GLP-1 hormone may trigger brain inflammation in NMOSD patients
Study urges caution for therapies, like Ozempic, that target the GLP-1 pathway
The gut hormone GLP-1 may contribute to brain inflammation in people with neuromyelitis optica spectrum disorder (NMOSD), leading to episodes of uncontrollable nausea, vomiting, or hiccups — a condition known as area postrema syndrome (APS), a new study suggests.
These findings raise a crucial question about the use of GLP-1-like therapies, such as the popular weight-loss and diabetes drug semaglutide (sold as Ozempic, among others), in NMOSD patients.
“We found that this hormone, which is usually helpful in other conditions, can actually make things worse for people with APS by overstimulating certain brain cells,” Lingfei Yang, PhD, a physician at the First Affiliated Hospital of Zhengzhou University, in China, and one of the study’s researchers, said in a press release.
The perplexing GLP-1 link
“However, our findings don’t mean that GLP-1 drugs are automatically harmful or cause inflammation on their own,” Yang added. “Instead, they may trigger stronger reactions in people who already have inflammation in the brain, like those with NMOSD. We need more research to understand whether these drugs should be used with caution in these patients — or if they could even be adapted to help with more targeted treatment.”
Yang presented the data recently at the 150th Annual Meeting of the American Neurological Association, held Sept. 13-16, in Baltimore, Maryland. The abstract was titled “The Pathological Mechanism of GLP1/GLP1R-Mediated Glycolytic Reprogramming in Area Postrema Neurons involved in APS-attacked NMOSD.”
In NMOSD, the immune system attacks the spinal cord and the optic nerves, which relay signals from the eyes to the brain. This can cause symptoms that include loss of vision, weakness in the arms and legs, paralysis, and pain.
APS is the first symptom in up to 10% of people diagnosed with NMOSD, with up to 30% developing APS symptoms at some point over the course of their illness. However, the underlying metabolic mechanisms of APS remain poorly understood.
GLP-1 is a naturally occurring hormone released into the gut after eating, which lowers blood sugar and slows down digestion, thereby controlling appetite.
In the study, researchers in China investigated the role of GLP-1 and its receptor, GLP-1R, in NMOSD-associated APS.
The team first measured the levels of GLP-1 and GLP-1R from the blood and spinal fluid of 248 NMOSD patients, including 57 with APS, as well as 164 individuals without NMOSD or APS.
What the data show
Data showed that NMOSD patients with APS had significantly higher levels of GLP-1 and GLP-1R compared with other NMOSD patients without APS and with those without the disease.
The researchers also found a significant correlation between higher levels of GLP-1 and GLP-1R in spinal fluid and greater NMOSD severity, as assessed by the Expanded Disability Status Scale, and APS symptoms, as indicated by scores on the revised NMOSD Pregnancy-Unique Quantification of Emesis.
Using a mouse model with APS-like symptoms, the team found that brain cells in the area postrema, the region responsible for APS, were overactive and showed signs of abnormal energy use, leading to nausea and vomiting. When mice were treated with a drug that blocks GLP-1R, the production of GLP-1 and GLP-1R decreased in the area postrema, lessening brain cell overactivity and easing APS symptoms.
The team also found that Enspryng (satralizumab-mwge), an injection therapy approved for adults with NMOSD, may help reduce GLP-1 levels in gut tissue.
“Targeting GLP1R signaling may offer a novel therapeutic strategy to mitigate APS symptoms and improve outcomes in NMOSD patients,” the researchers wrote. “This study highlights the importance of metabolic regulation in autoimmune neurological disorders and provides new insights into the [development] of NMOSD.”
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