The gene that causes Duchenne muscular dystrophy can be repaired

The gene that causes Duchenne muscular dystrophy 1), a hereditary disease affecting one in 3500 males, can be repaired according to researchers from Universite Laval’s Faculty of Medicine and the CHUQ Research Center.
Researchers performed in vitro tests by inserting into human muscle cells a variety of meganucleases, enzymes with the ability to correct the dystrophin gene, and also in vivo with mice carrying the mutation that causes the illness. Both series of testing showed that the meganucleases can lead to a restoration of the normal nucleotide sequences of the dystrophin gene and its expression in muscle cells.
A number of hurdles must be overcome before this approach can be tested in humans, cautions Dr. Jacques P. Tremblay who led the team of researchers. “It must first be proven in laboratory animals that it is possible to insert a meganuclease targeting the dystrophin gene directly into muscle cells, and that this will induce the synthesis of dystrophin able to attach to the muscle fiber membrane,” explains the researcher. “We’re still two to three years away from this stage,” he estimates. “Subsequent stages, including human trials, could take even longer,” adds Dr. Tremblay.

1 Duchenne muscular dystrophy is characterized by a rapid progression of muscle degeneration that begins in early childhood leading to loss of ambulation and even death.

source:
healthy feeds.com

Sulforaphane from broccoli can inhibit breast cancer stem cells

Researchers at the University of Michigan Comprehensive Cancer Center studied the effectiveness of sulforaphane¹⁾ in targeting and killing breast cancer stem cells on both mice and cell cultures with promising results.  In the study the sulforaphane extracted from broccoli sprouts prevented new tumors from growing.
“Sulforaphane has been studied previously for its effects on cancer, but this study shows that its benefit is in inhibiting the breast cancer stem cells. This new insight suggests the potential of sulforaphane or broccoli extract to prevent or treat cancer by targeting the critical cancer stem cells,” says Duxin Sun²⁾.
After injecting various concentrations of sulforaphane in mice with breast cancer, researchers measured the number of cancer stem cells in the tumors. The findings showed a decrease in the cancer stem cell population after treatment with sulforaphane, with little effect on the normal cells. Also, the cancer cells from mice treated with sulforaphane were unable to generate new tumors. Similar results were obtained after the researchers tested sulforaphane on human breast cancer cell cultures.
“This research suggests a potential new treatment that could be combined with other compounds to target breast cancer stem cells. Developing treatments that effectively target the cancer stem cell population is essential for improving outcomes,” says Max S. Wicha³⁾.

¹⁾ Sulforaphane is a organosulfur compound obtained from cruciferous vegetables
²⁾ Duxin Sun, Ph.D – study author – is an associate professor of pharmaceutical sciences at the U-M College of Pharmacy and a researcher with the U-M Comprehensive Cancer Center
³⁾ Max S. Wicha, M.D. – study author – is a Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center.

source:
healthy feeds.com

Eating Nuts Daily Lowers Cholesterol

Daily Helping of Nuts May Help Fight Heart Disease, New Study Finds
By Bill Hendrick
WebMD Health News
Reviewed By Laura J. Martin, MD
May 10, 2010 -- Eating nuts on a daily basis improves blood cholesterol levels and reduces the risk of coronary heart disease, a new study says.
Joan Sabaté, MD, DrPH, and colleagues from Loma Linda University in California, pooled data from 25 studies on nut consumption in seven countries, looking at 583 men and women with various cholesterol levels. None was on cholesterol-lowering medications. Nuts evaluated included almonds, hazelnuts, pecans, pistachios, walnuts, macadamia nuts, and peanuts.
Patients in the trials ate an average of 67 grams, or about 2.4 ounces, of nuts daily.
This dietary practice resulted in an average 5.1% reduction in total cholesterol concentration, a 7.4% reduction in LDL or bad cholesterol, and an 8.3% reduction in the ratio of LDL to HDL ("good" cholesterol) levels.
In addition, triglyceride measurements declined by 10.2%, but only among people with initially elevated triglyceride readings. The cholesterol effects of nut consumption were similar in men and women, and were dose related.

Nuts Improve Cholesterol, Heart Health

Different types of nuts had similar effects on blood cholesterol levels, according to the authors. However, "effects of nut consumption were significantly modified by LDL, body mass index, and diet type: the lipid-lowering effects of nut consumption were greatest among subjects with high baseline LDL and with low body mass index and among those consuming Western diets."
The findings support the inclusion of nuts in therapeutic dietary interventions for improving cholesterol levels, the authors say.
"Increasing consumption of nuts as part of an otherwise prudent diet can be expected to favorably affect blood lipid levels (at least in the short term), and have the potential to lower coronary heart disease risk," the authors write.
Nevertheless, moderation is key. Although eating nuts on a regular basis appears to have significant health benefits, nut consumption should be limited to no more than 3 ounces per day because of their high calorie density.
Sabaté and fellow author Emilio Ros, MD, PhD, disclose receiving research funding from the California Walnut Commission, the Almond Board of California, the National Peanut Board, and the International Tree Nut Council. Sabaté has also received an honorarium as a member of the Pistachio Scientific Advisory Board.
The study is published in the May 10 issue of Archives of Internal Medicine.

SOURCES: News release, Archives of Internal Medicine.

Sabate, J. Archives of Internal Medicine, May 10, 2010; vol 170(9).

News release, Loma Linda University, California.

©2010 WebMD, LLC. All Rights Reserved.

source:

medicine net.com

Researchers Discover Genetic Link Between Both Types of ALS

Researchers from Northwestern University Feinberg School of Medicine have discovered a link between sporadic and familial forms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease also known as Lou Gehrig’s disease.

Researchers found that a protein called FUS forms characteristic skein- like cytoplasmic inclusions in spinal motor neurons in most cases of ALS. Mutations in this gene have been previously linked to a small subset of familial ALS cases. Researchers thus linked a rare genetic cause to most cases of ALS, clearing the way for rational therapy based on a known molecular target. The study was recently published online in the Annals of Neurology.

ALS is a disease in which muscle-controlling nerve cells in the brain and spinal cord (motor neurons) die, resulting in rapidly progressive paralysis and death usually within three to five years of the onset of symptoms. Most cases of ALS are of unknown etiology and appear as sporadic ALS. About 5 to 10 percent of ALS cases are familial. Some forms of familial ALS are caused by genetic mutations in specific genes. Mutations in the Cu/Zn superoxide dismutase gene (SOD1) account for approximately 20 percent of familial ALS cases. Mutations in the TAR DNA-binding protein gene (TDP43) and FUS gene occur in about 4 to 5 percent of the familial ALS cases. Altogether, mutations in specific genes have been identified in about 30 percent of familial ALS cases. 

In contrast to familial ALS, the etiology and the pathogenic mechanisms underlying sporadic ALS -- 90 percent of all ALS -- has remained largely unknown. Understanding the causes and pathogenic mechanisms of sporadic ALS is the major challenge in this disease.

For this study, researchers examined the post-mortem spinal cords and brains of 100 cases, 78 with ALS and 22 in a control group. They found FUS pathology in the spinal cords of all the ALS cases, except for a few cases with SOD1 mutations. But FUS pathology was not present in control cases without ALS.

“This is a game changer because it establishes a connection in the development of sporadic ALS with a known cause of familial ALS,” said senior author Teepu Siddique, MD, the Les Turner ALS Foundation/ Herbert C. Wenske Professor of the Ken and Ruth Davee Department of Neurology at Feinberg and a neurologist at Northwestern Memorial Hospital.

“Our finding opens up a new field of investigation for rational therapy for all of ALS,” Siddique added. “This is the holy grail of researchers in this field.”

"There hasn’t been a therapy for most of ALS, because the cause was unknown," Siddique said. “Three genes have been identified in ALS, but the problem has been connecting inherited ALS to sporadic ALS.”

“We identified the FUS pathology in sporadic ALS and most familial ALS cases,” said Han-Xiang Deng, MD, PhD, associate professor of neurology at Feinberg and lead author of the paper. “The patients with the FUS pathology may account for about 90 percent of all ALS cases. Our findings suggest that pathological interaction of FUS with other proteins is a common theme in motor neuron degeneration in the vast majority of the ALS cases. We believe that this is a major step forward in formulating a common pathogenic pathway for motor neuron degeneration. Importantly, it may offer a novel avenue for developing therapies through targeting these FUS-containing inclusions.”

The one exception to the new finding is when familial ALS is associated with a mutation on the SOD1 gene. In those patients and in the mutant SOD1 transgenic mouse models, researchers did not find evidence of FUS pathology.

“This tells us that it follows a different pathway of pathogenesis, so treatment for this form of the disease would have to be different,” Deng said.

The study is supported by the National Institutes of Health, the Les Turner ALS Foundation, the Vena E. Schaff ALS Research Fund, the Harold Post Research Professorship, the Herbert and Florence C. Wenske Foundation, the David C. Asselin MD Memorial Fund and the Les Turner ALS Foundation/Herbert and Florence C. Wenske Professorship.

source:

http://www.feinberg.northwestern.edu

New drug kills non-Hodgkin lymphoma tumor cells

A new type of drug designed to kill non-Hodgkin lymphoma tumor cells has been developed by researchers from the Samuel Waxman Cancer Research Foundation. The new drug targets an oncogene known as BLC6 which functions as a master regulatory protein and also causes the most common form of non-Hodgkin lymphoma.
“It’s a protein that controls the production of thousands of other genes. Because of that, it has a very profound impact on cells and is required for lymphoma cells to survive and multiply,” said Dr. Melnick¹⁾.
Dr. Melnick  and his colleagues were able to identify a “hot spot” on BLC6 that they predicted would play a critical role in protein interactions. They showed that their BCL6 inhibitor drug was specific to BCL6, and did not block other master regulatory proteins. The drug had powerful lymphoma killing activity and yet was non-toxic to normal tissues. “This is the first time a drug of this nature has been designed and it shows that it’s not actually impossible to target factors like BCL6,” he said.

¹⁾ Ari Melnick, M.D. – associate professor of medicine at Weill Cornell Medical College in New York City

Biologists discover how biological clock controls cell division in bacteria

Circadian clock protein KaiC, at the center of the clock, controls the timing of cell division in bacterial colonies around the clock’s periphery. Credit: Guogang Dong, Haitao Guo, John Buchner and Susan Golden








A team of biologists has unraveled the biochemistry of how bacteria so precisely time cell division, a key element in understanding how all organisms from bacteria to humans use their biological clocks to control basic cellular functions.

The discovery, detailed in the February 19 issue of the journal Cell, provides important clues to how the biological clocks of bacteria and other "prokaryotic" cells—which lack cell nuclei—evolved differently from that of "eukaryotic" cells with nuclei that comprise most other forms of life, from fungi to plants and animals.
"A major question in biology is how the circadian clock machinery is different in bacteria than it is in plants, animals and fungi," said Susan Golden, a professor of biology at UC Sana Diego, who headed the study. "We looked at how the biological clock controls when bacterial cells divide—in bacteria, there's a period of four hours where the cells are not allowed to divide—and we identified the structural changes in a key protein that controls this action."
Golden and her colleagues from UCSD, MIT, Michigan State University and Texas A&M University probed cell division in the cyanobacterium Synechococcus elongatus. That organism had been studied extensively by the Golden lab and other researchers, who found that the timing of cell division, patterns of gene expression and compaction of the chromosome are controlled by the circadian clock. What was unknown was precisely how the circadian clock in bacteria controlled cell division.
Using time-lapse microscopy, Golden and her colleagues discovered that the clock proteins KaiA, KaiB, and KaiC in bacteria control the action of a key protein called FtsZ, preventing it from going to the middle of the cell and forming a ring necessary for cell division. After four hours has elapsed, the clock proteins allow FtsZ to move toward the center of the cell and change structurally to form this ring.
"This complex of proteins is at the heart of the bacterial clock controlling cell division," said Golden. "There are two cycles, the cell cycle and the circadian cycle, that need to mesh for organisms to function. What we learned from this study is how these two cycles with different timing periods interact, and that the mechanisms that control the timing of cell division in bacteria are different than they are in eukaryotic cells."
Golden added that knowledge of the mechanisms of how organisms from bacteria to humans control the timing of their cell division and other processes has application to many human problems resulting from disorders in the circadian clock.
"Understanding the basic mechanisms of the biological clock is vital to our daily lives as many people suffer from some problem in their daily sleep cycle," said Golden. "The biological clock in humans plays a central role in whether we gain or lose weight, when we fall asleep and wake up, how likely we are to have accidents and how we respond to disease."

Provided by University of California - San Diego (news : web)
 

Researchers examine link between bacteria in the digestive system and obesity

Obesity is more than a cosmetic concern because it increases a person’s risk for developing high blood pressure, diabetes and many other serious health problems. It’s well understood that consuming more calories than you expend through exercise and daily activities causes weight gain. But with about one in every three American adults now considered obese, researchers are attempting to identify additional factors that affect a person’s tendency to gain and retain excess weight.
In the April issue of Mayo Clinic Proceedings, researchers from Mayo Clinic Arizona and Arizona State University examine the role that bacteria in the human gastrointestinal tract play in regulating weight and the development of obesity.
Known as gut microbiota, the trillions of bacteria that populate the human gastrointestinal tract perform a variety of chores. These “friendly” microbes help extract calories from what we eat, help store these calories for later use, and provide energy and nutrients for the production of new bacteria to continue this work.
According to John DiBaise, M.D., a Mayo Clinic Arizona gastroenterologist and lead author of the Mayo Clinic Proceedings article, several animal studies suggest that gut microbiota are involved in regulating weight and that modifying these bacteria could one day be a treatment option for obesity.
One study cited by the authors observed that young, conventionally-reared mice have a significantly higher body fat content than a laboratory-bred, germ-free strain of mice that lack these bacteria, even though they consumed less food than their germ-free counterparts. When the same research group transplanted gut microbiota from normal mice into germ-free mice, the germ-free mice experienced a 60 percent increase in body fat within two weeks, without any increase in food consumption or obvious differences in energy expenditure.
Another animal study reviewed by the authors focused on the gene content of the gut microbiota in mice. Finding more end products of fermentation and fewer calories in the feces of obese mice led researchers to speculate that the gut microbiota in the obese mice help extract additional calories from ingested food.
“These results suggest that differences exist in the gut microbiota of obese versus lean mice, raising the possibility that the manipulation of gut microbiota could be a useful strategy for regulating energy balance in obese people,” says Dr. DiBaise.
Although information on the link between gut microbiota and obesity in human subjects is more limited, the authors present some evidence supporting this connection. One study cited placed 12 obese participants in a weight-loss program for a year, randomly assigning them to either a fat-restricted or carbohydrate-restricted, low-calorie diet. Researchers noted distinct differences between lean and obese participants when they monitored the type and number of bacteria found in participants’ stool samples before and after the diet changes.
Another study cited followed children from birth to age 7 and analyzed stool samples collected at 6 and 12 months. The children who were normal weight at age 7 had distinctly different bacteria in their samples from those collected from overweight-obese children, suggesting that differences in the composition of the gut microbiota precede overweight-obesity.
Dr. DiBaise says that much more research is needed to clarify a number of issues related to the relationship between the gut microbiota and obesity. Future studies need to establish whether the small changes in caloric extraction seen in recent studies can produce measurable weight differences in humans. Second, researchers need to prove or disprove the possible relationship between the gut microbiota and the regulation of weight.
“In particular, it is essential to demonstrate unequivocally whether differences in gut microbiota in obese versus lean people are the cause or the result of obesity,” says Dr. DiBaise.
Finally, the authors note that the next wave of research should explore the safety and feasibility of modifying the gut microbiota in clinical trials involving humans.
“Although clearly no substitute for proper diet and exercise, manipulation of the gut microbiota may represent a novel approach for treating obesity that has few adverse effects,” says Dr. DiBaise.
Source: Mayo Clinic