Increasing evidence points to an association between bowel and Parkinson's. New research from the Faculty of Medicine at Johns Hopkins University has tightened the context and presented a new model for drug testing for the treatment of neurodegenerative disorder.
In mouse studies, Johns Hopkins scientists found that alpha-synuclein protein is misfolded – which, according to scientists, accumulates in the brain and drives Parkinson's disease – can migrate from the gut to the brain. They published the results in the journal Neuron.
As early as 2003, the German neuroanatom Heiko Braak and colleagues found that in postmortem samples of Parkinson's patients also clots of alpha-synuclein occur in the nervous system, which controls the intestinal enteric nervous system. This made sense to them since Parkinson's patients often develop gastrointestinal discomforts such as constipation long before they have motor impairments that are characteristic of Parkinson's disease. Braak suspected that Parkinson's is from the gut.
But there was a big question: are these alpha-synuclein deposits in the enteric nervous system identical to those in the brain? In other words, do the aggregates actually travel? To answer this, Johns Hopkins neurologist Ted Dawson and colleagues injected synthetic misfolded alpha-synuclein into the intestines of dozens of healthy mice.
Dawson's team examined the brain tissues of the animals one, three, seven, and ten months after the injection, and found that the protein near the vagus nerve, which is the main organ of the vagus nerve Brain connects, accumulated to the intestine and carried on to the brain. The observation is in line with what a Lund University team described in a 2014 study in the journal Acta Neuropathologica.
After cutting the vagus nerve in a group of mice, the animals showed no signs of cell death that were observed. In patients with intact vagus nerves, the team said in a press release.
But how does that translate into behavioral changes related to Parkinson's? The researchers answered this question by commissioning the mice with nest building and exploration of new environments.
Mice with the misfolded alpha-synuclein and intact indistinct nerves used far fewer nesting material than the control mice and those with severed blunt nerves, and their nests were smaller and more disordered according to the team. Motor control of animals worsened with progressive disease, much as Parkinson's develops in humans, said Han Seok Ko, a co-author of the study, in a statement.
In another test, the researchers placed the mice in a large open field to see how they reacted to a new environment. The healthy mice and those who had their vagus nerves removed explored the center of the box for about 20 to 30 minutes while the others spent less than five minutes approaching protected borders. This suggests that mice that received alpha-synuclein and had intact vagus nerves were more anxious, a symptom consistent with Parkinson's, the researchers said.
The demonstration of the possible role of the intestine in neurological disorders is the basis of several biotech startups. These include Axial Biotherapeutics, which recently spent $ 25 million funding its Parkinson's and autism programs on gut microbiota. New York-based Kallyope also uses the gut-brain axis to find small molecules for metabolic and neurological disorders.
Targeting alpha-synuclein is also a popular strategy in Parkinson's research. AbbVie and Voyager Therapeutics have recently expanded their partnership to use "vectorized" antibodies against the toxic protein clot. A team from Georgetown University found that the blood cancer drug Tasigna from Novartis may be effective in Parkinson's disease after it has shown that the drug can reduce alpha-synuclein lumps and increase brain dopamine levels in Parkinson's patients.
A team last fall A group of scientists led by the Van Andel Research Institute found that people whose attachments were removed at the beginning of their lives were less likely to develop Parkinson's. They also discovered alpha-synuclein clots in the cecal tissue that they examined.
Dawson's Johns Hopkins team had previously identified a protein called c-Abl as a putative driver for Parkinson's alpha-synuclein lumps.
Dawson hopes his team will do this The latest discovery may provide a model for the study of Parkinson's progression. The researchers are now planning to investigate which parts of the vagus nerve allow the misfolded protein to get to the brain and to investigate possible mechanisms to stop it. All in all, the new evidence of a connection between the gut and brain is "a target for early intervention in the disease," he said.