Harnessing olfactory receptors to make fragrances or flavors universally appetitive

Prof. Bob Datta and his team at Harvard Medical School have discovered a new class of odorant receptors that is structurally distinct from previously known receptors. These receptors respond to a variety of innately-relevant cues, including pheromones and fatty acids, and defines a new neural logic through which olfactory sensory information is translated into perception. The team developed a series of in vitro and in vivo assays to identify small-molecule ligands capable of activating specific members of this receptor class.

The Harvard team has discovered that MS4A receptors are expressed on guanylyl cyclase (GC-D) positive olfactory sensory neurons, accessory cells part of the “necklace” subsystem that resides in the recesses of the olfactory epithelium. Like the MS4A ligands, may of the molecules previously shown to trigger activity within the necklace olfactory system also have innate meaning for mice. In fact, data from the literature suggests that stimulating the cells on which the MS4A receptors reside, can significantly increase food intake in mice by hijacking innate preference mechanisms.

Compounds activating the MS4A receptors could be used as food or fragrance additives that make moderately appetitive stimuli more appetitive. These safe additives, based on completely novel biology, could provide more salient and attention-grabbing cues, stimulating learning and attentional processes that make food more palatable. The science of the MS4As represents the first truly new opportunity to develop a new class of compounds with the potential to influence human and animal olfactory perception.

Intellectual Property Status: Patent(s) Pending