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' (NASDAQ: ARNA  ) 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' (NASDAQ: VVUS  ) 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 (NASDAQ: OREX  ) , is also a combination drug containing naltrexone and bupropion, the latter of which was developed by GlaxoSmithKline (NYSE: GSK  ) 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.

Responders
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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Comments from our Foolish Readers

Help us keep this a respectfully Foolish area! This is a place for our readers to discuss, debate, and learn more about the Foolish investing topic you read about above. Help us keep it clean and safe. If you believe a comment is abusive or otherwise violates our Fool's Rules, please report it via the Report this Comment Report this Comment icon found on every comment.

  • Report this Comment On August 11, 2013, at 11:01 AM, amikarney wrote:

    the facts speak for themselves.

    in 8 weeks i already lost

    10% of my weight without any side effects.

    thanks Belviq!

  • Report this Comment On August 11, 2013, at 11:43 AM, JustPassinThru wrote:

    Article statement: "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."

    In the August 1 Arena conference call it was reported that real-world weight loss results are 200% to 300% what was seen in clinical trials. Other authors have commented that weight loss clinical trials are notoriously difficult to conduct for various reasons. Now that real-world weight loss is seen to be vastly improved from clinical trials, what's next? Maybe the % of responders in the general population? I wouldn't want to be caught betting against it! (like 60 millions short shares...)

    "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."

    The earlier two paragraphs were discussing Belviq, so it would seem that this is the drug your referring to that has the "potential side effects"?

    Of course a BIG marketing advantage of Belviq is that it is SAFE, with a slight headache that only lasts a day or two being the only reported side effect. Belviq was EXTENSIVELY tested due to FDA concerns about potential heart valve problems, so the "potential" for Belviq side effects was also indirectly tested through the observation of all of those test subjects in clinical trials. BOTTOM LINE: "potential" side effects are a NON-ISSUE with Belviq. Of course the same cannot be said of their nearest competitor, Qsymia (VVUS) that received a restrictive REMS with their FDA approval for a variety of reasons including cleft pallet fetal birth defects. (Now that IS a scary side effect!)

    Edgar Online Financials posted a link yesterday to Arena's second quarter income statement. The income statement shows that Arena went from three consecutive net income loss quarters (not unusual for pharmaceutical research companies befor a breakout) to the latest quarter with a +$40,100,000 net income. THIS IS BEFORE DIRECT TO CONSUMER MARKETING HAS BEGUN! Belviq's distributor is currently in the doctor education phase of the new drug distribution (which precedes DTC advertising). Weekly prescription counts are increasing steadily and at a higher rate then their most recent competition's rate (VVUS) during the same period of their drug startup. And Insider Monkey reported an 18% increase in institutional ownership of Arena stock in the last quarter.

    Not a good time to be short Arena. A GREAT time to go long!

    Cheers!

  • Report this Comment On August 11, 2013, at 4:59 PM, JessicaHopkins wrote:

    A few months ago I decided to finally loss a couple of pounds. I was wondering what kind of program to try out. Then one of my friends told me about .I had my doubts but I tried it and was really surprised at how well it worked. You can check out the site here http://tinyurl.com/kobgd5f.

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