Targeting inflammation could treat metabolic syndrome's many symptoms

There is no silver bullet to treat metabolic syndrome, a collection of maladies that raise a person’s risk for heart disease and diabetes. But Feinstein Institute-led researchers have come a step closer by using an Alzheimer’s drug to reduce inflammation in people with the syndrome.

Physicians typically treat metabolic syndrome by prescribing lifestyle changes or medicines such as blood pressure drugs and statins to lower cholesterol. The Feinstein team instead zeroed in on inflammation, which plays a key role in metabolic syndrome. They picked galantamine, an FDA-approved Alzheimer’s drug, because it is known to decrease inflammation in obese mice.

"It's been very tough to come up with a treatment that targets all the components of metabolic syndrome, which is becoming a pandemic because it stems from obesity," said corresponding author Valentin Pavlov, an associate professor at the Feinstein Institute, in a press release. "By repurposing galantamine, it means we don't have to start from zero to establish its safety. We already know it's safe."

In a 12-week trial, the researchers gave escalating daily doses of galantamine to a group of 30 patients, while another group of 30 received a placebo. They measured the levels of inflammatory molecules in the patients’ blood, as well as other markers, including insulin levels, insulin resistance and heart rate.

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They found that the group treated with galantamine had “significantly reduced” levels of inflammatory molecules and higher amounts of anti-inflammatory molecules compared to the placebo group. Additionally, the treated group had comparably lower insulin levels and insulin resistance. The findings are published in JCI Insight.

Galantamine treats Alzheimer’s by blocking an enzyme that breaks down the neurotransmitter acetylcholine, conserving more of the chemical for communication between neurons.

“What galantamine does [in metabolic syndrome] is activate the nervous system to decrease inflammation," said co-author Yael Tobi Harris, M.D., of North Shore University Hospital and Long Island Jewish Medical Center. "And because the inflammation is causing insulin resistance … we then see a decrease in insulin resistance."

The data suggest targeting inflammation could be a way to address the multiple faces of metabolic syndrome: "Bringing down inflammation and insulin resistance may reduce the risk of cardiovascular disease and other complications,” said co-author Kevin Tracey, M.D., CEO of the Feinstein Institute.

But getting the drug approved for metabolic syndrome will require more investigation. The researchers are calling for longer trials with more patients, as well as studies looking into galantamine's effect on diabetes.