Ebola virus has resisted previous attempts at drug treatments, but an antibody cocktail now shows promise for taking down the highly lethal pathogen. Also this week: fat cells sweet on saccharin.
Ebola Shots Save Monkeys
The terrifying Ebola virus can be stopped from killing, recent research shows, but only if treatment is delivered within minutes of infection. Now researchers led by Gary Kobinger, PhD, of Canada's National Microbiology Laboratory in Winnipeg, say a cocktail of antibodies can extend the window of opportunity to prevent death from Ebola.
The monoclonal antibodies bind to different regions of the glycoprotein envelope of the virus, they reported in Science Translational Medicine. The researchers gave two groups of four rhesus macaques a lethal dose of the virus and then injected the antibody cocktail three times over a 3-day period, starting either 24 or 48 hours after infection.
Animals whose treatment started a day after infection all recovered fully, while only two of the four treated after 48 hours survived. The timing, dose, and composition of the treatment all need to be tweaked before it can be used in humans, the researchers noted, but the experiments suggest that monoclonal antibodies are a "promising" option for Ebola therapy.
-- Michael Smith
Fat Cells Sweet On Saccharin
Fat cells appear to have a taste for artificial sweeteners that may make them pack on the lipids, researchers found.
It's been shown that the sweet receptors T1R2 and T1R3, which are expressed on the tongue, are also found in adipose tissue. This may help the cell sense whether there's excess energy to be stored, which may contribute to adiposity.
In several different types of cells, Becky Simon, BS, of the University of Michigan, and colleagues found that putting the artificial sweetener saccharin in the cell environment led to greater adipogenesis.
They found the converse was also true; knocking down these receptors prevented fat cells from getting bigger, even in the presence of saccharin.
Simon and colleagues saw similar results in mouse models: animals that lacked these receptors in their fat cells didn't experience excessive weight gain, even on a high-fat diet.
Presenting the results during a late-breaking session at the recent American Diabetes Association meeting, Simon said that artificial sweeteners appear to have a higher affinity for taste receptors than naturally occurring sugars such as fructose and glucose – a finding that needs further exploration.
-- Kristina Fiore
Statins Heal Cell Damage in Diabetes
The mechanism by which statins benefit diabetics with normal LDL cholesterol levels may be by increasing nitric oxide (NO) release, thereby improving endothelial cell function.
In a diabetic rat model, atorvastatin doubled NO release compared with controls, while also significantly decreasing peroxynitrite, which causes cell death, by 38%, according to R. Preston Mason, PhD, from Brigham and Women's Hospital in Boston, and colleagues.
The ratio of NO to peroxynitrite, an indicator of normal endothelial cell function, increased more than threefold in the diabetic rats, researchers reported at the annual meeting of the American Diabetes Association.
Interestingly, the diabetic rats also saw significant reductions in blood pressure, but no change in glucose control. That result suggests that statins reverse endothelial dysfunction by enhancing nitric oxide activity independent of glucose control, investigators said.
-- Chris Kaiser
Bacteria Ease GI Inflammation
An imbalance of gut bacteria can lead to gastrointestinal inflammation and increase the susceptibility to cancer, including colorectal cancer, a recent study suggested.
Previous research had shown that feeding mice the probiotic bacterium Lactobacillus acidophilus -- engineered to lack a gene for a cell surface molecule called lipoteichoic acid -- protects the animals from induced colitis. So Mansour Mohamadzadeh, PhD, of the University of Florida in Gainesville, and colleagues wanted to see whether the same gene could be involved in the inflammatory responses linked to tumor development.
They found that feeding L. acidophilus missing lipoteichoic acid to mice with pathologic inflammation and precancerous colon polyps reset inflammatory responses, returned the intestinal environment to equilibrium, and caused the polyps to shrink.
"Beyond emphasizing the important role of the gut microbiota in mucosal immune regulation and in cancer initiation and progression, this work demonstrates the reversibility of preneoplasia," the researchers wrote in the Proceedings of the National Academy of Sciences.
"Genetically modified L. acidophilus strains may provide new opportunities for regulating intestinal immunity to protect against pathogenic inflammation and the susceptibility to colon cancer."
-- Todd Neale
Milk Vitamin Does a Metabolism Good
High doses of a form of vitamin B3 known as nicotinamide riboside could protect against the consequences of a high-fat diet, researchers proposed.
The compound -- a cousin of niacin found in small amounts in milk and perhaps other foods -- prevented obesity, boosted muscle performance, and prevented diabetes in mice fed a fatty diet. Supplementation at the high levels required for these effects didn't appear to cause side effects, the researchers reported in Cell Metabolism.
"In animals, the use of nicotinamide riboside offers the health benefits of a low-calorie diet and exercise -- without doing either one," Anthony Sauve, PhD, of Weill Cornell Medical College in New York City, noted in a press release.
What the effect of high doses might be in humans isn't clear yet, but there could be broad benefits, he suggested.
"The bottom line is that nicotinamide riboside improves the function of mitochondria, the cell's energy factories," he said in the press release. "Mitochondrial decline is the hallmark of many diseases associated with aging, such as cancer and neurodegeneration."
-- Crystal Phend
Potential New Target for Diabetes Drugs
Discovery of a new receptor -- dubbed the mitochondrial Target of Thiazolidinediones, or mTOT -- may lead to new drugs for the treatment of type 2 diabetes, researchers reported at the American Diabetes Association meeting.
Thiazolidinediones (TZDs, glitazones) have generally been understood to work through the so-called PPAR-gamma receptor. That action, however, appears to carry risk of serious adverse events -- such as myocardial infarction with rosiglitazone (Avandia) or bladder cancer with pioglitazone (Actos).
The researchers, led by Jerry Colca, PhD, of Metabolic Solutions Development Co. in Kalamazoo, Mich., hope that because mTOT is located in the mitochondria, drugs binding to it will avoid the risky adverse event profile.
Knocking out the mTOT gene in genetically modified mice led to their death in utero. In cell culture, lack of mTOT eliminated drug-enhanced differentiation of brown fat cells, the researchers reported.
On the other hand, activating the mTOT receptor enhanced differentiation of brown adipose tissue cells, which has been shown to offer metabolic advantages.
The company has developed two drugs targeting mTOT now in clinical trials.
-- Cole Petrochko