers high or complete resistance to Kuru. Experts believe that this is a compelling example of natural selection in humans.

"The fact that this genetic evolution has happened in a matter of decades is remarkable," said Prof John Collinge, director of the Prion Unit on the BBC's Today programme. "This community of people have developed their own biologically unique response to a truly terrible epidemic. It's absolutely fascinating to see Darwinian principles at work here."

The research into this kuru mutation is fascinating on two levels. The first is that it is a speeded up example of natural selection. Kuru was killing about 2% of the tribe population a year, with mortality particularly high in women and young children. In fact in some villages there were no adult women left. So when a genetic mutation occurred that offered resistance it was very rapidly selected over the space of a few generations.

Secondly, the findings could help scientists to understand more fully how the disease mechanisms operate in Kuru and other brain diseases. They already know that Kuru is caused by a prion protein changing shape into a rogue form that accumulates and damages the brain. So finding out how the G127V gene variant confers resistance will provide a new target for the development of drugs to target prions and stop them from going rogue. Researchers from the Prion Unit think they may have evidence that the prion protein produced by the gene variant may stop abnormal prion proteins from spreading. Though they do not know for sure.

There could also be a wider benefit to other brain diseases such as Alzheimer's and Parkinson's from this research, because the same general genetic mechanisms seem to underpin them all.