No Trace of HIV After Stem-Cell Transplants, Researchers Say

Two more patients undergo 'sterilizing cure,' advancing understanding of the process

By Dennis Thompson

HealthDay Reporter

WEDNESDAY, July 2 (HealthDay News) -- Two HIV-positive patients show no trace of virus after receiving chemotherapy and stem-cell transplants as treatment for lymphoma, according to new research.

These patients have become the second and third known cases of a "sterilizing cure," in which medical treatment removes all traces of HIV -- the virus that causes AIDS -- from the body. They have remained virus-free even though doctors months ago took them off their HIV-targeted medications.

"We have been unable to detect virus in either the blood cells or the plasma of these patients," said lead researcher Dr. Timothy Henrich, of Harvard Medical School and Brigham and Women's Hospital in Boston. "We also biopsied gut tissue from one of our patients, and we were unable to detect HIV in the cells of the gut. Essentially, we do not have any evidence of viral rebound."

The findings are scheduled for presentation Wednesday at the International AIDS Society Conference in Kuala Lumpur, Malaysia.

The patients had been receiving long-term antiretroviral therapy for HIV when they developed lymphoma, a type of blood cancer involving white blood cells, Henrich said.

Both underwent chemotherapy followed by bone marrow transplants to cure their lymphoma. Afterward, Henrich could not detect any HIV infection in their bodies.

Henrich presented preliminary findings on the research at the International AIDS Conference last July. Since then, he and his research team withdrew the patients' antiretroviral therapy to see how completely the cancer treatment had rid them of HIV. One patient has been off treatment with no detectable virus for about 15 weeks, and the second patient for seven weeks.

Henrich warned that it is too soon to declare the patients completely cured of HIV. "Although we cannot detect HIV, it's possible it's there but in extremely low amounts," he said. "We're going to watch and wait, and see where it goes with these patients."

Unfortunately, this type of cure is not something that can be put into widespread practice for all people infected with HIV. "Transplantation is not a scalable, affordable or even safe treatment for HIV patients," Henrich said.

The so-called "Berlin patient," Timothy Brown, is the first documented case of a sterilizing cure for HIV. An American man living in Germany who received a bone marrow transplant for leukemia, Brown has remained HIV-free even after discontinuing his antiretroviral drug therapy. The transplanted bone marrow cells came from a donor who had a rare genetic mutation that increases immunity against the most common form of HIV, and researchers believe that helped protect Brown from re-infection.

In Mississippi, a baby born with HIV nearly three years ago is the first case of a "functional cure," in which early treatment eradicates the virus. Immediate treatment with antiretroviral medications rid the child of all traces of HIV within the first month of life, and she has remained virus-free even after discontinuing drug therapy at 18 months of age.

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Brown Fat Transplants May Spur Weight Loss

Dec. 10, 2012 -- Mice given brown fat transplants lose weight and avoid the kinds of metabolic changes that lead to type 2 diabetes, even on high-fat diets, a new study shows.

Scientists hope the same approach may one day lead to treatments for obesity and diabetes in people.

Unlike white fat, which stores calories, brown fat burns calories like a furnace. Its main job seems to be to keep the body warm.

People have deposits of brown fat between the shoulder blades and along the spine, around the heart, on the side of the neck, and near the collarbones. But those stores are tiny compared to the pounds of white fat most people carry. Researchers have wondered if adding more brown fat might jump-start a body’s sluggish metabolism.

To test that theory, researchers took a tenth of a gram of brown fat from the backs of male mice and injected it into other mice that were the same sex and age.

Scientists have tried brown fat transplants before but they haven’t worked very well, says researcher Laurie J. Goodyear, PhD, head of the Section on Integrative Physiology and Metabolism at Harvard’s Joslin Diabetes Center in Boston.

Goodyear thinks that was partly because of where the brown fat was placed in the body and how long researchers waited to see results.

This time, Goodyear and her team placed the brown fat in the gut, a place it’s not normally found. Studies have shown that fat in the abdomen, especially fat around the liver, influences insulin resistance and also the release of blood fats called triglycerides. 

After eight weeks, mice that got injections of brown fat processed blood sugar more normally, had less insulin resistance, and were leaner than mice given placebo procedures.

“These effects were really very pronounced and very dramatic,” Goodyear says.

Encouraged by their results, the team next gave brown fat transplants to mice on high-fat diets. In both people and mice, high-fat diets reliably lead to weight gain and drive up blood sugar, setting the stage for type 2 diabetes.

Brown fat appeared to blunt some of the effects of the high-fat diet. Transplanted mice maintained their weight and blood sugar better than those who didn’t get transplants. And the more brown fat they got, the stronger the benefits seemed to be.

How is brown fat working? Further testing on transplanted mice showed they had higher levels of proteins and molecules that control how the body handles blood sugar.

The study is published in the Journal of Clinical Investigation.

How soon could the technique be tried in humans?

“I think it’s a ways off,” Goodyear says, “but I think that the studies that we’ve done here really support the idea that it could work.”

Other researchers say the study is interesting, but they aren’t yet convinced that brown fat will someday become a treatment for obesity or diabetes.

“Its purpose is to produce heat and fight cold exposure. It’s certainly not there to combat obesity. It has no purpose in evolution to do that,” says Andre Carpentier, MD, a professor of diabetes and physiology at the University of Sherbrooke in Quebec, Canada.

Carpentier studies brown fat in people, but he was not involved in the current research.

Carpentier says if more studies show that brown fat can safely be increased in the body, it could one day become a tool to fight weight gain and diabetes.

But he says it’s important to keep in mind that even under the best circumstances, the effects of brown fat are likely to be modest.

“You may end up burning a little bit more calories at the end of your day, but it’s not going to be anything close to what you can achieve by doing exercise and diet,” Carpentier says.

View the original article here

Brown Fat Transplants May Spur Weight Loss

ByBrenda Goodman, MA
WebMD Health News Reviewed byLouise Chang, MD

Dec. 10, 2012 -- Mice given brown fat transplants lose weight and avoid the kinds of metabolic changes that lead to type 2 diabetes, even on high-fat diets, a new study shows.

Scientists hope the same approach may one day lead to treatments for obesity and diabetes in people.

Unlike white fat, which stores calories, brown fat burns calories like a furnace. Its main job seems to be to keep the body warm.

People have deposits of brown fat between the shoulder blades and along the spine, around the heart, on the side of the neck, and near the collarbones. But those stores are tiny compared to the pounds of white fat most people carry. Researchers have wondered if adding more brown fat might jump-start a body’s sluggish metabolism.

To test that theory, researchers took a tenth of a gram of brown fat from the backs of male mice and injected it into other mice that were the same sex and age.

Scientists have tried brown fat transplants before but they haven’t worked very well, says researcher Laurie J. Goodyear, PhD, head of the Section on Integrative Physiology and Metabolism at Harvard’s Joslin Diabetes Center in Boston.

Goodyear thinks that was partly because of where the brown fat was placed in the body and how long researchers waited to see results.

This time, Goodyear and her team placed the brown fat in the gut, a place it’s not normally found. Studies have shown that fat in the abdomen, especially fat around the liver, influences insulin resistance and also the release of blood fats called triglycerides. 

'Dramatic Effects'

After eight weeks, mice that got injections of brown fat processed blood sugar more normally, had less insulin resistance, and were leaner than mice given placebo procedures.

“These effects were really very pronounced and very dramatic,” Goodyear says.

Encouraged by their results, the team next gave brown fat transplants to mice on high-fat diets. In both people and mice, high-fat diets reliably lead to weight gain and drive up blood sugar, setting the stage for type 2 diabetes.

Brown fat appeared to blunt some of the effects of the high-fat diet. Transplanted mice maintained their weight and blood sugar better than those who didn’t get transplants. And the more brown fat they got, the stronger the benefits seemed to be.

How is brown fat working? Further testing on transplanted mice showed they had higher levels of proteins and molecules that control how the body handles blood sugar.

The study is published in the Journal of Clinical Investigation.

Human Testing on the Horizon

How soon could the technique be tried in humans?

“I think it’s a ways off,” Goodyear says, “but I think that the studies that we’ve done here really support the idea that it could work.”

Other researchers say the study is interesting, but they aren’t yet convinced that brown fat will someday become a treatment for obesity or diabetes.

“Its purpose is to produce heat and fight cold exposure. It’s certainly not there to combat obesity. It has no purpose in evolution to do that,” says Andre Carpentier, MD, a professor of diabetes and physiology at the University of Sherbrooke in Quebec, Canada.

Carpentier studies brown fat in people, but he was not involved in the current research.

Carpentier says if more studies show that brown fat can safely be increased in the body, it could one day become a tool to fight weight gain and diabetes.

But he says it’s important to keep in mind that even under the best circumstances, the effects of brown fat are likely to be modest.

“You may end up burning a little bit more calories at the end of your day, but it’s not going to be anything close to what you can achieve by doing exercise and diet,” Carpentier says.

View Article Sources

SOURCES:

Stanford, K. Journal of Clinical Investigation, Dec. 10, 2012.

Laurie J. Goodyear, PhD, head, Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard University, Boston.

Andre Carpentier, MD, professor, diabetes and physiology, Montreal Diabetes Research Center, University of Sherbrooke, Quebec, Canada.

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