Obesity treatments aren’t working – what’s next? Part 2 of 3

As we noted in our recent post (Innovation on the way to treat obesity?), the medical community and the country as a whole has struggled to curb the seemingly rampant rise of obesity.  In short, treatment options have failed; surgical approaches often come up short as patients rebound to their original weight within a handful of years; and medications can put undue stress on the cardiovascular system, which limits weight loss efficacy.

Medication to this point has been crudely focused on appetite suppression instead of directly reducing actual adipose tissue. Many obesity medications interact with the pleasure centers of the brain to provide a feeling of satiety; in fact, they have been used as anti-depressants.

Going one step further, Yale University researchers have shown that high fat foods activate the pleasure center, creating the potential for addiction. “’The idea is that if the brain adapts to a drug or calories in such a way that your reward response is deficient, then these individuals would need to consume more of the same,’ said Ivan de Araujo, a professor of psychiatry at Yale University School of Medicine, in the Boston Globe. ‘When the reward system is weak, you do more to obtain the same reward.’” His research, published in Science, showed that by injecting a molecule called oleoylethanolamine into mice, mice found a low-fat meal satisfying. Could this be the next weight loss drug?

Weight loss with these types of medications have historically come at a cost: cardiovascular disorder (remember Fen-Phen?). In order to keep cardiac risk in check, these psycho-stimulants (for example, serotonin, noradrenalin, dopamine re-uptake inhibitor) must be approved for low dosage, limiting their effectiveness to 5 to 10 percent weight reduction.

Even with this track record and knowledge base, much of the industry has proceeded down the path of appetite suppression through the central nervous system.  Belviq and Osymia are recent entrants to the appetite suppression market (both of which had to be resubmitted to FDA due to safety concerns); once again, the focus lies on manipulating the pleasure centers to achieve a physical outcome.

For patients to experience better, longer term results, treatments need to surpass the current ceiling for weight loss – again, about 10 percent before serious side effects occur – by moving away from the central nervous system.  The only reliable way to achieve higher weight loss is to minimally activate the CNS and go straight to the fat itself. 

There are multiple ways of achieving that objective.  We’ve seen significant interest from the VC community in novel mechanisms of action that focus on local fat metabolism.  New therapies are in discovery that kick-start weight loss to bring about double digit reduction in one year.  After that year, patients then move to a more conventional weight loss regime of diet and exercise that can be sustained without altering brain activity.

Our next post will dig into specific treatments that we believe will have a profound impact on obesity – and may be only a few years away from the marketplace.

Image courtesy of UMHealthSystem, Flickr.