Researchers Develop Novel Wound-Healing Technology

Tue, 11/29/2016 - 2:10pm by Washington State University A WSU research team has successfully used a mild electric current to take on and beat drug-resistant bacterial infections, a technology that may eventually be used to treat chronic wound infections. The researchers report on their work in the online edition of npj Biofilms and Microbiomes. Led by Haluk Beyenal, Paul Hohenschuh Distinguished Professor in the Gene and Linda Voiland School of Chemical Engineering and Bioengineering, the research team used an antibiotic in combination with the electric current to kill all of the highly persistent Pseudomonas aeruginosa PAO1 bacteria in their samples. The bacteria is responsible for chronic and serious infections in people with lung diseases, such as cystic fibrosis, and in chronic wounds. It also often causes pneumonia for people who are on ventilators and infections in burn victims. "I didn't believe it. Killing most of the persister cells was unexpected," said Beyenal, when he first saw the results. "Then we replicated it many, many times." Bacterial resistance is a growing problem around the world. While antibiotics were a miracle drug of the 20th century, their widespread use has led to drug-resistant strains. In the U.S. at least two million infections and 23,000 deaths are now attributable to antibiotic-resistant bacteria each year, according to the Centers for Disease Control. When doctors use antibiotics to treat a bacterial infection, many of the bacteria die. Bacteria that form a slime layer (called a biofilm), however, are more difficult to kill because antibiotics only partially penetrate this protective layer. Subpopulations of "persister" cells survive treatment and are able to grow and multiply, resulting in chronic infections. In the new study, the researchers used an "e-scaffold," a sort of electronic band-aid made out of conductive carbon fabric, along [...]

Scientists find way to create human stem cells with only 23 chromosomes, could revolutionize genetic research

BY DENIS SLATTERY, NEW YORK DAILY NEWS, Wednesday, March 16, 2016, 8:53 PM A scientific discovery unveiled Wednesday could revolutionize genetic research with new screening tools and therapies. Researchers from Columbia University Medical Center, the New York Stem Cell Foundation Research Institute and Hebrew University have found a way to create human stem cells with only 23 chromosomes, rather than the usual 46. Normally, cells with only 23 chromosomes, known as haploid cells, cannot divide on their own. Most cells in the body contain information in the form of DNA, packaged into two sets of chromosomes — one from each parent, called diploid cells. The haploid cells found in the study can be turned into any tissue in the human body, despite only containing one set of chromosomes. The discovery holds promise for therapies to treat a range of conditions, including cancer and infertility, and may even explain why humans reproduce sexually via two parents rather than one. It will allow researchers to study genetic mutations without the “interference” of the second set and help scientists discover how genes mutate and cause devastating diseases like cystic fibrosis, muscular dystrophy and Down syndrome. The study was published in the journal Nature.

Engineering a permanent solution to genetic diseases

Aug. 10, 2015 - In his mind, Basil Hubbard can already picture a new world of therapeutic treatments for millions of patients just over the horizon. It’s a future in which diseases like muscular dystrophy, cystic fibrosis and many others are treated permanently through the science of genome engineering. Thanks to his latest work, Hubbard is bringing that future closer to reality. Basil Hubbard Photo Hubbard’s research, published in the journal Nature Methods ("Continuous directed evolution of DNA-binding proteins to improve TALEN specificity"), demonstrates a new technology advancing the field of genome engineering. The method significantly improves the ability of scientists to target specific faulty genes, and then “edit” them, replacing the damaged genetic code with healthy DNA. “There is a trend in the scientific community to develop therapeutics in a more rational fashion, rather than just relying on traditional chemical screens,” says Hubbard, an assistant professor of pharmacology in the University of Alberta’s Faculty of Medicine & Dentistry. “We’re moving towards a very logical type of treatment for genetic diseases, where we can actually say, ‘Your disease is caused by a mutation in gene X, and we’re going to correct this mutation to treat it’. “In theory, genome engineering will eventually allow us to permanently cure genetic diseases by editing the specific faulty gene(s).” Revolutionizing health care Genome engineering involves the targeted, specific modification of an organism’s genetic information. Much like how a computer programmer edits computer code, scientists could one day replace a person’s broken or unhealthy genes with healthy ones through the use of sequence-specific DNA binding proteins attached to DNA-editing tools. The field has made large strides over the last two decades and may one day revolutionize medical care. One of [...]

Gene therapy for cystic fibrosis shows encouraging results

July 3, 2015 A therapy that replaces the faulty gene responsible for cystic fibrosis in patients' lungs has produced encouraging results in a major UK trial. The study was carried out by the UK Cystic Fibrosis Gene Therapy Consortium, a group of scientists and clinical teams from Imperial College London, the Universities of Oxford and Edinburgh. It involved 116 patients aged 12 and over who received monthly doses of either the therapy or the placebo for one year. Patients who received therapy showed a significant but modest benefit in lung function compared with those receiving a placebo. The trial is the first to show that repeated doses of gene therapy can have a meaningful effect on the disease, and change the lung function of patients. However, the team say more research is needed to improve the effectiveness before the therapy will be suitable for clinical use. Cystic fibrosis (CF) is the commonest lethal inherited disease in the UK, affecting around 10,000 people nationally and over 90,000 worldwide. Patients' lungs become filled with thick sticky mucus and they are vulnerable to recurrent chest infections, which eventually destroy the lungs. The trial, conducted in London and Edinburgh, compared the effects of inhaled gene therapy and a placebo on patients with CF aged 12 and over. Lung function was assessed using a common method of measuring the volume of air a patient can forcibly exhale in one second. Over the course of a year, patients were given 12 treatments at monthly intervals. The results, published in The Lancet Respiratory Medicine, showed that at the end of the trial lung function was 3.7% better in patients who received the 'active' treatment. Participants with the worst lung function at the [...]

Targeting Cystic Fibrosis: Are Two Drugs Better than One?

Posted on May 26, 2015 by Dr. Francis Collins To explain the many challenges involved in turning scientific discoveries into treatments and cures, I often say, “Research is not a 100-yard dash, it’s a marathon.” Perhaps there is no better example of this than cystic fibrosis (CF). Back in 1989, I co-led the team that identified the cystic fibrosis transmembrane conductance regulator (CFTR) gene—the gene responsible for this life-shortening, inherited disease that affects some 70,000 people worldwide [1]. Yet, it has taken more than 25 years of additional basic, translational, and clinical research to reach the point where we are today: seeing the emergence of precise combination drug therapy that may help about half of all people with CF. CF is a recessive disease—that is, affected individuals have a misspelling of both copies of CFTR, one inherited from each parent; the parents are asymptomatic carriers. The first major advance in designer drug treatment for CF came in 2012, when the Food and Drug Administration (FDA) approved ivacaftor (Kalydeco™), the first drug to target specifically CF’s underlying molecular cause [2]. Exciting news, but the rub was that ivacaftor was expected to help only about 4 percent of CF patients—those who carry a copy of the relatively rare G551D mutation (that means a normal glycine at position 551 in the 1480 amino acid protein has been changed to aspartic acid) in CFTR.What could be done for the roughly 50 percent of CF patients who carry two copies of the far more common F508del mutation (that means a phenylalanine at position 508 is missing)? New findings show one answer may be to team ivacaftor with an experimental drug called lumacaftor. Reporting in The New England Journal of Medicine, [...]

Key Component in Protein that Causes Cystic Fibrosis Identified

In a study recently published in PNAS, a National Academy of Sciences journal, a team of cystic fibrosis researchers led by Tzyh-Chang Hwang, PhD, demonstrate how they identified a key mechanism that could influence the behavior of the CFTR protein and flow of chloride ions in and out of cells through the protein. Chloride is a key ingredient in salt, and people with cystic fibrosis have an imbalance of salt caused by the defective CFTR protein. Findings may lay foundation for the development of medications Nearly 70,000 people worldwide are living with cystic fibrosis, a life-threatening genetic disease. There currently is no cure for the condition, but researchers from the University of Missouri have identified a key component in the protein that causes the disease. It is a finding that may lay the foundation for the development of new medications and improved therapies. “We know that cystic fibrosis is caused by mutations in a gene called CFTR, but we don’t know exactly how these mutations affect the function of the CFTR protein,” said Tzyh-Chang Hwang, PhD, professor of medical pharmacology and physiology at the MU School of Medicine and lead author of the study. “In fact, there are nearly 2,000 mutations that could occur in the protein. However, our study identified two amino acids in the CFTR protein that serve as a sort of gate. This gate is a key factor in regulating the flow of chloride ions — one of the key ingredients in salt — into and out of the cells through the CFTR protein.” People with cystic fibrosis have an imbalance of salt in their bodies caused by the defective CFTR protein. Because there is too little salt and water on the [...]

Regenerative Medicine Study Underscores Lung Regeneration Capacity

April 28, 2015, Reid D'Amoco In diseases like cystic fibrosis, the lungs undergo constant healing and remodeling due to chronic infections. To better understand the repair mechanisms the lungs go through in diseases like CF and COPD, scientists have paid great attention to studying cellular regeneration. Scientists at the University of Pennsylvania and Duke University have discovered that mature lung cells have the ability to repair and differentiate into other types of cells found in the lungs. The primary author, Dr. Rajan Jain, published his findings earlier this month in Nature Communications. Type I cells in the lungs are responsible for the exchange of oxygen and carbon dioxide that occurs during breathing, and type II cells are responsible for secreting surfactants. Pulmonary surfactants are critical to lung function; they prevent drying of the airways, and allow the lungs to expand and contract with each breath. Studies performed in the 1960s and 1970s suggest that type II cells have the ability to regenerate into type I cells in the presence of damage, but Dr. Jain and his team have discovered that type I cells can also give rise to type II cells. These findings suggest that the lungs have much more flexible repairing mechanisms than previously thought. By exploring these mechanisms in greater detail, researchers can begin to understand how these mature lung cells already present within the body can be used to treat lung damage caused by diseases like CF. In lung diseases like cystic fibrosis and COPD, there is no cure, and patients only control their conditions through medications and treatments. By learning how to influence the lung’s ability to regrow or repair damaged tissue, the course of treatments for those with CF would drastically change. [...]

Scientists grow ‘mini-lungs’ to aid the study of cystic fibrosis

Scientists at the University of Cambridge have successfully created ‘mini-lungs’ using stem cells derived from skin cells of patients with cystic fibrosis, and have shown that these can be used to test potential new drugs for this debilitating lung disease. We can use these 'mini-lungs' to learn more about key aspects of serious diseases – in our case, cystic fibrosis _Nick Hannan The research is one of a number of studies that have used stem cells – the body’s master cells – to grow ‘organoids’, 3D clusters of cells that mimic the behaviour and function of specific organs within the body. Other recent examples have been ‘mini-brains’ to study Alzheimer’s disease and ‘mini-livers’ to model liver disease. Scientists use the technique to model how diseases occur and to screen for potential drugs; they are an alternative to the use of animals in research. Cystic fibrosis is a monogenic condition – in other words, it is caused by a single genetic mutation in patients, though in some cases the mutation responsible may differ between patients. One of the main features of cystic fibrosis is the lungs become overwhelmed with thickened mucus causing difficulty breathing and increasing the incidence of respiratory infection. Although patients have a shorter than average lifespan, advances in treatment mean the outlook has improved significantly in recent years. Researchers at the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute used skin cells from patients with the most common form of cystic fibrosis caused by a mutation in the CFTR gene referred to as the delta-F508 mutation. Approximately three in four cystic fibrosis patients in the UK have this particular mutation. They then reprogrammed the skin cells to an induced pluripotent state, the state [...]

Study sheds new light on asthma, COPD

March 17, 2015 By Julia Evangelou Strait Z. YURTSEVER When exposed to the protein CLCA1 (red), human cells start to express the chloride ion channel TMEM16A (green) on their surface. New research at Washington University suggests this protein and channel may work together in the over-production of mucus characteristic of diseases such as asthma and chronic obstructive pulmonary disease (COPD). In diseases such as asthma and chronic obstructive pulmonary disease (COPD), the body produces too much mucus, making breathing difficult. New research from Washington University School of Medicine in St. Louis provides clues to potentially counteract inappropriate mucus production. “The new study lays the groundwork for developing treatments for diseases such as asthma, COPD, cystic fibrosis and even certain cancers,” said senior author Thomas J. Brett, PhD, assistant professor of medicine. “It also solves a 20-year mystery about the role of a protein that has long been associated with these diseases.” The study appears March 17 in the journal eLife. About two decades ago, the protein CLCA1 was identified. High levels of CLCA1 in cells lining the airway have long been linked with an overproduction of mucus. Studies at the time suggested CLCA1 was an ion channel, a small opening in the cell membrane that allows charged particles to flow into or out of the cell. CLCA1 was labeled a chloride channel because it appeared to be moving chloride ions across the cell membrane. In general, the movement of different ions into and out of cells govern many important processes from mucus production, to heart rhythms to brain function. “Originally, CLCA1 was misidentified as a chloride channel,” Brett said. “When cells express CLCA1, they produce chloride currents. But as we became better at understanding the [...]

Mucus is Retained in Cystic Fibrosis Patients’ Cells, Leads to Potentially Deadly Infections

Feb. 18, 2015 By: Nathan Hurst COLUMBIA, Mo. – Cystic fibrosis is a genetic disorder that affects one out of every 3,000 children in populations of Northern European descent. One of the key signs of cystic fibrosis is that mucus lining the lungs, pancreas and other organs is too sticky, which makes it difficult for the organs to work properly and, in the lungs, attracts bacteria and viruses resulting in chronic infections. Researchers at the University of Missouri recently found that cystic fibrosis mucus actually gets stuck inside some of the cells that create it, rather than simply becoming stuck on the outside linings of organs. Lane Clarke, a professor of biomedical sciences in the MU College of Veterinary Medicine, says that now that it is better understood how mucus becomes trapped in the body, scientists can begin working on potential treatments for patients with cystic fibrosis that help cells remove the sticky mucus more quickly. “Normally, special cells create mucus and easily push it out to the linings of the organs where it belongs,” said Clarke, who also is a Dalton Investigator in the MU Dalton Cardiovascular Research Center. “However, in cystic fibrosis patients, some cells that create the mucus fail to completely release the mucus, so the mucus becomes stuck halfway in and halfway out.  This makes mucus clearance more difficult and potentially would allow bacteria to have an easy pathway to infecting cells to cause diseases like pneumonia.” Clarke also examined the characteristics of mucus stored within the cells and found that it is not as acidic as in normal cells. “Previously, cystic fibrosis researchers disagreed as to whether cystic fibrosis cells also have a defect in properly acidifying areas inside cells,” Clarke [...]