What if a single drug could cure obesity? According to some research I've been following, we're not far off from that reality. There's no question that whoever controls the market for such a groundbreaking obesity drug holds the keys to mind-blowing wealth. Here's everything you need to know for a shot at the ground floor...

During the last several decades, there has been a dramatic increase in obesity in the developed world. With the rise in body mass indexes are negative effects on metabolism, including cholesterol, blood pressure and insulin resistance.

A recent CDC study estimates that more than $147 billion per year of health care expenses are attributable to obesity. The Department of Health and Human Services believes that obesity may account for 300,000 deaths a year in America. A plethora of pills, potions, creams and lotions of dubious effectiveness are peddled in order to satisfy this growing need to reduce body fat.

Usually, we treat weight loss as an act of willpower and discipline. There are, however, clear biological signaling pathways that influence appetite, metabolism and body weight beyond our direct conscious control.

For instance, in 2007, researchers demonstrated that when a population of mice were fed a high-fat diet, some grew obese, while others did not. Fatty tissue produces a hormone called leptin.

Leptin sends a signal to the brain that makes it control appetite and metabolism. The researchers thought that increasing leptin levels in the obese mice would cause weight loss. It didn't. They discovered that while both obese and normal mice had leptin circulating in their bloodstreams, the mice that gained weight had a deficiency in leptin receptors in the hypothalamus region of the brain. These mice did not respond to increased body fat in the same way as the others did.

More recently, Harvard Medical School collected blood samples from newborns and measured them for the leptin hormone. They discovered that the more leptin the babies were born with, the lower their body mass index was at the age of 3.

But that's not all. There may also be a viral vector that leads to an increased risk of obesity.

Closely related to the common cold, human adenovirus 36 (AD-36) was first identified in humans in 1978. More recently, this virus has been shown to be associated with obesity. For example, in 1988, a viral epidemic had swept through poultry flocks, killing thousands. Oddly enough, however, the dead poultry had a larger amount of body fat than healthy birds.

This got Dr. Nikhil Dhurandhar of Louisiana State University researching a possible connection. He showed that AD-36, when injected into chickens, caused a large increase in body fat. This effect has also been demonstrated in nonhuman primates.

Further investigation revealed that stem cells infected with a gene from AD-36, called E4 ORF-1, were much more likely to differentiate into fat cells than cells that did not express the gene. This, by the way, makes obesity a prime candidate for the anti-viral technologies of last month's Breakthrough Technology Alert pick. These therapies also have the potential to turn off the fat switch.

Dr. Dhurandhar has coined a neologism for this kind of obesity, infectobesity. According to him, seven viruses have to date been reported to cause obesity in animals. The possibility that the origin for much obesity is viral has enormous health and investment implications.

If this new theory of obesity seems unlikely to you, remember the resistance to the discovery that H. pylori bacterium caused stomach ulcers. The medical establishment ridiculed such an unconventional explanation for a condition widely attributed to the anxiety produced by modern living. Ultimately, however, these researchers who identified the bacterial cause were proven right and received the Nobel Prize for their efforts.

To quote Baruch Spinoza: Be not astonished at new ideas; for it is well-known to you that a thing does not therefore cease to be true because it is not accepted by many.

In the meantime, privately held Cambridge, Mass.-based Zafgen is designing a nanotechnology-enabled drug that directly homes in on human fat tissue. Most experimental drugs for obesity work by helping the brain improve its ability to interpret biological signals to regulate appetite and metabolism. Zafgen takes an entirely novel and revolutionary approach, based in part on research by MD Anderson Cancer Center researchers Wadih Arap, Renata Pasqualini and Mikhail Kolonin. Essentially, they treat adipose tissue similarly to tumors.

Understand that all cells have expiration dates. When the signal comes to die, they should do so. But in some cells, mutations arise that cause them to ignore these signals. So they continue to divide uncontrollably and cancers develop. These researchers had been developing technology to cure cancerous tumors by destroying their blood supplies, literally starving these cells to death.

That's when they had the game-changing idea. The same technologies could be applied to obesity.

Zafgen is testing new drugs that shrink fat tissue by attacking its blood supply and inducing apoptosis - cell death. In animal studies, subjects lost 25% of their body weight in weeks. The method not only removed external body fat, which makes up beer guts and love handles, but it also removed the dangerous fat that envelopes organs. Moreover, the drug took out only the bad white fat, leaving beneficial brown fat untouched. Obese mice used for the early tests remained healthy. They also ate less. Once their weight leveled off, they started to eat more food without putting on weight.

No one is really sure why this happens, but it is possible that fat tissue creates its own positive feedback loop to encourage more fat tissue to form. Possibly, it creates a source of stem cells that differentiate into new fat cells and grow into more fat tissue.

Zafgen plans on putting its new pharmaceutical into clinical trials soon. If successful, it will have developed a magic bullet cure for obesity. We are watching this space carefully and will keep you up-to-date. This could come to market before almost anyone expects.

For transformational profits,
Patrick Cox

December 9, 2009

Medicine