The Tastemakers: Semonyx Targets Taste Receptors

Abstract

Ewing, New Jersey, based Redpoint Bio (http://www.redpointbio.com) focuses on taste biology to develop drugs for diabetes that control metabolism as well as natural taste enhancers to reduce the calorie content of sweetened foods. The now 12 person company (restructured this spring) originally focused on using molecular cloning and screening techniques based on work done in the lab of company founder Robert Margolskee, M.D., Ph.D., now at Monell Chemical Senses Center. The public company currently has $7.5 million in cash.As industry focus has shifted to finding natural ingredients, Redpoint has developed some new variations on classical pharmacology to find new compounds. “We've gone back to behavioral models of taste,” said Raymond Salemme, Ph.D., Redpoint Bio CEO. But natural products are often impure and can produce off-target effects in cell-based assays that are often difficult to sort out. To complement its cell-based assays, Redpoint employs trained rodents. “It is classical Skinner box stuff,” said Salemme. “You can train an animal to make a discrimination. If they make the right discrimination, they press a lever and they get a food pellet. We have computerized everything and put a sample plate under the bottom of the animal's cage, providing fairly high sample throughput. The animal sticks his tongue in a well and interrupts a laser beam. We can see how many times the animal actually licks the sample to see how much he likes it. ”According to Salemme, researchers have observed that the symptoms of diabetes frequently cease in morbidly obese people who undergo radical bariatric surgery. This is consistent with the proposed role of taste or related chemosensory signaling circuits in the gut that can provide feedback signals that control hunger and metabolism. Redpoint Bio is working on developing compounds that work on gut signaling as novel therapies for diabetes.Redpoint Bio uses cheminformatic approaches for navigating chemical space to find new natural products with desirable taste properties. “One thing that people are interested in is finding natural high-potency sweeteners that come from a fermentation source that could be cheaper to produce than farming plants like stevia,” said Salemme. However, Redpoint Bio has no current funded collaborations. “It has been a rough environment for biotech,” says Salemme.Some consumer advocates question the regulation of these new flavor ingredients. As they appear in minute quantities, they are not identified on product labeling. Potentially more controversial is the question if the tongue and brain registers something as sweet that really isn't, does the metabolism concur?“To play with the taste perception may not be harmful” said Bedrich Mosinger, M.D., Ph.D., senior research associate, Monell Chemical Senses Center. “However, we find taste receptors on endocrine cells in the body. We currently study in detail their physiological role, but we already know that they participate in regulation of release of several hormones. Therefore, agents that affect taste may also affect hormonal balance.” Who could imagine that feeding our sweet tooth could be so complicated?“We are responding to our clients' desires and they are responding to consumers desires.” said Jeannine Delwiche, Ph.D. senior scientist at flavor giant Firmenich. “The dream compound would be something that would be sweet, cheap, natural, and low calorie without side effects, and we'd like it to have the same functional properties as sucrose.”