Scientists just created a deadly human brain protein in a lab for the first time

Brain-wasting diseases are a terrifying prospect, made all the more distressing because of the lack of effective treatments currently available. While we know that such disorders, like Creutzfeldt-Jakob disease (CJD), are caused by infectious proteins called prions, experts have struggled to truly decode and study these proteins – until now.

Scientists from Case Western Reserve University School of Medicine (CWRU) have synthesised the world’s first artificial human brain prion in a lab. Although this sounds like the opening scene of a zombie film, it is actually intended, and vital, to help us better understand the workings of how these deadly, infectious proteins develop and spread.  

“This accomplishment represents a watershed,” said Jiri G. Safar, the study’s lead author. “Until now our understanding of prions in the brain has been limited. Being able to generate synthetic human prions in a test tube, as we have done, will enable us to achieve a much richer understanding of prion structure and replication.

“This is crucial for developing inhibitors of their replication and propagation throughout the brain, which is essential for halting prion-based brain disease.”

In other words: the more we can understand prions, the closer we get to developing treatments to stop them. What we already know is that prions are proteins that have folded incorrectly, and can create a domino effect by binding to neighbouring proteins, making microscopic holes in the tissues and effectively turning the brain into a mushy sponge.  

In findings published in Nature Communications, the scientists claim to have discovered an essential contributory cause of the disease – a process known as Ganglioside GM1, which plays a role in triggering the replication of prions. They also pinpointed a reason for the infection of prions to an area on the molecule’s structure known as the C terminal domain.

“Our findings explain, at the structural level, the emergence of new human prions and provide a basis for understanding how seemingly subtle differences in mis-folded protein structure and modifications affect their transmissibility, cellular targeting, and thus manifestation in humans,” said Safar.

Non-human prions have previously been synthesised, with studies carried out on mice and hamsters, but the research from CWRU is the first to involve a “highly destructive” artificial human prion, made from a genetically engineered human prion protein expressed in E. coli bacteria.

The results of the study could create ripples in how we consider degenerative disorders. Because Parkinson’s and Alzheimer’s spread through the brain in a similar fashion to CJD, the hope is that understanding prions could lead to better treatments for these diseases, as well.