GLP-1 Levels Linked to Brain Inflammation in Autoimmune Disorder, Study Shows

Elevated levels of the gut hormone glucagon-like peptide-1 (GLP-1) may increase brain inflammation in patients with neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune disorder that causes inflammation in the spinal cord and eye nerves, according to research presented today at the 150^th Annual Meeting of the American Neurological Association.

GLP-1 is a natural gut hormone that is produced after eating. It can lower blood sugar, slow digestion and control appetite. GLP-1 drugs mimic this hormone to help patients lose weight and control their diabetes.

However, this study suggests GLP-1 and its receptor, GLP-1R, may cause area postrema syndrome (APS), characterized by severe nausea and vomiting, a main symptom for some NMOSD patients—up to 10% of NMOSD patients list APS as their first symptom, while up to 30% develop it.

“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, Ph.D., a physician at the First Affiliated Hospital of Zhengzhou University, China, said in a news release.

To come to this conclusion, Yang and his team measured the GLP-1 and GLP-1R levels in the spinal fluid and blood of 248 NMOSD patients, 57 of whom had APS. Findings were compared to 164 patients without NMOSD or APS.

The team found much higher levels of GLP-1 and GLP-1R in patients with APS than patients with just NMOSD or with NMOSD.

Researchers also studied mice with APS-like symptoms, determined by brain cell overactivity observed in the area postrema. When the mice were given Exendin-(9-39), a drug that blocks GLP-1R, brain overactivity decreased.

“…Our findings don’t mean that GLP-1 drugs are automatically harmful or cause inflammation on their own,” Yang continued. “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.”

Worldwide, NMOSD affects between 1 in 10 per 100,000 individuals. Women are nine times more likely to have it than men. Asian and African American populations are two to three times more likely to have it than White patients.

The pain, loss of vision and paralysis associated with NMOSD are caused by the immune system attacking the optic nerves, spinal cord and sometimes parts of the brain.

NMOSD can be difficult to diagnose, and 40% of patients report being initially misdiagnosed with multiple sclerosis due to some overlapping symptoms, such as nausea, optic neuritis and motor disability. NMOSD can be diagnosed using a blood test that looks for anti-aquaporin-4 (AQP4-IgG) antibodies, which are present in up to 80% of cases.

There is currently no cure for NMOSD, but symptoms can be managed using steroids, immunosuppressants or biologic drugs.

Yang presented his research this morning during a presentation titled, ‘GLP-1/GLP-1R-mediated Glycolytic Reprogramming Drives Area Postrema Neuronal Hyperactivity in Neuromyelitis Optica Spectrum Disorder.’ It was part of a session titled, ‘Glucagon-like Peptide-1 (GLP-1) Receptor Agonists—The Ultimate (Antiaging) Gateway Drug?’

The 150^th Annual Meeting of the American Neurological Association is being held from September 13 to 16 in Baltimore, Maryland.