Scientists have linked a serious neurodegenerative disorder to a newly discovered type of prion related to the one that causes mad cow disease.
Multiple System Atrophy (MSA) has similarities to Parkinson's disease, and this new research suggests it is caused by prions related to the misfolded proteins involved in other incurable diseases such as Creutzfeldt-Jakob Disease (CJD), the University of California, San Francisco reported.
These new findings could lead to a treatment for MSA and also point out the risks imposed on medical staff who handle MSA-infected tissue. The recent findings also mark the first discovery of a human disease caused by a new prion in the past five decades.
In 1982, UCSF's Stanley Prusiner determined that the cause of scrapie (a disease seen in sheep) was linked to an "infectious protein," or prion. Later, he determined the same prion protein caused bovine spongiform encephalopathy (BSE) and CJD, more commonly known as "mad cow disease," in both humans and cattle. This new research shows that infectious proteins can also be the source of other neurodegenerative illnesses.
"Now we've conclusively shown that a new type of prion causes MSA," said UCSF's Kurt Giles, associate professor of neurology, IND researcher and senior author on the second of the two new studies. "This is our mark in the sand."
The original prion protein (PrP) linked to CJD is believed to exist in two forms: one innocuous and the other fatal. When PrP prions are fatal, they misfold and latch onto other PrP molecules, causing them to lose their shape and form plaques in the brain.
To make their findings, the researchers looked at samples of brain tissue from two human MSA patients and were able to transmit the disease to a mouse model for Parkinson's diseas, expressing a mutant human alpha-synuclein gene. To confirm these findings, the team expanded the study to include tissue samples from a dozen more MSA victims from various parts of the world. When mice were exposed to this tissue, they still developed neurodegeneration. They also found that the brains of infected mice contained abnormally high levels of insoluble human alpha-synuclein, and the disease could most likely be transmitted between mice. These findings bring up a serious new health concern.
"You can't kill a protein," Giles said. "And it can stick tightly to stainless steel, even when the surgical instrument is cleaned. We're advocating a precautionary approach. People are living longer and likely getting more brain surgeries. There could be undiagnosed neurodegenerative diseases that - if they're caused by prions - mean infection could be a real worry."
Using a rapid new testing method prion transmission using human cell cultures, the researchers demonstrated it only takes four days for human MSA tissue to infect cultured cells with alpha-synuclein mutations. This is significantly less time than the 120 days it takes for the disease to spread to a mouse model.
"The challenge of studying neurodegeneration is that it's a disease of aging," said post-doctoral researcher Amanda Woerman. "You have to let the mouse models develop for such a long time that research on cures is really slow to progress. Now, with these cell models, we can test how to inactivate alpha-synuclein aggregates at a speed that just wouldn't be feasible in animals."
The findings were published in a recent edition of the journal Proceedings of the National Academy of Sciences.
