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General interest items edited by Janice Flahiff

[News item] New Drug Approach Could Lead to Cures for Wide Range of Diseases

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Protein Folding (http://helpfromthedoctor.com/blog/2010/07/27/what-is-a-protein/)

From the 9 December 2013 ScienceDaily article

A team led by a longtime Oregon Health & Science University researcher has demonstrated in mice what could be a revolutionary new technique to cure a wide range of human diseases — from cystic fibrosis to cataracts to Alzheimer’s disease — that are caused by “misfolded” protein molecules

Misfolded protein molecules, caused by gene mutation, are capable of maintaining their function but are misrouted within the cell and can’t work normally, thus causing disease. The OHSU team discovered a way to use small molecules that enter cells, fix the misfolded proteins and allow the proteins to move to the correct place and function normally again.

The researchers were led by P. Michael Conn, Ph.D., who was a senior scientist in reproductive sciences and neuroscience at OHSU’s Oregon National Primate Research Center and professor of physiology and pharmacology, cell biology and development and obstetrics and gynecology at OHSU for the past 19 years. This month, Conn joined Texas Tech University Health Sciences Center as senior vice president for research and associate provost.

The team’s work will be published this week in the early online edition of the Proceedings of the National Academy of Sciences. The work was the culmination of 13 years of work on the process by Conn and Jo Ann Janovick, former senior research associate at the ONPRC who is now also at TTUHSC. Richard R. Behringer, Ph.D., from the University of Texas MD Anderson Cancer Center, M. David Stewart, Ph.D., from the University of Houston, and Douglas Stocco, Ph.D., and Pulak Manna, Ph.D., from the department of biochemistry/microbiology at TTUHSC, also contributed to the work.

Conn and his team perfected the process in mice, curing them of a form of disease that causes males to be unable to father offspring. The identical disease occurs in humans and Conn believes the same concept can work to cure human disease as well.

“The opportunity here is going to be enormous,” said Conn, “because so many human diseases are caused by misfolded proteins. The ability of these drugs — called ‘pharmacoperones’ — to rescue misfolded proteins and return them to normalcy could someday be an underlying cure to a number of diseases. Drugs that act by regulating the trafficking of molecules within cells are a whole new way of thinking about treating disease.”

A wide range of diseases are caused by an accumulation of misfolded proteins. Among the diseases are neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Other diseases include certain types of diabetes, inherited cataracts and cystic fibrosis.

Conn said the next steps will be clinical trials to see whether the same technique can work in humans.

Read the entire article here

December 10, 2013 Posted by | Medical and Health Research News | , , , , , , , , , | Leave a comment

Human Lungs Brush out Intruders

 

From the 23 August 2012 article at ScienceNewsDaily

 A runny nose and a wet cough caused by a cold or an allergy may not feel very good. But human airways rely on sticky mucus to expel foreign matter, including toxic and infectious agents, from the body.Now, a study by Brian Button and colleagues from the University of North Carolina at Chapel Hill, NC, helps to explain how human airways clear such mucus out of the lungs. The findings may give researchers a better understanding of what goes wrong in many human lung diseases, such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) and asthma.

The researchers’ report appears in the 24 August issue of the journalScience.

“The air we breathe isn’t exactly clean, and we take in many dangerous elements with every breath,” explains Michael Rubinstein, a co-author of the Science report. “We need a mechanism to remove all the junk we breathe in, and the way it’s done is with a very sticky gel called mucus that catches these particles and removes them with the help of tiny cilia.”

“The cilia are constantly beating, even while we sleep,” he says. “In a coordinated fashion, they push mucus containing foreign objects out of the lungs, and we either swallow it or spit it out. These cilia even beat for a few hours after we die. If they stopped, we’d be flooded with mucus that provides a fertile breeding ground for bacteria.”

Until now, most researchers have subscribed to a “gel-on-liquid” model of mucus clearance, in which a watery “periciliary” layer acts as a lubricant and separates mucus from epithelial cells that line human airways. But this old explanation fails to explain how mucus remains in its own distinct layer.

“We can’t have a watery layer separating sticky mucus from our cells because there is an osmotic pressure in the mucus that causes it to expand in water,” Rubinstein says. “So what is really keeping the mucus from sticking to our cells?”

The researchers used a combination of imaging techniques to observe a dense meshwork in the periciliary layer of human bronchial epithelial cell cultures. The brush-like layer consists of protective molecules that keep sticky mucus from reaching the cilia and epithelial cells, thus ensuring the normal flow of mucus.

Based on their findings, Button and the other researchers propose a “gel-on-brush” form of mucus clearance in which mucus moves atop a brush-like periciliary layer instead of a watery one. They suggest that this mechanism captures the physics of human mucus clearance more accurately.

“This layer — this brush — seems to be very important for the healthy functioning of human airways,” according to Rubinstein. “It protects cells from sticky mucus, and it creates a second barrier of defense in case viruses or bacteria penetrate through the mucus. They would not penetrate through the brush layer because the brush is denser.”

“We found that there is a specific condition, below which the brush is healthy and cells are happy,” Rubinstein explains. “But above this ideal condition, in diseases like CF or COPD, the brush becomes compressed and actually prevents the normal cilia beating and healthy flow of mucus.”

The researchers explain that, whenever the mucus layer gets too dense, it can crash through the periciliary brush, collapse the cilia and stick to the cell surface.

“The collapse of this brush is what can lead to immobile mucus and result in infection, inflammation and eventually the destruction of lung tissue and the loss of lung function,” says Rubinstein. “But our new model should guide researchers to develop novel therapies to treat lung diseases and provide them with biomarkers to track the effectiveness of those therapies.”

 

 

August 27, 2012 Posted by | Uncategorized | , , , , , | Leave a comment

   

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