War on Fat Won?

Now drug companies are scrambling to get their hands on the patent and rush the drug to market.

And Maria Rupnick may go down in history as the woman who won the war on fat – a war that claims the lives of several million people each year due to obesity related diseases like diabetes and heart disease.

The drugs are called angiogenesis inhibitors and they work by killing off the blood vessels that feed tumors. Unlike radiation and chemotherapy, they do not have the negative side-effects of nausea or hair loss.

But this miracle medicine is proving even more effective at fighting fat than battling cancer.

“I didn’t go into this to find a cure for obesity,” explains Dr. Rupnick, “Fat just looked like the best way to study whether or not blood vessels control normal tissue just like they control tumors.”

Fat and cancer share a unique property – both need a lot of blood to keep growing. To get it, they form tubes called blood vessels that hook into veins and arteries.

“They sprout,” says Rupnick, “like new branches on a tree.”

This process of forming new blood vessels is called ‘angiogenesis’ and angiogenesis inhibitors interfere with it in a number of ways depending on the particular drug.

If you stop the tumors from growing new blood vessels by using angiogenesis inhibitors, then the cancer can no longer grow or spread.

Maria Rupnick wanted to know if the drugs would have the same effect on fat. “If there is angiogenesis in fat growth, then if you stop the angiogenesis you should stop the fat growth.”

To test her theory, Rupnick recruited hundreds of super fat mice. Each are the rodent equivalent of a Sumo Wrestler, weighing more than three times the weight of a normal mouse.

The mice belong to a particular strain called OBOB. “They are a normal mouse that lacks the hormone lepton,” explains Rupnick. “Lepton tells the brain, ‘I’m full.’

These animals don’t have that so they eat and eat. They end up being furry balls of fat with a tail.”

When Dr. Rupnick and her team began giving the fat mice the angiogenesis inhibitors, they expected the animals would stop gaining weight.

“We not only saw that,” recalls Rupnick, “but they lost a tremendous amount of weight! They were losing 1/60th of their body weight every day. They quickly went from their obese weight of more than 75 grams to the weight of their normal counterparts at 25 grams.”

What is that in human terms? “So if someone were 75 kilograms, he would lose 1.5 kilograms a day!” says the excited scientist.

“Depending on the angiogenesis inhibitor, they lost more or less. Taken off the drug, they would regain the weight. We did that over and over again.”

At first the researchers were worried that the drugs were poisoning the animals and that was why they were losing so much weight.

“But the animals were fine,” says Rupnick. “OBOB mice are usually sedentary, but these guys actually became active like their normal counter-parts.”

“So I spoke to experts in the obesity field and they didn’t buy it,” remembers Rupnick. “I received pretty harsh criticism. I was even told by one very prominent person that they had seen many young scientist’s careers crash and burn by doing things just like this.”

“A lot of whether or not you make it or break it in science depends on the decisions you make at a given crossroads and how far ahead you can see. And there is such a fine line between persistence and stubbornness.”

“It was a frightening decision to keep going, because I didn’t have an explanation for what was happening. And the paper got rejected so many times I lost count. And the grants got rejected.”

Despite the opposition and lack of funding, Maria Rupnick decided she couldn’t ignore the amazing results. The obesity epidemic was too serious to pass up an opportunity to help.

“I initially wanted to go into research because you could potentially help thousands of people, in a hospital you only help one at a time.” Dr. Rupnick felt this was her chance and redoubled her efforts to prove her work.

“We spent a lot of time trying to make sure the animals weren’t sick,” says Rupnick. “We had veterinarians check them and the animals were fine.”

“But a pharmacologist and toxicologist told me I could never 100% prove they weren’t being poisoned. I went home depressed and watched Law and Order on television. The attorneys were having a hard time proving their case. Then one said, ‘Well, if we can’t prove that this person committed the crime. Than we have to prove who really did it.’”

“It was an ‘AHAA moment’ for me. I had spent months trying to disprove toxicity. What I should have done instead was figure out what was causing the weight loss. If it is a normal, what is it?”

After months of searching, Dr. Maria Rupnick found the missing piece of the puzzle. It turns out that it was something that stares us in the face every time we put on a bathing suit and check to see if we look fat.

Fat is special.

Explains Rupnick, “if you eat ten pizzas, you’ll gain weight. Even if your weight has been stable forever. And if after ten years you suddenly don’t have access to food, your fat tissue is going to shrink.”

We’ve all experienced putting on a few pounds during the Holidays or struggling to lose ten pounds for that vacation to the beach, so we take it for granted. But, biologically speaking, this is very unique. Your heart doesn’t get bigger or smaller depending on what you eat.

“The blood vessels in fat tissue must specialize to accommodate that ability to grow and shrink,” says Rupnick. And that was the key.

Like many people, blood vessels become less adaptable as they get older. Your heart won’t grow or shrink because its blood vessels are too old and rigid.

But fat is the Peter Pan of the body, it never quite grows up. “The blood vessels that supply fat tissue never fully mature,” explains Rupnick. “That keeps them readily able to grow or shrink as you need.”

But this eternal youth has a price. “The payback is they are vulnerable to angiogenesis inhibitors.” That was the missing link, the reason the fat was melting away.

As its blood vessels die off, the fat cell is forced to get rid of bulky fat to survive –Like sailors on a sinking ship who start throwing everything overboard to stay afloat.

This discovery goes way beyond helping people lose fat, it will also help angiogenesis inhibitors beat cancer.

Chemotherapy and radiation kill cancer by destroying everything around it, including healthy tissue. It is like a nuclear bomb. The big advantage of angiogenesis inhibitors is they only attack the cancer, like a smart missile.

But, despite their promise, the results have been mixed. The US Food and Drug Administration has approved one angiogenesis inhibitor called Avastin, but many others have been held up by mixed results in clinical trials.

Dr. Rupnick’s findings are the missing link. Angiogenesis inhibitors can be made more effective by first using drugs that de-mature the blood vessels in the tumors making them more vulnerable.

The opposite can make fighting fat even easier. Maria Rupnick discovered that if she gave the mice drugs to age the blood vessels in their fat, then the mice became frozen at whatever weight they were. “They just stabilized out,” says Rupnick, “the animals couldn’t gain weight or lose weight.”

Now Rupnick and her team are developing a two step fat fighting system. First they melt away excess fat with angiogenesis inhibitors, then they lock the new weight in with drugs that mature the blood vessels within the fat.

Imagine safely losing 30 pounds in a week and then taking a pill along with your daily vitamins that will guarantee that you will never gain it back. It will be a revolution in how we deal with fat.

“The problem we had in treating obesity is that we didn’t understand it,” says Rupnick. “We blamed it on the patient.”

Doctors would never tell someone with diabetes, “just be more disciplined.” But that is exactly what many fat people are told. “Obesity is a deregulation of body weight just like diabetes is a deregulation of blood sugar,” says Rupnick. “It is a disease.”

And now being fat may have a cure.

When asked when we might see these drugs on the market, Dr. Rupnick said it was too early to say. “Obesity being the epidemic that it is, the FDA wants to push it towards clinical trials as fast as possible. But, I think it is too dangerous to even speculate.”

The fact that the drugs have already been approved for treating cancer will go a long way in speeding up the process. It is possible we might begin seeing ‘fat melting’ medicines available world-wide in the very near future.

But there are still questions to be answered. “There is a huge difference between a mouse and a man. Right now we can say that we can make mice look pretty good,” says Maria Rupnick. “We don’t have any indications yet that it won’t translate to humans, but the place where you always get into trouble in science and medicine is that you don’t know what you don’t know. Still, I would say it is hopeful.”

If the drugs end up fulfilling their promise we may be entering a Fat Free millennium. Since the 1930’s most industrialized countries have been fortifying milk and bread with nutrients. This century may eventually see the same being done with the ‘anti-fat drugs’ being developed by Maria Rupnick.

“The only way you can get a drug from the lab to the bedside is to have a drug company pay for it. There is no other way to fund, develop, or market these things.

Because of that reason, it may end up going in that direction and I can’t control that.”

But the idea disturbs her. “Obesity is a disease, and I want this to be a treatment for a disease,” says Rupnick, “not to lose 5 pounds for the little black dress on Saturday.”

“If your objective is to eat poorly, and not exercise, and just take the pill a couple of days before you want to go out; I couldn’t be more opposed to that. Because the drug itself may be safe, but what you’re really doing is abusing yourself. This is not supposed to allow you to eat ten thousand hamburgers.”

But despite Doctor Rupnick’s reservations, her drugs may end up being used in precisely that way.

- The End -
Lance Laytner
Meritum Media
Copyright 2008

click on photos for LIGHTBOX

THESE TWO MICE WERE ONCE ALMOST IDENTICAL. AFTER JUST

DOCTOR MARIA RUPNICK MAY GO DOWN IN HISTORY AS THE

THIS FAT MOUSE MAY SAVE YOUR LIFE. OBESITY CAUSES A NUMBER OF HEALTH PROBLEMS INCLUDING HEART DISEASE AND DIABETES. THE RESEARCH BEING DONE ON THIS MOUSE MAY SPELL THE END OF OBESITY AND A NEW ERA OF IMPROVED HEALTH. PHOTO BY LANCE LAYTNER MERITUM MEDIA

OUR BODIES WERE SIMPLY NOT BUILT FOR THE KIND OF OVEREATING THAT IS POSSIBLE IN OUR MODERN WORLD. THE RESULT IS 'GLOBESITY,' A WORLD-WIDE EPIDEMIC OF FAT RELATED DISEASES. PHOTO BY RON LAYTNER EDIT INTERNATIONAL

IF ANGIOGENESIS INHIBITORS PROVE AS SUCCESSFUL ON HUMANS AS THEY HAVE ON THESE MICE, THE CHOICE BETWEEN FAT AND THIN MAY BE AS EASY AS TAKING A PILL WITH YOUR VITAMINS. PHOTO BY LANCE LAYTNER MERITUM MEDIA

HUNDREDS OF MICE HAVE BEEN TESTED BY DR. RUPNICK AND OTHER LABS AND THE RESULTS ARE IRREFUTIBLE - ANGIOGENESIS INHIBITORS WORK BETTER THAN COULD HAVE BEEN IMAGINED. PHOTO BY LANCE LAYTNER MERITUM MEDIA

WHEN RUPNICK FIRST STARTED WEIGHING THE MICE AFTER GIVING THEM THE DRUGS, SHE WAS SHOCKED. THE MICE WERE LOSING MORE THAN 1/60th OF THEIR BODY WEIGHT EACH DAY. PHOTO BY LANCE LAYTNER MERITUM MEDIA

EVERY PHASE OF HER WORK IS CAREFULLY DOCUMENTED BY MARIA RUPNICK, A TOP AMERICAN SCIENTIST WHO EARNED A MEDICAL DOCTORATE FROM HARVARD AND A PHD FROM THOMAS JEFFERSON UNIVERSITY IN PHYSIOLOGY, CELL BIOLOGY, AND MATHEMATICAL MODELING. PHOTO BY LANCE LAYTNER MERITUM MEDIA

HERE A CLUSTER OF FAT CELLS IS SHOWN WITH THE HELP OF A HIGH POWERED ELECTRON MICROSCOPE. THE TENDRILS THAT LOOK LIKE YELLOW VINES ARE BLOOD VESSELS. ANGIOGENESIS INHIBITORS KILL THEM CAUSING THE FAT CELLS TO SHRINK AND EVENTUALLY DIE. PHOTO BY SCIENCE PHOTO LIBRARY

LIKE A PROUD PARENT, MARIA RUPNICK SHOWS OFF THE MICE THAT MAY CHANGE THE FUTURE OF WEIGHT LOSS. PHOTO BY LANCE LAYTNER MERITUM MEDIA