Approved Alzheimer’s Drug Could Reduce Inflammation in Patients with Metabolic Syndrome

A recent report published in the journal JCI Insight suggests that an existing Alzheimer’s drug could also be used to treat patients with metabolic syndrome, a condition characterized by high blood pressure, elevated glucose levels, high cholesterol and excess fat around the midline. An estimated 30 percent of adults in the US are affected by metabolic syndrome, which increases their risk of developing type 2 diabetes and cardiovascular disease.

As there is no treatment that addresses all of the symptoms of metabolic syndrome, doctors often prescribe individual drugs – such as statins to lower cholesterol, and metformin to control blood sugar levels – in an attempt to treat the condition. Inflammation is at the heart of metabolic syndrome, leading researchers at The Feinstein Institute to hypothesize that galantamine, an anti-inflammatory drug currently approved to treat Alzheimer’s disease, could also treat patients with metabolic syndrome.

“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 Dr. Valentin A. Pavlov, an associate professor at the Center for Biomedical Science, and Center for Bioelectronic Medicine at The Feinstein Institute for Medical Research. “By repurposing galantamine, it means we don’t have to start from zero to establish its safety. We already know it’s safe.”

Pavlov and his colleagues had previously tested the effects of galantamine in obese mice, and found that the drug had a lowering dampening on the inflammatory response. Armed with the results of their preclinical study, the researchers conducted a placebo-controlled clinical trial of galantamine in 60 patients with metabolic syndrome.

Patients were given an escalating dose of galantamine, or placebo, over a 12-week study period. Inflammatory biomarkers were measured over the treatment period, along with various metabolic and cardiovascular markers.

The researchers found that galantamine treatment was associated with an over 25 percent reduction in inflammation in patients with metabolic syndrome. This reduction in inflammation was also associated with decreased insulin resistance, compared with the placebo group.

“Galantamine can target the entire syndrome as well as targeting components of the syndrome,” said study co-author Dr. Yael Tobi Harris, chief of endocrinology, diabetes and metabolism at North Shore University Hospital and Long Island Jewish Medical Center, part of Northwell Health. “Using an existing drug is a much faster way of getting a treatment out there. It’s promising, it makes me optimistic, and it’s a starting point indicating an avenue of research that should be pursued further.”

Galantamine is an acetylcholinesterase inhibitor which prevents the neurotransmitter acetylcholine, from being degraded too quickly. As cholinergic function is impaired in patients with Alzheimer’s disease, the drug may help to compensate for this deficit and support normal cognitive functioning.

“What galantamine does is activate the nervous system to decrease inflammation,” said Harris. “And because the inflammation is causing insulin resistance . . . we then see a decrease in insulin resistance.”

Pavlov also noted that the doses used in this study were far below those prescribed to Alzheimer’s patients, suggesting that even low doses of galantamine could have an effect on metabolic syndrome-associated inflammation. As this early-stage trial involved a relatively small number of patients, the researchers stress that more research will need to be done to assess the efficacy of galantamine as a potential treatment for metabolic disease.

“These findings illustrate that it may be possible to treat inflammation in metabolic syndrome,” said study co-author Dr. Kevin J. Tracey, president and CEO of the Feinstein Institute. “Bringing down inflammation and insulin resistance may reduce the risk of cardiovascular disease and other complications.”