A Role for Inflammation? Yet another idea holds t
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Posted On: 08/22/2020 3:54:03 AM
A Role for Inflammation?
Yet another idea holds that that intestinal inflammation, possibly from gut microbes, could give rise to Parkinson’s disease. The latest evidence supporting this idea comes from a large epidemiological study, in which Inga Peter, a genetic epidemiologist at the Icahn School of Medicine at Mount Sinai, and her colleagues scanned through two large U.S. medical databases to investigate the overlap between inflammatory bowel diseases and Parkinson’s.
Their analysis compared 144,018 individuals with Crohn’s or ulcerative colitis and 720,090 healthy controls. It revealed that the prevalence of Parkinson’s was 28 percent higher in individuals with the inflammatory bowel diseases than in those in the control group, supporting prior findings from the same researchers that the two disorders share genetic links. In addition, the research team discovered that in people who received drugs used to reduce inflammation—tumor necrosis factor (TNF) inhibitors—the incidence of the neurodegenerative disease dropped 78 percent.
This study further validates the theory that gut inflammation could drive Parkinson’s pathogenesis, says Madelyn Houser, a graduate student in neuroscientist Malú Tansey’s lab at Emory University. The anti-TNF finding in particular, she adds, suggests that the “overlap between the two diseases might be primarily mediated by inflammation.”
Intestinal inflammation might give rise to Parkinson’s in several ways, Houser explains. One possibility is that a chronically inflamed gut might elevate alpha-synuclein levels locally—as Zasloff’s investigation in children suggests—or else it may give rise to inflammation throughout the body, which in itself could increase the permeability of the gut and blood-brain barriers. Or else it could increase circulating cytokines, molecules that that can promote inflammation. Tansey adds that changes in the microbiome could also be influencing gut inflammation.
“There’s probably multiple pathways that lead the gut to the brain,” Peter says, explaining that it is too early to rule out any hypotheses. For now, her team is focused on determining whether the protective effect of anti-TNF compounds is due to the lowering of inflammation throughout the body, which could result from other conditions, or whether they only benefit individuals with bowel disorders. Peter plans to investigate the prevalence of Parkinson’s in other patients who take these drugs, such as those with psoriasis or rheumatoid arthritis.
Because not all Parkinson’s patients will have inflammatory bowel disorders, findings from the investigations into the co-occurrence of the two conditions might not generalize to everyone with the neurodegenerative disease, Mazmanian says. Still, these studies and many others that have emerged in recent years support the idea that the gut is involved in Parkinson’s is correct, he adds. “If this is indeed true, it allows us to now devise interventions that target the gut instead of the brain.”
Already, some researchers have started to test such interventions. In 2015, Zasloff and his colleagues launched a company, Enterin, that is currently testing a compound that slows alpha-synuclein aggregation in the gut. Although the treatment is intended to reduce non-motor symptoms of Parkinson’s, such as constipation, the researchers hope that by targeting early gut pathology, they will be able to restore—or prevent—the disease’s effects on the central nervous system.
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Yet another idea holds that that intestinal inflammation, possibly from gut microbes, could give rise to Parkinson’s disease. The latest evidence supporting this idea comes from a large epidemiological study, in which Inga Peter, a genetic epidemiologist at the Icahn School of Medicine at Mount Sinai, and her colleagues scanned through two large U.S. medical databases to investigate the overlap between inflammatory bowel diseases and Parkinson’s.
Their analysis compared 144,018 individuals with Crohn’s or ulcerative colitis and 720,090 healthy controls. It revealed that the prevalence of Parkinson’s was 28 percent higher in individuals with the inflammatory bowel diseases than in those in the control group, supporting prior findings from the same researchers that the two disorders share genetic links. In addition, the research team discovered that in people who received drugs used to reduce inflammation—tumor necrosis factor (TNF) inhibitors—the incidence of the neurodegenerative disease dropped 78 percent.
This study further validates the theory that gut inflammation could drive Parkinson’s pathogenesis, says Madelyn Houser, a graduate student in neuroscientist Malú Tansey’s lab at Emory University. The anti-TNF finding in particular, she adds, suggests that the “overlap between the two diseases might be primarily mediated by inflammation.”
Intestinal inflammation might give rise to Parkinson’s in several ways, Houser explains. One possibility is that a chronically inflamed gut might elevate alpha-synuclein levels locally—as Zasloff’s investigation in children suggests—or else it may give rise to inflammation throughout the body, which in itself could increase the permeability of the gut and blood-brain barriers. Or else it could increase circulating cytokines, molecules that that can promote inflammation. Tansey adds that changes in the microbiome could also be influencing gut inflammation.
“There’s probably multiple pathways that lead the gut to the brain,” Peter says, explaining that it is too early to rule out any hypotheses. For now, her team is focused on determining whether the protective effect of anti-TNF compounds is due to the lowering of inflammation throughout the body, which could result from other conditions, or whether they only benefit individuals with bowel disorders. Peter plans to investigate the prevalence of Parkinson’s in other patients who take these drugs, such as those with psoriasis or rheumatoid arthritis.
Because not all Parkinson’s patients will have inflammatory bowel disorders, findings from the investigations into the co-occurrence of the two conditions might not generalize to everyone with the neurodegenerative disease, Mazmanian says. Still, these studies and many others that have emerged in recent years support the idea that the gut is involved in Parkinson’s is correct, he adds. “If this is indeed true, it allows us to now devise interventions that target the gut instead of the brain.”
Already, some researchers have started to test such interventions. In 2015, Zasloff and his colleagues launched a company, Enterin, that is currently testing a compound that slows alpha-synuclein aggregation in the gut. Although the treatment is intended to reduce non-motor symptoms of Parkinson’s, such as constipation, the researchers hope that by targeting early gut pathology, they will be able to restore—or prevent—the disease’s effects on the central nervous system.
https://getpocket.com/explore/item/does-parki...ket-newtab
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