Category Archives: Gene Medicine

Public release date: 18-Sep-2012 [ | E-mail | Share ]

Contact: Mattias Lorentzon, University of Gothenburg mattias.lorentzon@medic.gu.se 46-031-342-4929 University of Gothenburg

A big international study has identified a special gene that regulates bone density and bone strength. The gene can be used as a risk marker for fractures and opens up opportunities for preventive medicine against fractures. The study, led by the Sahlgrenska Academy, University of Gothenburg, Sweden, was published in the journal PLoS Genetics.

The international study, which involved more than 50 researchers from Europe, North America and Australia and was led by Associate Professor Mattias Lorentzon and Professor Claes Ohlsson at the Sahlgrenska Academy, University of Gothenburg, is based on extensive genetic analyses of the genetic material of 10,000 patients and experimental studies in mice.

Through the combined studies, researchers have succeeded in identifying a special gene, Wnt16, with a strong link to bone density and so-called cortical bone thickness, which is decisive to bone strength.

The genetic variation studied by the international research network could predict, for example, the risk of a forearm fracture in a large patient group of older women.

"In the experimental study, we could then establish that the gene had a crucial effect on the thickness and density of the femur. In mice without the Wnt16 gene, the strength of the femur was up to 61 per cent lower," according to Mattias Lorentzon at the Institute of Medicine, the Sahlgrenska Academy, University of Gothenburg.

The discovery opens up opportunities to develop new medicines to prevent the most common fractures.

"Low cortical bone mass is a decisive factor in, for example, hip and forearm fractures. Unfortunately, the treatments currently used for brittleness of the bones have very little effect on the cortical bone mass," says Mattias Lorentzon.

"If we can learn to stimulate the signaling routes of the Wnt16 gene, we could strengthen the skeleton in these parts too, thereby preventing the most common and serious fractures. The discovery of Wnt16 and its regulation of cortical bone mass is therefore very important," according to Mattias Lorentzon.

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New gene offers hope for preventive medicine against fractures

Newswise A team of scientists from Johns Hopkins and other institutions report that restoring tiny, hair-like structures to defective cells in the olfactory system of mice is enough to restore a lost sense of smell. The results of the experiments were published online last week in Nature Medicine, and are believed to represent the first successful application of gene therapy to restore this function in live mammals.

An expert in olfaction, Randall Reed, Ph.D., professor of molecular biology and genetics and co-director of the Center for Sensory Biology at the Johns Hopkins Institute for Basic Biomedical Sciences, cautions that researchers are still years away from applying the same therapy in people, and that if and when it comes, it will likely be most effective for those who suffer from anosmia (lack of smell) due to inherited genetic disorders. But our work has already contributed to a better understanding of the cellular factors involved in anosmia, and that will give us insights into other neurological disorders, as well, he says.

The mice used in the current study carried a genetic mutation that destroyed the production of a protein critical for the functioning of cilia in the cells responsible for smell, called olfactory sensory neurons. These specialized cells each display several of the protruding, hair-like structures that contain receptors for odorants. Without functional cilia, the cells become a broken link in the chain of events necessary for proper odor detection in the environment, the researchers explained.

Beginning with a common cold virus, which readily infects the cells of the nasal cavity, researchers replaced some of the viral genes with a corrected version of the defective cilia gene. They then infected smelling-impaired mice with the altered virus, delivering the corrected gene to the olfactory neural cells that needed it.

At the cellular level, scientists saw a restoration of proper chemical signaling between nerve cells after the treated mice were stimulated with various odorants. Perhaps even more indicative of their success, Reed says, was the 60 percent increase in body weight that the mice experienced once they could smell their meals, leading to increased appetite. Many people with anosmia lose weight because aromas play a significant part in creating appetite and food enjoyment.

Researchers are optimistic about the broader implications of this work, Reed notes, because cilia are not only important to olfactory cells, but also to cells all over the body, from the kidney to the eye. The fact that they were able to treat live mice with a therapy that restored cilia function in one sensory system suggests that similar techniques could be used to treat cilia disorders elsewhere.

We also hope this stimulates the olfactory research community to look at anosmia caused by other factors, such as head trauma and degenerative diseases, says senior author Jeffrey Martens, Ph.D., an associate professor of pharmacology at the University of Michigan. We know a lot about how this system works now have to look at how to fix it when it malfunctions.

In addition to Randall Reed from Johns Hopkins, the papers authors include Jeffrey Martens, Jeremy McIntyre, Ariell Joiner, Corey Williams, Paul Jenkins, Dyke McEwen, Lian Zhang and John Escobado from the Martens Lab at the University of Michigan; Erica Davis, I-Chun Tsai and Nicholas Katsanis from Duke University; Aniko Sabo, Donna Muzny and Richard Gibbs from the Baylor College of Medicine; Eric Green and James Mullikin from the National Institutes of Health Intramural Sequencing Center; Bradley Yoder from the University of Alabama-Birmingham; Sophie Thomas and Tania Atti-Bitach from LUniversit Paris Descartes; Katarzyna Szymanska and Colin A. Johnson from St. Jamess University Hospital in Leeds, UK; and Philip Beales from University College London, UK.

The study was funded by the National Institutes of Health: National Institute on Deafness and Other Communication Disorders (#R01DC009606, F32DC011990, R01DC004553, R01DC008295), National Institute of Diabetes and Digestive and Kidney Diseases (#R01DK75996, R01DK072301, R01DK075972, DK074083), National Institute of Child Health and Human Development (#R01HD042601), and National Eye Institute (#R01EY021872). Additional funding sources included LAgence Nationale de la Recherche and the European Communitys Seventh Framework Programme.

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The Nose Knows: Gene Therapy Restores Sense of Smell in Mice

04-07-2012 14:06 I created this video with the YouTube Video Editor for our cutting edge science class. Scientific information (or lack thereof) is not necessarily true. No insult was meant by this film. Enjoy!

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The tale of how Simba gets successful GENE THERAPY - Video

04-07-2012 05:11 Conference by Maria Pia Cosma, ICREA Research Professor, leader of the laboratory Reprogramming and Regeneration, within the Gene Regulation, Stem Cells and Cancer research programme, at the Centre for Genomic Regulation, in Barcelona, Spain. Her research group is dedicated to studying the mechanisms that control the reprogramming of adult cells in order to determine whether this reprogramming contributes to tissue regeneration in higher vertebrates (fish, amphibians, birds and mammals). In recent years, there have been numerous studies of how adult cells of our body can be turn back into stem cells (ie those that have the potential to become any type of adult cell). A skin cell, for example, can be "induced" (converted) into a stem cell again, and then be transformed into a cell of another tissue (muscle, nerve, blood, etc.). This has generated great interest in the field of regenerative medicine. For example, this type of cells called "induced pluripotent stem cells" (IPS) can be used in the treatment of many diseases. But is this really possible? What should we keep in mind according to this approach? Scientists have also discovered that the reprogramming of adult cells can occur naturally in the body, but still do not understand why this happens and, more importantly for the purposes of regenerative medicine, how it happens.

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Cellular reprogramming: a real tool of regenerative medicine? - Video

By Brian Alexander

Most people who buy cosmetic lotions and potions know that while the people working behind the department store makeup counters may wear white lab coats, the stuff they sell is more about packaging than science.

But a Northwestern University team is bucking that image, reporting today that theyve created a way to regulate genes affecting the skin -- merely by applying moisturizer.

Not only could their technology pave the way for cosmetics that actually work, but it also might also prove to be a valuable weapon in fighting melanoma, the deadliest form of skin cancer, or diseases like psoriasis, and wounds like the intractable sores that often plague diabetics.

This is a blockbuster in the ways we will treat diseases of the skin, saidChad Mirkin, director of the International Institute for Nanotechnology and the George B. Rathmann Professor of Chemistry at Northwestern said. Were talking about ailments, scarring, wound healing, ways of regulating them or retarding them.

In a research paper published today in the Proceedings of the National Academy of Sciences, Mirkin and his colleagues describe not a drug, exactly, but a way of delivering small sections of nucleic acids (DNA and RNA are nucleic acids) called short interfering RNA, or siRNA, to cells. The cells take up the siRNA, which then alters the way a gene inside each cell can be read by the protein-making system.

The team used gold particles with a diameter of 13 nanometers. (One nanometer is 1-billionth of a meter. A typical strand of human hair is roughly 60,000 nanometers wide.) They coated the particles with siRNA to create what they call spherical nucleic acid nanoparticleconjugates, or SNAs. Millions of SNAs were then added to a commercially available petroleum-based skin moisturizer and the mixture was applied to mice and to lab-grown human skin.

In their key experiment in mice, they used their new system to tamp down the activity of a gene called epidermal growth factor receptor, or EGFR, thats involved in the growth of melanoma. As its name implies, EGFR receives messages from the epidermal growth factor protein. So toning down EGFR will interrupt the message; growth will be reduced or stop.

After mice were treated with the mixture three times per week for three weeks, the expression of the EGFR gene was reduced by 65 percent.

'Impressive' resultsSteve Dowdy, professor of cellular and molecular medicine at the University of California San Diego, and a Howard Hughes Medical Institute investigator specializing in RNA inhibition and ways to deliver siRNAs, called that result impressive.

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Gene healing in a lotion? Researchers are close

ScienceDaily (July 2, 2012) Getting under your skin takes on a brave new meaning thanks to Northwestern University research that could transform gene regulation.

A team led by a physician-scientist and a chemist -- from the fields of dermatology and nanotechnology -- is the first to demonstrate the use of commercial moisturizers to deliver gene regulation technology that has great potential for life-saving therapies for skin cancers.

The topical delivery of gene regulation technology to cells deep in the skin is extremely difficult because of the formidable defenses skin provides for the body. The Northwestern approach takes advantage of drugs consisting of novel spherical arrangements of nucleic acids. These structures, each about 1,000 times smaller than the diameter of a human hair, have the unique ability to recruit and bind to natural proteins that allow them to traverse the skin and enter cells.

Applied directly to the skin, the drug penetrates all of the skins layers and can selectively target disease-causing genes while sparing normal genes. Once in cells, the drug simply flips the switch of the troublesome genes to off.

A detailed study of a method that could dramatically redefine the field of gene regulation will be published online during the week of July 2 by the Proceedings of the National Academy of Sciences (PNAS).

Early targets of the novel treatment are melanoma and squamous cell carcinoma (two of the most common types of skin cancer), the common inflammatory skin disorder psoriasis, diabetic wound healing and a rare genetic skin disorder that has no effective treatment (epidermolytic ichthyosis). Other targets could even include wrinkles that come with aging skin.

The technology developed by my collaborator Chad Mirkin and his lab is incredibly exciting because it can break through the skin barrier, said co-senior author Amy S. Paller, M.D., the Walter J. Hamlin Professor, chair of dermatology and professor of pediatrics at Northwestern University Feinberg School of Medicine. She also is director of Northwesterns Skin Disease Research Center.

This allows us to treat a skin problem precisely where it is manifesting -- on the skin, she said. We can target our therapy to the drivers of disease, at a level so minute that it can distinguish mutant genes from normal genes. Risks are minimized, and side effects have not been seen to date in our human skin and mouse models.

A co-senior author of the paper, Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering. He also is the director of Northwesterns International Institute for Nanotechnology.

Mirkin first developed the nanostructure platform used in this study in 1996 at Northwestern, and the FDA-cleared technology now is the basis of powerful commercialized medical diagnostic tools. This, however, is the first realization that the nanostructures naturally enter skin and that they can deliver a large payload of therapeutics.

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Breaking the skin barrier: Drugs topically deliver gene therapy via commercial moisturizers for skin disease treatment