A chemical which is currently being investigated for the control of inflammation — important in multiple sclerosis, psoriatic arthritis and lupus — has also shown to have strong activity in increasing metabolism. The compound, ShK-186, is a synthetic form of a toxin first found in sea anemones which has been going through much testing for its medicinal properties. The chemical is licensed to a Seattle based biotechnology company, Kineta Inc., dating back to 2009, and just showed positive results in Phase I clinical trials which assessed its safety in healthy patients.

The current research, out of the University of California, Irvine, was published in the journal the Proceedings of the National Academy of Sciences. In the study scientists found that ShK-186 blocks a protein important in the induction of inflammation, the Kv1.3 potassium channel. Potassium channels can either allow or block the entrance of potassium ions in and out of cells. Previous studies using mice that were generically modified to lack the gene for Kv1.3 showed that mice without the potassium channel were less susceptible to obesity and had a higher baseline metabolic rate.

In the present study the researchers found that the chemical was helpful in mice that were fed a high-fat and high-sugar diet, which usually leads to obesity and diabetes in mice. They found that ShK-186 reduced weight gain, white fat deposits, fatty liver, blood cholesterol and blood sugar by activating calorie-burning brown fat, suppressing inflammation of white fat and augmenting liver function. Interestingly, the effects of the drug were not seen in mice that consumed a normal diet, suggesting that obesity causing diets may be acting uniquely on the potassium channel target.

"This is a new twist in a sustained journey of discovery made over the 30 years that charts the course for expeditious translation to humans who suffer from potentially lethal consequences of metabolic syndrome and autoimmune diseases," said Dr. George Chandy, professor of physiology and biophysics at UC Irvine and a Kineta scientific advisor. "We evaluated ShK-186 in an obesity model because it has high selectivity for the Kv1.3 target, a favorable pharmacokinetic profile, and meets the qualities of an industry-standard drug."

The drug is highly specific for the Kv1.3 potassium channel, which makes it ideal for use as a pharmaceutical drug. "These data are quite exciting and strongly support the notion that inhibition of the Kv1.3 channel provides a highly effective method for managing obesity and its associated metabolic abnormalities. The results obtained with ShK-186 are consistent with what one would expect to see with a potent inhibitor of this channel. While additional studies are needed, the potential clinical relevance of this work is enormous, since a significant number of people are afflicted with obesity and its associated complications, and no Kv1.3 inhibitor, as a drug candidate for obesity, has reached the clinic until now," said Dr. Gary V. Desir, professor of medicine at Yale University, and an expert on the Kv1.3 channel's role in renal potassium secretion and glucose metabolism. Dr. Desir was not a part of the present with the study.

Obesity is a major public health issue throughout the world, leading to diabetes, heart disease and loss of economic productivity. The World Health Organization estimates that worldwide obesity has doubled since 1980. They estimate that nearly 11 percent of the planet is currently obese, leading to an estimated 300 million diabetics by 2030 costing the global economy $260 billion annually.