Category Archives: Gene Medicine

Sleepless elite ... Margaret Thatcher was said to get by on four hours sleep a night.

Therese Rein once told a journalist that her husband slept about three hours a night.

By this time, Kevin Rudd had already branded himself '24-7 Kevin' and in doing so joined history's long line of short-sleepers: Margaret Thatcher (four hours), Winston Churchill (five), Bill Clinton (five to six), Leonardo Da Vinci (five), Napoleon Bonaparte (three to four), Madonna (four), Silvio Berlusconi (two), P Diddy (less than four), Martha Stewart (two to four) and Donald Trump (three to four).

Some politicians and celebrities have bragged about how little sleep they need - the implication being they are tougher, more productive and more suitable for leadership because of it.

Advertisement: Story continues below

Is there such a thing as a 'sleepless elite' - a segment of the human population that performs equally well on a few hours sleep?

And if so, is Kevin Rudd a genetic freak, or just sleep-deprived like the rest of us?

Two of Australia's leading sleep experts agree that, like all human behaviours, there is variation in how much sleep people need.

And while genes almost certainly play a role, they say, recent newspaper reports that scientists have discovered a "Thatcher gene" are misleading.

"There are some who need less sleep, but scientists cannot explain completely why," Nick Glozier, Associate Professor of Psychological and Sleep Medicine at the University of Sydney, said.

"In terms of how many people are actually these super short sleepers ... about five per cent of the adult population of Australia sleep like that," he said.

Self-reporting of performance after sleep deprivation is unreliable, which makes it difficult to judge how many people fit into this sleepless elite, Professor Glozier said.

"You can't turn around to pilots and surgeons and say, 'How do you think you're doing after this amount of sleep?', because actually they are probably the worst person to ask," Professor Glozier said.

"For instance, if Kevin Rudd says he thinks he's doing well; he probably isn't the best judge of that."

Others may sleep only four hours at night, but compensate by taking power naps during the day, Professor Glozier said.

"If you look at Maggie Thatcher - she had cat naps."

Professor Leon Lack, a sleep expert at Flinders University in South Australia, said that many of history's short-sleepers probably restricted their REM (Rapid Eye Movement) sleep, which, rather than making a person sleepy often has a "manic" or "energising" effect.

"In rats, for example... it results in increased eating behaviour, increased fighting, increased sexual activity.

"One of the effects of REM sleep loss is people become more emotionally labile, which means more emotionally variable. So they will tend to go through more swings, of exhilaration, but also quicker to anger," Professor Lack said.

As for that genetically-blessed minority who can sleep four hours and be sharp and in a good mood; scientists have only a limited understanding of why they are this way.

Scientists in Germany recently found that one gene, called ABCC9, could partly explain why some people seem able to operate on little sleep, but Professor Glozier said if scientists had really discovered a "Thatcher gene" then managers would surely be recruiting for it.

"You can imagine how valuable that [the "Thatcher gene"] might be. If you're going to run some merchant bank where your traders are expected to work 18 hours... I know what I'd be considering."

Continued here:
Quest for a Thatcher gene

Sleepless elite ... Margaret Thatcher was said to get by on four hours sleep a night.

Therese Rein once told a journalist that her husband slept about three hours a night.

By this time, Kevin Rudd had already branded himself '24-7 Kevin' and in doing so joined history's long line of short-sleepers: Margaret Thatcher (four hours), Winston Churchill (five), Bill Clinton (five to six), Leonardo Da Vinci (five), Napoleon Bonaparte (three to four), Madonna (four), Silvio Berlusconi (two), P Diddy (less than four), Martha Stewart (two to four) and Donald Trump (three to four).

Some politicians and celebrities have bragged about how little sleep they need - the implication being they are tougher, more productive and more suitable for leadership because of it.

Advertisement: Story continues below

Is there such a thing as a 'sleepless elite' - a segment of the human population that performs equally well on a few hours sleep?

And if so, is Kevin Rudd a genetic freak, or just sleep-deprived like the rest of us?

Two of Australia's leading sleep experts agree that, like all human behaviours, there is variation in how much sleep people need.

And while genes almost certainly play a role, they say, recent newspaper reports that scientists have discovered a "Thatcher gene" are misleading.

"There are some who need less sleep, but scientists cannot explain completely why," Nick Glozier, Associate Professor of Psychological and Sleep Medicine at the University of Sydney, said.

"In terms of how many people are actually these super short sleepers ... about five per cent of the adult population of Australia sleep like that," he said.

Self-reporting of performance after sleep deprivation is unreliable, which makes it difficult to judge how many people fit into this sleepless elite, Professor Glozier said.

"You can't turn around to pilots and surgeons and say, 'How do you think you're doing after this amount of sleep?', because actually they are probably the worst person to ask," Professor Glozier said.

"For instance, if Kevin Rudd says he thinks he's doing well; he probably isn't the best judge of that."

Others may sleep only four hours at night, but compensate by taking power naps during the day, Professor Glozier said.

"If you look at Maggie Thatcher - she had cat naps."

Professor Leon Lack, a sleep expert at Flinders University in South Australia, said that many of history's short-sleepers probably restricted their REM (Rapid Eye Movement) sleep, which, rather than making a person sleepy often has a "manic" or "energising" effect.

"In rats, for example... it results in increased eating behaviour, increased fighting, increased sexual activity.

"One of the effects of REM sleep loss is people become more emotionally labile, which means more emotionally variable. So they will tend to go through more swings, of exhilaration, but also quicker to anger," Professor Lack said.

As for that genetically-blessed minority who can sleep four hours and be sharp and in a good mood; scientists have only a limited understanding of why they are this way.

Scientists in Germany recently found that one gene, called ABCC9, could partly explain why some people seem able to operate on little sleep, but Professor Glozier said if scientists had really discovered a "Thatcher gene" then managers would surely be recruiting for it.

"You can imagine how valuable that [the "Thatcher gene"] might be. If you're going to run some merchant bank where your traders are expected to work 18 hours... I know what I'd be considering."

Visit link:
Sleepless elite: quest for the Thatcher gene

SUNDAY, Feb. 19 (HealthDay News) -- A new animal study suggests that a genetic mutation could put certain people at higher risk for becoming obese if they eat high-fat diets.

At the moment, the practical uses of the research seem to be limited, but physicians could conceivably test people for the mutation and recommend that they avoid certain kinds of diets, said study co-author Dr. Gozoh Tsujimoto, a professor at Kyoto University's department of genomic drug discovery science in Japan. It may also be possible, Tsujimoto said, to eventually give people drugs to combat the effects of the mutation.

If that happens, there would be "a new avenue for personalized health care," Tsujimoto said.

Scientists have been busy studying genetic links to obesity that could make some people more prone to gain extra weight. Two-thirds of Americans are either overweight or obese, the U.S. Centers for Disease Control and Prevention estimates. Excess pounds contribute to a variety of diseases, including heart disease and cancer.

In the new study, researchers looked at the component of the body's internal communication system that plays a role in the regulation of appetite and the production of fat cells.

The investigators found that mice that didn't have the component were 10 percent fatter than other mice when all were fed a high-fat diet. Mice without the component also developed higher intolerance to glucose.

Research conducted in animals does not always translate into humans, and much more research is needed. However, the researchers found that Europeans with the genetic mutation, known as GPR120, were more likely to be obese.

"Our study for the first time demonstrated the gene responsible for diet-induced obesity," Tsujimoto said.

According to Tsujimoto, more than 3 percent of Europeans have the trait. The next step for researchers is to study its prevalence in Japanese, Korean and Chinese people.

What can be done with the knowledge from the study?

Tsujimoto said physicians could advise people with the trait to avoid high-fat diets. A test is available to detect the trait and it costs about $200 in Japan, Tsujimoto said.

While medications could potentially be developed that would reverse the effects of the genetic trait, there are no such drugs now, Tsujimoto added.

Ruth Loos, director of Genetics of Obesity and Related Metabolic Traits at Mount Sinai School of Medicine in New York City, said "these findings provide another piece of what turns out to be the very large puzzle that describes the causes of obesity."

Consistent findings in mice and humans have put the trait "more firmly on the obesity map and provides a new starting point for more research into the function of this gene," said Loos.

"This is only the beginning of likely many years of research to disentangle the physiological mechanisms that lie behind the link between this gene and obesity risk," she said. "It is only when we understand the physiology and biology better that one can start thinking of developing a drug."

The study appears online Feb. 19 in the journal Nature.

More information

For more on obesity, visit the U.S. National Library of Medicine.

Read more here:
Gene Might Boost Risk for Obesity

The study, published in the international science and medicine journal PLoS One, was led by Winthrop Professor Alan Harvey from UWA's School of Anatomy, Physiology and Human Biology, and Associate Professor Jennifer Rodger, NHMRC Research Fellow in Experimental and Regenerative Neurosciences at UWA's School of Animal Biology.  The research was funded primarily by the WA Neurotrauma Research Program.

Professor Harvey said gene therapy was a relatively new strategy that attempted to help injured brain cells survive and regrow.

"Our previous work has shown that when growth-promoting genes are introduced into injured brain cells for long periods of time (up to nine months), the cells' capacity for survival and regeneration is significantly increased," he said.

"We have now shown that these same neurons have also changed shape in response to persistent over-expression of the growth factors.  Importantly, it is not just neurons containing the introduced growth-promoting gene that are affected, but neighbouring "bystander" neurons."

Professor Harvey said neural morphology was very important in determining how a cell communicated with other cells and formed the circuits that allowed the brain to function.

"Any changes in morphology are therefore likely to alter the way neurons receive and transmit information.  These changes may be beneficial but could also interfere with normal brain circuits, reducing the benefits of improved survival and regeneration."

Professor Harvey said the results were significant for those involved in designing gene therapy-based protocols to treat brain and spinal cord injury and degeneration.

"These new results suggest that we may need to be careful about the types of genes we use in neurotherapy and how long we continue the therapy.  While it may be beneficial for these genes to move around and cause changes in other cells, we need to be able to switch them off once the change has taken place."

Provided by University of Western Australia

Read the original post:
Neurons change shape after gene therapy

CAMBRIDGE, Mass.--(BUSINESS WIRE)--

bluebird bio, a world leader in the development of innovative gene therapies for severe genetic disorders, today announced the appointment of David M. Davidson, M.D., to the role of chief medical officer.

“David brings a wealth of gene therapy, rare disease and clinical drug development expertise to bluebird bio during an exciting time in our company’s growth,” said Nick Leschly, chief executive officer of bluebird bio. “Operationally, David’s deep gene therapy and translational medicine experience will help guide bluebird bio’s clinical development efforts and regulatory strategies. With the addition of David to our team, we are well positioned to maximize the high priority opportunities available to us through our broad product platform.”

Prior to joining bluebird bio, Dr. Davidson served as a senior medical director at Genzyme Corporation where he led clinical research for programs in Phases 1 through 4 across a wide range of therapeutic areas for more than a decade. Most recently, Dr. Davidson was the medical leader for Genzyme’s gene therapy and Pompe disease enzyme replacement therapy programs. In addition to Dr. Davidson’s translational medicine experience, he has also worked on a number of commercial products, including Fabrazyme® and Myozyme®/Lumizyme®, and was integral in crafting the new drug application that resulted in the approval of Welchol®. Prior to Genzyme, Dr. Davidson was a medical director at GelTex Pharmaceuticals. Previously, he completed clinical and research fellowships in infectious diseases at the Harvard Longwood Combined Infectious Diseases Program. Dr. Davidson received a B.A. from Columbia University and his M.D. from New York University School of Medicine. In addition, he completed an internal medicine internship, residency training and an endocrinology research fellowship at the University of Chicago Hospitals.

“bluebird bio’s platform has the potential to be truly transformative,” said Dr. Davidson. “It is rare to be presented with an opportunity to develop a novel, clinically validated platform with promising early proof-of-concept data in two indications that can have such a dramatic effect across a broad set of severe genetic diseases. In the next two years, bluebird looks to have its ALD program well into a Phase 2/3 trial and two other programs nearing completion of Phase 1/2 trials for beta-thalassemia and sickle cell disease. I look forward to this exciting challenge and the potential to have a fundamental and meaningful impact on patients and their families.”

About bluebird bio

bluebird bio is developing innovative gene therapies for severe genetic disorders. At the heart of bluebird bio’s product creation efforts is its broadly applicable gene therapy platform for the development of novel treatments for diseases with few or no clinical options. The company’s novel approach uses stem cells harvested from the patient’s bone marrow into which a healthy version of the disease causing gene is inserted. bluebird bio’s approach represents a true paradigm shift in the treatment of severe genetic diseases by eliminating the potential complications associated with donor cell transplantation and presenting a one-time potentially transformative therapy. bluebird bio has two later stage clinical products in development for childhood cerebral adrenoleukodystrophy (CCALD) and beta-thalassemia/sickle cell anemia. Led by a world-class team, bluebird bio is privately held and backed by top-tier life sciences investors, including Third Rock Ventures, TVM Capital, ARCH Venture Partners, Forbion Capital Partners, Easton Capital and Genzyme Ventures. Its operations are located in Cambridge, Mass. and Paris, France. For more information, please visit http://www.bluebirdbio.com.

Read the original:
bluebird bio Appoints David Davidson, M.D., as Chief Medical Officer

Dilated cardiomyopathy, a common cause of heart failure, can be attributed to defects in any of more than 40 different genes. A new study reveals that defects in the gene that encodes the human body’s largest protein, the muscle protein titin, are responsible for more cases of the disease than are caused by all other known mutations.

In a study of nearly 800 people, researchers found unique mutations that truncate titin in 22% of people with dilated cardiomyopathy. Researchers have had a difficult time learning exactly how Titin mutations lead to the disease because of the high expense and technical difficulty in sequencing the unusually large gene.

“It wasn’t that we weren’t aware that titin caused disease—we were. The problem was that the technology was not sufficiently robust to allow comprehensive analysis of that gene in a large collection of patients.”
Christine E. Seidman

In dilated cardiomyopathy, the heart blows up like a balloon. The stretched-out walls of muscle aren’t able to contract effectively, so the heart starts to fail at its job of pumping blood around the body. Deprived of oxygen and nutrients, the patient gets short of breath easily and retains fluid. Eventually, the only option is a heart transplant.

Dilated cardiomyopathy tends to run in families, so Christine Seidman, a Howard Hughes Medical Institute (HHMI) investigator at Brigham and Women’s Hospital in Boston, and her team have looked for—and found—several genes associated with the disease. But still, “we weren’t getting very far,” she says. Every gene was a step forward, but each gene still only accounted for a small percentage of cases of dilated cardiomyopathy. “We had the sense that maybe we’re missing something,” Seidman says. “We took a step back a few years ago to say, ‘What are we missing?’”

Seidman and her colleagues realized that, over the years, they had found several hints that problems with the titin protein could cause dilated cardiomyopathy. Titin is part of the sarcomere, the unit of muscle that contracts. Titin helps assemble the sarcomere as the heart muscle grows and also plays a role in muscle contractions.

But no one had ever organized a big study on titin. “It wasn’t that we weren’t aware that titin caused disease—we were,” Seidman says. “The problem was that the technology was not sufficiently robust to allow comprehensive analysis of that gene in a large collection of patients.”

The problem, in short, was that titin is enormous and sequencing was expensive. The protein is the longest humans make, some 33,000 amino acids stuck end to end. By comparison, the motor protein myosin has about 2,000 amino acids and Lamin A/C, a nuclear membrane protein that is also associated with dilated cardiomyopathy, only has about 675 amino acids. It was just too expensive to sequence big genes in a big group of people, so researchers had passed it over.

In the last decade, the technology has changed. Next-generation sequencing techniques have made it relatively cheap and easy to sequence long stretches of DNA fast. In a study published February 16, 2012, in The New England Journal of Medicine, Seidman and her colleagues sequenced the gene TTN, which codes for titin, in 312 people with dilated cardiomyopathy. They found 72 mutations that made incomplete forms of titin. Together, these explained about a quarter of the cases of dilated cardiomyopathy that run in families and weren’t caused by something else, like cardiovascular disease. That’s more than all the other genes they’d found put together.

Seidman, her husband Jon Seidman, and their colleagues at Harvard Medical School started out with a smaller group, 92 people with dilated cardiomyopathy who came to Brigham and Women’s Hospital. When they began their study, the team expected to find that TTN was yet another gene that accounted for a small number of cases of the disease. They were shocked by what they found: 28 percent of the people had dramatic mutations in the DNA encoding titin, the kind that mean the protein wouldn’t be fully made.

When they did their initial analysis of that data, Seidman recalls, “we said, ‘this is too good to be true.’ “That’s why we went and got more cohorts.” They then sequenced the TTN gene in 71 people with dilated cardiomyopathy from Imperial College in the UK who had been evaluated for heart transplants—they were, on average, much sicker than the Boston patients—and 149 other people with dilated cardiomyopathy from the University of Colorado and the University of Trieste in Italy. The team also sequenced the gene in 231 people with another form of cardiomyopathy recruited at the Mayo Clinic and 249 controls who did not have cardiomyopathy. Stuart Cook at Imperial College, Luisa Mestroni and Matthew Taylor at the University of Colorado, and Michael Ackerman at the Mayo Clinic led the efforts at the collaborating institutions. The data from that larger analysis confirmed what their initial study had hinted: mutations in the TTN gene are the most common known genetic cause of dilated cardiomyopathy.

Seidman hopes someday doctors will use this information to identify people who are likely to develop dilated cardiomyopathy before they get sick. As sequencing continues to get cheaper, it should eventually be possible for individuals to find out if they have a mutation associated with dilated cardiomyopathy. Then they could start taking drugs that make the heart’s work easier by lowering blood pressure, for example.

As scientists figure out how dilated cardiomyopathy develops, they may also be able to figure out how to keep the heart muscle from changing shape in the first place. Those days are far off, but this research is a step in the right direction, Seidman says. “It allows us to focus on what we don’t know yet,” she says. Discovering the role of mutations in titin is like finding one important piece of a jigsaw puzzle. “There are still a lot more pieces in the box that we need to sort through, but that’s a big deal.”

Continued here:
Researchers Identify New Gene Mutations that Cause Heart Disorder