Can the Newly Discovered Obesity Genes Help You Lose Weight?

Can the Newly Discovered Obesity Genes Help You Lose Weight?

Overweight? You can now officially blame it on your parents. Or at least the genes they passed along to you.

Quite a few research papers published recently have shown that mutations in genes can control your appetite and your ability to burn calories. Genetic makeup affecting a person's weight isn't all that surprising, considering that people tend to have weight similar to their parents, but it's nice to have an increasing body of scientific data to support the observation.

In one study, researchers showed deletions in the Mrap2 gene caused mice to weigh twice as much as their siblings even though they ate the same amount, implying the gene is involved in burning the calories.

Another gene, FTO, has long been linked to obesity, but a recent study showed how mutations in the gene leads to higher weight by increasing the level of ghrelin, a hormone that signals to the brain that you're hungry.

In a third study, researchers sequenced the SIM1 gene, another gene associated with obesity, in 2,100 patients with severe, early-onset obesity and in 1,680 controls. They discovered 13 different variants in SIM1 in 28 unrelated obese patients, including several that weren't found in the control patients that reduce the protein's activity significantly.

A weighty issue
How's this going to help you lose weight? It can't. At least not yet.

Figuring out that you have one of these mutations is fairly easy. DNA sequencing is getting cheaper by the day. But it's not as if you can change your genes. Maybe someday, but I'd guess not in your lifetime.

More likely, though, understanding the biology of obesity can help researchers develop drugs to control appetite and burn calories by interacting with the proteins involved in the metabolism process, especially if doctors know which proteins in the patient are functional.

For instance, a drug that increases FTO activity should lead to decreased appetite. Similarly, increasing Mrap2 activity may increase calories burned.

Like we've done already
With our limited knowledge of appetite and metabolism, drugmakers have already developed some drugs to treat obesity.

Eisai and Arena Pharmaceuticals' Belviq activates the 5-HT2C receptor, which activates a polypeptide that makes you feel full. It's easier to lose weight if you don't feel like eating.

VIVUS' Qsymia is a combination of two drugs. Phentermine promotes reduced appetite through the release of catecholamines. The other component, topiramate that's released over time, was originally developed by Johnson & Johnson to treat epilepsy. It isn't clear exactly how the drug promotes weight loss, but there's probably something going on in the brain, as the drug is also used to prevent migraines.

Contrave, being developed by Orexigen , is also a combination drug containing naltrexone and bupropion, the latter of which was developed by GlaxoSmithKline as an antidepressant that is also used to help people stop smoking. Combined, the drugs stimulate pathways that increase energy expenditure and reduce appetite.

Orlistat, which is sold by Roche as Xenical and by GlaxoSmithKline as a lower-dose over-the-counter formulation called Alli, reduces caloric intake by blocking the absorption of fats so they pass though the body.

The new information on genes involved in obesity could potentially help those drugs already on the market, because the drugs seem to affect patients differently.

For instance, in two combined studies of Belviq, 22.4% of the patients lost at least 10% of their body weight, compared with just 8.7% in the placebo group. The drug clearly works really well on some patients but much less so in others -- the mean weight loss for the entire population was just 5.8%.

It seems possible that the responders have a different genetic makeup that causes them to respond to the drug. If researchers can find the gene -- perhaps one of the ones recently linked to obesity -- doctors might be more inclined to prescribe the drug, since they'll have confidence that the drug will help the patient.

Segmenting the population would reduce the potential market size, but it might increase the usage of the drug, because the increased weight loss would justify the potential side effects. Companies could also justify charging more for their obesity drug if it was clear the drug was going to produce a substantial weight loss, which is a precursor to other diseases.

Until that happens
It'll be years before drugmakers might find a genetic connection for their responders and prove it in a trial -- if they want to even bother -- and even longer to develop a new drug based on the new proteins involved with obesity.

Until then, investors' only option to take part in the obesity market is to buy shares in Arena, VIVUS, or Orexigen. Unfortunately, Arena's Belviq and VIVUS' Qsymia are far from achieving their blockbuster potential; the companies have struggled to get doctors to prescribe the drug and patients to pay for them. Contrave isn't even on the market yet, because the Food and Drug Administration made Orexigen run another study.

They may be blockbusters someday -- there's certainly potential given the 60 million obese Americans -- but it could take years for doctors to feel comfortable prescribing drugs to the masses. Persuading insurers to pay for them has been easier than in the past, but they're still a long way away from gaining coverage seen for a typical drug.

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