Rutgers researchers develop medicine tackling type 2 diabetes
A medicine developed by the Robert Wood Johnson Medical School might soon help treat the more than 25 million people who suffer from Type 2 diabetes today.
Niclosamide ethanolamine salt has shown success in preclinical testing, said Shengkan Jin, an associate professor in the Department of Pharmacology.
Type 2 diabetes is a chronic disease characterizing higher-than-normal glucose level in the bloodstream, Jin said. Obesity and aging contribute to the formation of the disease, but a person’s genetic component also plays a role.
Excessive fats in liver, muscle and adipose cells cause diabetes, he said. Normally insulin in the body stimulates cells into absorbing glucose, but too many lipids prevent the cells from responding to insulin correctly.
“When cells become insulin resistant, glucose that cannot be absorbed builds up in the bloodstream, leading to higher concentration,” he said.
Over the past few decades, type 2 diabetes has risen to a global epidemic level, partially due to the number of new patients every year, Jin said. The potential dangers with this form of diabetes include kidney failure, blindness and cardiovascular disease.
Keeping blood sugar in control includes reducing glucose intake through diet and taking medications that increase insulin release or liver’s sensitivity to insulin, he said.
“[These methods] require constant commitment and medication for life,” Jin said. “Patients who take them chronically are likely to develop drug resistance, which means these drugs are no longer as effective.”
Rather than controlling the disease, Jin’s research team focused on its cause.
The new medicine seeks to cure type 2 diabetes through a process called mitochondrial uncoupling, Jin said. Mitochondria are “cellular power plants” in the cell, converting glucose and fatty acids to adenosine triphosphate, molecular units of energy that move within cells.
Uncoupling is a process where fat gets burned off and spread as heat through the body, Jin said. When the amounts of lipids in the cells drop back to normal levels, the cells can work correctly again, absorbing glucose and preventing high blood sugar.
Liver cells are expected to reduce glucose levels the most, said Hanlin Tao, a post-doctorate researcher at the RWJMS.
“From experiments on mice, we saw that NEN can not only substantially prevent the formation of type 2 diabetes in mice that are fed with high-fat diet, but also stem the deterioration of the disease, or even reverse and cure it.” Jin said.
One of the biggest advantages of NEN is that it is a modified version of niclosamide, a Food and Drug Administration-approved drug, Jin said.
Niclosamide is presently used to treat intestinal parasites by uncoupling the mitochondria of parasite worms. It enjoys an excellent safety profile, Jin said.
NEN, a salt form of niclosamide, has higher water solubility and is easier for the body to absorb, he said. Experiments on mice and rats have shown an even better safety profile than niclosamides.
“A very little increase in body temperature can be seen in the use of our drug, but in a mild and controlled way,” Tao said. “It is because the burned fat is dissipated as heat but not continuously and excessively, since the half life of NEN is much shorter.”
Similar fluctuations in body temperature are natural to the human body and can be easily adjusted, he said. Working out raises the body temperature and sweating is a mechanism to reduce it.
NEN works differently than current medicines and so will avoid cellular drug resistance, Jin said. Since it treats the cause of the disease, it should be more effective while not requiring constant medication.
Encouraging evidence on safety issues brings NEN closer to commercialization, he said. The next step is having the FDA approve the compound after it reviews the medicine’s safety.
Yong Zhang, a licensing associate in the Office of Technology Transfer at the University of Idaho, contributed to the research and the patenting process when working at the RWJMS.
“One way to commercialize a drug is to [license] the intellectual property to a company with the exclusive use of developing, marketing and selling the patent technology,” Zhang said.
To facilitate the team’s effort in moving the project forward, Zhang became a patent agent registered to practice before the United States Patent and Trademark Office.
Mito BioPharm, a company cofounded by Jin in 2012, has an exclusive right to NEN’s patent, Zhang said. The University owns the patent.