Cell-specific mechanism-based gene therapy approach to treat retinitis pigmentosa

Cell-specific mechanism-based gene therapy approach to treat retinitis pigmentosa

Friday, September 30, 2011

In a paper published in the October 2011 issue of Experimental Biology and Medicine, a team of researchers at Columbia University Medical Center led by Stephen Tsang, MD, Ph.D have achieved temporary functional preservation of photoreceptors in a mouse model for retinitis pigmentosa (RP) using novel bipartite gene therapy.

RP is a heterogeneous disorder characterized by progressive degeneration of rod photoreceptors (which mediate night vision) causing night blindness and eventually total blindness. About 36,000 cases of simplex and familial RP worldwide are caused by mutant phosphodiesterase (PDE6). Says Dr. Tsang,

"Victor McKusick's Mendelian Inheritance in Man catalog has approximately 4,000 genetic disease entries, but only 4 of these are already curable by gene-therapy approaches. This bipartite vector, which allows cell-specific delivery of both the normal gene and shRNA to knockdown other genes in the pathway, represents a strategy that may help cure many more retinal degenerations. Degeneration of rod photoreceptors also affects approximately 9 million Americans with age-related macular degeneration. Strategies to save photoreceptors in mouse models of RP may be applicable to that disease as well."

In spite of this high prevalence, the interplay between defective PDE metabolism and RP pathogenesis remains poorly understood. In several mouse models for RP, defects in the PDE6B enzyme result in increased levels of the signaling molecules cGMP (mediated by GUCY2E cyclase) and Ca2+ (mediated by the CNGA1 channel).

Several aspects of the EBM report are innovative. It not only tackles the lack of functional PDE6? (by augmenting function with conventional gene replacement), but simultaneously counteracts the central biochemical impact of that lost function by decreasing abnormally accumulated cGMP and Ca2+. Furthermore, they used a tissue-specific promoter to achieve cell-specific expression of the transduced genes, which is unusual for shRNA delivery.

The researchers at Columbia developed three different lentiviral vectors, each of them designed to deliver wild-type Pde6b cDNA and one of two shRNAs. One vector delivered the cDNA and GUCY2E shRNA to reduce cGMP levels; another vector delivered the wild-type cDNA and CNGA1 shRNA to reduce Ca2+ levels; the third delivered the cDNA and the Gucy2e shRNA with a tissue-specific promoter. The bipartite approach was conceived as a way to improve therapeutic efficacy over that of a single-therapy approach, which was tested in an earlier project from Dr. Tsang's lab. While the current project did not show improvement over their previous work, the researchers are optimistic that bipartite delivery may represent an important resource in future explorations of gene therapy in the eye and other tissues types.

Typical existing shRNA vector systems use the RNA polymerase III promoter, which is expressed in essentially all cell types, to drive expression of the transduced gene. However, expression of shRNA targeting GUCY2E in cone photoreceptors, which mediates color vision, would have unwanted and deleterious effects on vision. To achieve rod-specific expression of the shRNA, the researchers in this work embedded Gucy2e shRNA into the Pol II transcription unit of pre-miR34, which is expressed solely in rods. Similar methods can be used to target different tissues, so this method may have wide applicability.

The testing of shRNA therapeutic approaches in Pde6bH620Q mice should facilitate pre-clinical therapeutic evaluation of retinitis pigmentosa. Lessons learned from the proposed studies will eventually be translated into strategies for treatment trials in larger animal models of PDE6? deficiency, such as Irish Setter dogs, before seeing application in human therapeutics.

Dr. Steve Goodman, Editor-in-Chief of Experimental Biology and Medicine said, "Researchers at Columbia University Medical Center led by Stephen Tsang, MD, Ph.D have used a unique gene therapy approach to preserve photoreceptors and prolong functional vision in a mouse model of retinitis pigmentosa (RP). There work offers the promise of a future gene therapy cure for RP".

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Society for Experimental Biology and Medicine: http://www.sebm.org/

Thanks to Society for Experimental Biology and Medicine for this article.

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Source: http://www.labspaces.net/113900/Cell_specific_mechanism_based_gene_therapy_approach_to_treat_retinitis_pigmentosa

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Source: http://www.simprograms.com/35351/ubania-sims-and-9-pets-videos/

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What is Hypnosis? ? Prudent Articles

If you don?t know a good deal about the benefits of hypnotherapy you could be asking oneself, ?what is hypnosis and how does it work?? The definition of hypnosis includes becoming inside a deep mutative state open to ideas from a hypnotist. It really is generally known as a comedy act finding folks to do unusual or silly items whilst they may be in a hypnotic state. Nevertheless, hypnotherapy is actually a broadly utilized strategy to assist relieve persistent pain, conquer addiction, and lose weight and many other medical conditions.

You can find specific actions a hypnotherapist will take a patient by way of in order to total the process. It starts by discussing the concern to be resolved. Once the hypnotherapist has an understanding of the background of the issue, such as a phobia or addiction, they?re able to greater personalize the ideas given for the particular person becoming hypnotized. Then the hypnotherapist assists the particular person unwind into a deep meditative state so they may be a lot more susceptible towards the recommendations provided by the therapist.

The third step is always to dissociate the response the individual has. This may possibly need to have a number of sessions to actually get the suggestions to ?stick? within the persons thoughts. The hypnotherapist will get the particular person to respond inside a complaisant manor to assure they may be inside a deep relaxed state and able to absorb the suggestions getting given to them. The last two methods are coming out from the deep trance like state and discussing the encounter.

Hypnosis can be preformed by anybody. To get therapeutic advantages be sure you get treatment method from a licensed hypnotherapist. These that execute hypnosis as a celebration trick are usually not licensed medical experts. Although you don?t must be a licensed hypnotherapist to hypnotize men and women in the event you want the medical advantages and a trusted specialist it?s important to search out someone with the appropriate qualifications and background.

You?ll be able to also learn self hypnosis to help manage discomfort for persistent illness, kid birth, pain linked with injuries and burns and several other ailments. There are on the internet courses, books accessible and classes you can take to learn diverse strategies. If you want to become licensed using the American Society of Clinical Hypnosis you must have a doctorate in medicine, or even a master?s level degree in nursing, psychology or the like. Exploring hypnosis can open a new world of possibilities. If you?re struggling with an addiction, pain or just need to improve element of the life odds are you can uncover assist via hypnotherapy.

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Source: http://prudentarticles.com/self-improvement/nlp-hypnosis/what-is-hypnosis

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Weight Loss ? Unimaginable Losing Weight the Healthy Way

Almost 110 million Americans were overweight or obese in 2000. Today, obesity continues to be a serious problem and is predicted to reach epidemic levels by the year 2020.

The rise in the number of fast food joints that have a lot of saturated fat in the meals, the use of a lot of refined sugar in sodas and other processed foods and eating food with less fiber have all contributed to the fact that today there are more people than ever before who are classified as either overweight or obese.

Of course, a lot of other factors have contributed to this as well, such as genetics, overeating and the baby boom generation has aged. And the unfortunate fact is that, as you age, your metabolism slows, down making it harder than before to burn the food that you consume.

Controlling your weight and avoiding weight gain as you get older is important for more than cosmetic reasons. Fact is, being overweight or obese takes a huge toll on your physical health. Indeed, if you are more than 20 pounds over your ideal weight, you are at greater risk for a rogues? gallery of potentially deadly conditions, including diabetes, high blood pressure, endometrial cancer, arthritis, obstructive sleep apnea, and breast cancer.

If you have a sedentary lifestyle and are overweight, you are at a higher risk of cardiovascular disease and other heart related problems. And, if you already have a medical condition, such as high cholesterol, being overweight puts you at higher risk for complications, such as hypertension and stroke.

The good news is that even modest amounts of weight loss can improve your health significantly. Loss of 10% of body weight can reduce blood pressure, high cholesterol, triglyceride, and high blood sugar levels.
Better yet, you can try to prevent the weight from creeping on in the first place. How do you do this?

Eat right. Keep moving.

There, you just have read all that you need to know about how to prevent being overweight. Sounds simple enough, doesn?t it?
Unfortunately, about 35% of Americans have trouble adhering to these instructions.

But the plain fact is, it is a whole lot easier to prevent putting on pounds, than it is to try losing them once they are on. And if there is one thing we all know, it is that weight gain is likely to happen if we do not take forward-thinking steps to prevent it.

The good news is that it is never too late to lose weight.
The not so good news is that the vast majority of folks who diet usually stray. They tend to go back to their old eating habits even after they learn to enjoy low-fat eating. They tend to return to sedentary ways even though they enjoy exercising.

So what is the solution? There is no simple solution. And even if there was one, the likelihood is that it wouldn?t deliver lasting results.
The quick weight loss fads that have spread like fire on the market these days do not provide lasting results. More often than not, dieting methods that involve dietary drinks, foods and supplements or pills do not work. And if they do, the results are just temporary.

Fast-track diet programs, as scientific research shows, are only good while they last. Rapid weight loss all too often results in rapid weight gain. People who undergo low carbohydrate or low calorie diets normally revert back to old eating habits, simply because human beings can not actually live on with this type of diet scheme for the rest of their lives.

If you really want to lose weight and KEEP IT OFF you have to be smart about dieting. You have to select a healthy weight loss plan, set realistic goals and NOT expect to lose a lot of pounds in a short span of time.

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Source: http://journalofmedicine.info/weight-loss-unimaginable-losing-weight-the-healthy-way/?utm_source=rss&utm_medium=rss&utm_campaign=weight-loss-unimaginable-losing-weight-the-healthy-way

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Orissa hit by worst floods in 30 years (Reuters)

NEW DELHI (Reuters AlertNet) ? Tens of thousands of people in Orissa are stranded - living on roof tops or sleeping in the open with little food and water - in the worst floods to hit the area in 30 years, aid workers and officials said on Wednesday.

The flooding, sparked by two spells of heavy monsoon rains, has disrupted the lives of more than two million people after submerging over 3,000 villages in the impoverished coastal state. At least 38 people have died.

"This really is the worst flooding in Orissa for at least three decades," John Roche, country head for the International Federation of Red Cross and Red Crescent Societies (IFRC), told AlertNet.

"In a second round of flooding, in just a matter of weeks, the numbers of affected have almost doubled, leaving tens of thousands marooned, and homes across hundreds of villages submerged."

Orissa, one of India's poorest regions located on the Bay of Bengal coast, is prone to natural disasters - often staggering from heatwaves and droughts to cyclones and floods.

A super cyclone in 1999 hit 12 districts, while major floods in 1980 left 13 districts inundated. Government officials say the current floods have hit a much larger area.

"This is the worst since 1980," said Suresh Chandra Suara, Orissa's joint relief commissioner, adding that the disaster has affected 21 of the state's 30 districts.

NORTHERN STATES HIT TOO

India usually experiences monsoon rains from June to September, which are vital for its agriculture. But the rains frequently cause landslides and flooding - displacing hundreds of thousands, devastating homes, destroying crops and triggering illnesses such as diarrhoea.

This year's heavy rains have also taken their toll in Bihar and Uttar Pradesh. An estimated five million people have either been displaced or had their homes, crops or possessions destroyed or damaged.

But aid workers say the situation is most urgent in Orissa's worst-hit districts of Jajpur, Balasore, Bhadrak and Kendrapara where many poor farming communities are marooned with little aid, prompting authorities to air-drop food packets.

In some areas, water levels are 5-6 feet deep and people have made platforms on their roofs for fear of drowning, while others are sleeping out in the open on higher ground.

Cassie Dummett, head of programming for Catholic Relief Services, an international aid agency working in the area, said the emergency response is not yet meeting needs.

"Access to clean water is a serious problem and many people have been forced to drink the contaminated flood waters," she said. "Shelter is also inadequate as people have had their homes destroyed."

(Additional reporting by Jatindra Dash in New Delhi, Alka Pande in Lucknow and an AlertNet correspondent in Patna)

AlertNet is the world's humanitarian news site run by the Thomson Reuters Foundation. For more AlertNet stories, visit www.trust.org/alertnet

Source: http://us.rd.yahoo.com/dailynews/rss/india/*http%3A//news.yahoo.com/s/nm/20110929/india_nm/india596115

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