Conference Coverage

MS may be a transmissible protein misfolding disorder, study suggests

 

Key clinical point: Translational research suggests the primary damage in MS may be caused by transmissible protein misfolding.

Major finding: Transgenic mice over-expressing human prion protein that were injected with brain matter from MS patients developed various levels of significant pathology, and brain homogenate from these mice could transmit illness to naive transgenic mice.

Study details: Transgenic mice over-expressing human prion protein received intracerebral injection of brain homogenate from patients with primary or secondary-progressive MS

Disclosures: The authors have no disclosures with the exception of one who disclosed serving as deputy editor of the Multiple Sclerosis Journal. Funding sources include Canada Research Chairs, Alberta Innovates-Health Solutions, and the Alberta Prion Research Institute.

Source: Tsutsui S et al. ACTRIMS Forum 2018 Abstract LB282.


 

REPORTING FROM ACTRIMS FORUM 2018

Multiple sclerosis appears to be a transmissible protein misfolding disorder like Alzheimer’s and Parkinson’s diseases, results of a new study suggest. MS may even be caused by prions, potentially putting it into the same category as Creutzfeldt-Jakob disease.

Researchers don’t think MS is contagious between humans. But their findings in mice do suggest that the disease is transmissible from “a seed of protein misfolding,” Shigeki Tsutsui, DVM, PhD, of the University of Calgary (Alta.), said in an interview in advance of his presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Dr. Shigeki Tsutsui, research assistant professor in clinical neuroscience at the University of Calgary, Alberta

Dr. Shigeki Tsutsui

According to Dr. Tsutsui, the study is rooted in the MS origin theory that some factor causes damage in the central nervous system and triggers a secondary autoimmune response that sparks the disease.

“The next question is: ‘What is actually causing primary damage?’ ” he said. “Our hypothesis is that it’s protein misfolding. If protein misfolding targets the central neuron cells, then those damaged cells release a kind of a trigger to start an immune response.”

This isn’t an unusual concept. Protein misfolding is believed to cause several chronic neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis, Dr. Tsutsui said.

The researchers focused on the potential transmissibility of human prion protein “since we thought that the prion protein might be the candidate causing the MS,” he said.

Prion diseases are extremely rare and often deadly. They appear when normal cellular prion proteins are induced to misfold when they come in contact with infectious agents known as prions.


In humans, prion diseases include Creutzfeldt-Jakob disease, fatal familial insomnia, and kuru (a condition spread among cannibals who eat the brains of other humans). Most famously, a variant of Creutzfeldt-Jakob disease has been linked – but not conclusively – to the eating of meat from cows infected with mad cow disease.

Depending on the condition, prion diseases can appear spontaneously, via inheritance or through infection.

In the new study, researchers intracerebrally injected brain homogenate from 10 patients with primary or secondary-progressive MS into 36 transgenic mice. All the mice over-expressed human prion protein. A control group of 23 mice were injected with homogenate from six donor brains.

At 6-12 months, the control mice did not develop pathology. However, the mice injected with brain matter from MS patients developed various levels of significant pathology. The researchers also managed to transmit illness from affected mice into another group of transgenic mice that over-expressed human prion protein via injection of brain homogenate.

While the mice in the study represent “a very extreme case” since their levels of prion protein expression were very high, it’s clear that “MS is actually transmissible,” Dr. Tsutsui said.

The study authors speculate that pathogenic prion protein triggers an autoimmune response by degenerating myelin and causing the release of cellular debris.

Could MS also be contagious? It may not be, even if it’s a prion disease, Dr. Tsutsui said. Some prion disease variants are neither contagious nor infectious.

The researchers plan to study the animal model they’ve created and explore the potential for its use in research, Dr. Tsutsui said.

The authors have no disclosures with the exception of one who disclosed serving as deputy editor of the Multiple Sclerosis Journal. Funding sources include Canada Research Chairs, Alberta Innovates-Health Solutions, and the Alberta Prion Research Institute.

SOURCE: Tsutsui S et al. ACTRIMS Forum 2018 Abstract LB282.

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