A study entitled “Niclosamide ethanol amine–induced mild mitochondrial uncoupling improves diabetic symptoms in mice,” now published in October issue of Nature Medicine, reports modifications introduced to the current drug niclosamide may be used as a new treatment for Type 2 Diabetes.
Type 2 diabetes is the most common form of diabetes and is characterized by a deficient production of insulin (a peptide hormone produced by the pancreas), leading to higher than normal glucose levels in the blood, a condition known as hyperglycemia. The majority of current treatments ameliorate the hyperglycemic symptom, but no treatment available targets its underlying cause. One of the causes is the abnormal accumulation of lipids in the liver and muscle. Its accumulation prevents these organs to properly absorb glucose, thus, glucose accumulates in the blood leading to diabetes associated health conditions as blindness and cardiovascular diseases.
Mitochondria are key regulators of glucose and fatty acid metabolism. Mitochondria proteins called uncouplers when expressed in the liver or muscle of transgenic mice were shown to reduce intracellular lipid accumulation and even protect against insulin resistance (that would lead to hyperglycemia).
In this study, a team of researchers at Rutgers-RobertWoodJohnson Medical School modified a drug that was already approved by the FDA to treat intestinal infections of tapeworms.
Shengkan Jin, study leading author, noted, “Our goal in this study was to find a safe and practical way of diminishing fat content in the liver. We used mice to perform proof-of-principle experiments in our laboratory. We succeeded in removing fat, and that in turn improved the animals’ ability to use insulin correctly and reduce blood sugar.”
The drug in question – Niclosamide – mode of action is to uncouple the mitochondria of the parasitic worms, and it has a high safety profile. The authors show that niclosamide ethanolamine salt (NEN) can promote mammalian mitochondria uncoupling. In vivo, studies with mice showed that NEN administered orally increased their energy expenditure and lipid metabolism. Moreover, it prevented and treated hepatic steatosis (accumulation of fat in the liver), and insulin resistance in mice fed with a high-fat diet.
The team used a mice model for diabetes, db/db mice, and observed improved glycemic control in the NEN-treated db/db mice. Thus, in light of the obtained results, the authors suggest NEN as a new pharmacological approach for treating Type 2 Diabetes. Shengkan Jin is a cofounder of Mito BioPharm that has the exclusive right to use a patent owned by Rutgers to develop the commercial use of NEN.
