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Stem Cells to Cure Blindness?

Posted by jase on November 27, 2009

People suffering from a form of incurable blindness could soon become the first patients in the world to benefit from a new and controversial transplant operation using stem cells derived from spare human embryos left over from IVF treatment. 

 Scientists working for an American biotechnology company yesterday applied for a licence to carry out a clinical trial on patients in the US suffering from a type of macular degeneration, which causes gradual loss of vision. They expect the transplant operations to begin early in the new year. 

The development is highly controversial because many “pro-life” groups are opposed to using human embryos in any kind of medical research but scientists believe that the benefits could revolutionise the treatment of many incurable disorders ranging from Parkinson’s to heart disease.

The company has applied for a licence from the US Food and Drug Administration (FDA) and is confident of its application being granted. 

“We’ve seen absolutely no adverse effects whatsoever in any of the preclinical experiments and our cells are more than 99.9 per cent pure,” said Dr Robert Lanza, the chief scientific officer of Advanced Cell Technology (ACT) in Worcester, Massachusetts. 

“We certainly expect them [the FDA] to come back with comments and questions but our hope is that we will start sometime early next year. We’re optimistic and certainly confident in our own data. We’ve been in dialogue [with the FDA] and we know what was on their mind and what they wanted us to do,” he said. “We’re hoping, assuming no hitches, to begin early next year, perhaps March.” 

Stem cells derived from human embryos that are only a few days old have the ability to develop into any of the scores of specialised tissues of the body. The hope is that they could be used to repair the damaged organs and tissues of patients with a relatively simple transplant procedure. 

ACT has filed an “investigational new drug” application with the FDA to treat a form of progressive damage to the retina of the eye called Stargardt’s macular degeneration, which destroys the central part of the retina involved in recognising faces and reading words on a page. They also intend to follow this with an application to treat age-related macular degeneration, which affects more than 500,000 people in Britain and is the most common cause of blindness. 

“We hope to file a second application for age-related macular degeneration very soon within the next few months,” said Dr Lanza. “I think we’ve put together a pretty convincing case but the FDA has to be pretty careful. I’m sure they will come back to us in the next 30 days with more questions.” 

The treatment for eye disease uses stem cells to recreate a type of cell in the retina that supports the photoreceptors needed for vision. These cells form the retinal pigment epithelium – which keep the light-sensing cells of the retina alive – which are often the first to die off in macular degeneration, which in turn leads to loss of vision, he said. 

A single cell from a human embryo left over from IVF treatment was used in the creation of the stem cell “line” that Dr Lanza and his colleagues cultivated in the laboratory. By bathing the stem cells in a suite of chemical messengers, they were able to stimulate them to develop into fully mature retinal pigment epithelium cells. 

Tests on animals found that transplants of the human cells into rats with macular degeneration resulted in a “100 per cent improvement” in vision with no side-effects, Dr Lanza said. Transplants into the 12 human volunteers chosen as guinea pigs for the first clinical trial will involve giving them mild immuno-suppressant drugs to prevent tissue rejection. 

“We’re going to take a precautionary approach and use low-dose immuno-suppression after the operation and after six weeks we’ll taper it off. We don’t know whether we will really need it,” Dr Lanza said. 

He said the clinical trial could well be the first in the world because the only other company that had received a licence from the FDA had had to delay the start of its own clinical trial until the end of next year. 

Geron, which received its FDA licence earlier this year, has run into safety problems with experiments on animals involving the growth of cysts. It has had to provide further information to the FDA in order to satisfy nervous regulators that the new technique is as safe as possible. 

Meanwhile, ACT believes it has stolen a march on Geron because its own pre-clinical studies on animals have shown that its embryonic stem cells are extremely pure and safe with no signs of the cysts seen in the animals injected with the embryonic stem cells that Geron was hoping to use in patients suffering from spinal cord injuries. “They’ve been through this with Geron and the company has put out an announcement that they won’t start until the third quarter of next year, so ours may well be the first trial,” Dr Lanza said.

A similar proposal to treat age-related macular degeneration with embryonic stem cells is being developed by scientists in Britain led by Professor Pete Coffey of University College London, but this clinical trial is unlikely to start until early 2011. “It’s such a complex, wholly new process that nobody had done before and it has to be done properly,” he said. 

“It hasn’t been done before in humans and that is affecting the last stages of the plan to get into the clinic so it’s obvious that we don’t want anything to go wrong. But someone has to be the first take that step.” 

Dr Lanza said that extensive work had been done to ensure that the cells derived from embryonic stem cells were of high enough quality to be considered clinical grade. His company has submitted nine volumes of safety data to the FDA to address concerns over purity and the possibility that the stem cells may trigger the formation of cancerous tumours. 

“What we definitely have going for us is that the cells are so well purified, well characterised and there are no adverse effects. So there is nothing here to send up a flag of concern,” Dr Lanza said. “It has been over a decade since human embryonic stem cells were first discovered. The field desperately needs a big clinical success.”

“After years of research and political debate, we’re finally on the verge of showing the potential clinical value of embryonic stem cells. Our research clearly shows that stem cell-derived retinal cells can rescue visual function in animals that otherwise would have gone blind.

 “We are hopeful that the cells will be similarly efficacious in patients,” Dr Lanza added.

Posted in Biology, DNA, Medical, Science | Tagged: , , , , | 3 Comments »

Dog Hair May Provide Insight on Cancer

Posted by jase on August 27, 2009

Scientists have located the genes that make a poodle’s hair curly, and a collie’s hair long and straight.

No, this wasn’t just a way to ease the boredom of laboratory work, but part of a long-term project to figure out how genes cause disease.

The coats of domestic dogs vary widely — they can be long, short, straight, wavy, curly, wiry, smooth or a combination of different varieties. And that difference is exactly why cancer geneticist Elaine Ostrander decided to study dog hair.

Ostrander, who works at the National Human Genome Research Institute, wanted to know how genes create all this variety. So she studied about 1,000 dogs from about 90 different breeds.

She searched dog DNA the way a chef might compare recipes for souffle. What changed ingredient makes one different from the next? What mutation gives an Airedale terrier his curls and a golden retriever her tresses?

A Three-Gene Recipe

What Ostrander and her team discovered was that only three genes control all the different kinds of dog hair.

“You can go to the dog park, and every breed of dog looks different from every other breed, it seems,” says Ostrander. “Yet, you know, when we get down to the molecular biology, we really find that it’s a combination of three different genes that accounts for all that variation.”

This also has value in studying disease. Human and dog cancers are similar, so the fact that only three genes can create so much variation in hair might provide clues to how genes cause so many cancers in dogs and humans.

“Whether or not the exact same gene is mutated in humans doesn’t really matter,” says Ostrander. “It’s telling us the pathways that are involved, the kinds of genes that are involved, and the kinds of changes in those genes that lead to those diseases.”

The research appears online Thursday in Science Express.

Source: NPR

Posted in Animals, Biology, DNA, Science | Tagged: , , , , , | Leave a Comment »

How Fast Can a Human Possibly Run?

Posted by jase on August 16, 2009

Amazing as Usain Bolt’s new world record 100-meter victory was, his time of 9.58 seconds is nowhere near what biostatisticians such as Peter Weyand of SMU thinks is the natural limit for the human body. Experts studying the steady progression of records over the past 50 years, see the limit of the world record, with a probable error of 0.17 seconds, namely, to lie between 9.26 to 9.60 seconds. Some see 5.0 seconds a possibility.

Because 6′ 5″ Usian Bolt broke the mathematical model that had fit 100-meter record data for almost a century, his incredible performance has reset the bar for how fast researchers believe humans ultimately can run. Will it be done by a 6′ 9″  or 7′ future version of Bolt?

 

How fast will man eventually run? Will he ever run the 100 meters in five seconds flat?

“Not impossible,” says one of the world’s best known authorities on physiology and biomechanics. Professor Peter Weyand, of Southern Methodist University, known for his expertise in terrestrial locomotion and human and animal performance. Weyand said that humans would soon have the ”ability to modify and greatly enhance muscle fibre strength.” This is would actually reduce the difference between the muscle properties of humans and the world’s fastest animal, the cheetah, to almost zero.

Usain Bolt has now brought up the question — will man get faster and faster? And based on what Weyand says, will he one day outrun the cheetah?

“Probably not,” said Weyand. “The same laws of physics apply to all runners. However, biologically speaking, speed is conferred by an ability of the limbs to hit the ground forcefully in relation to the body’s weight, an attribute conferred largely by the properties of the muscles of the runner. The fast four-legged runners or quadrupeds do seem to be advantaged versus bipeds in terms of the mechanics allowed by their anatomy. These mechanics help quadrupeds to get the most out of the muscles that they have in a way that bipedal runners probably cannot.

Scientists believe man can’t run faster than 30 mph, with the best at about 27mph. A cheetah, on the other hand, reaches speeds triple that. Weyand said he expected speed to continue to improve and faster runners to emerge.

Reza Noubary, a mathematician at Bloomsburg University of Pennsylvania and author of a textbook on statistics and sports, had previously calculated an “ultimate record” of 9.44 seconds for the 100 meter.

Mathematicians don’t use the body’s physiology to assess human physical limits. They were merely working with data that suggested that human speed increases were decelerating and would eventually stop completely. Indeed, in some events, like the long jump, the pace of record-setting has slowed nearly to a stop. That record has only been broken twice since 1968.

Despite the success of Mureika’s model, Weyand, said that mathematical models could never predict how fast humans might eventually run.

“Predicting it is fine for the sake of kicks, but it’s not a scientifically valid approach,” Weyand said. “You have to assume that everything that has happened in the past will continue in the future.”

He suggested that it’s impossible for mathematicians to predict the magnitude of the “freakiness of athletic talent at the extreme margins of humanity. Bolt, it turns out, is a perfect example.”

Weyand, who has conducted research on the body types of the top 45 100-meter sprinters in the last 15 years, said that almost all elite runners conform to the body norms for their race length, except for the most-recent Olympic champion.

“Bolt is an outlier. He’s enormous,” Weyand said. “Typically when you get someone that big, they can’t start.”

That’s because muscle speed in animals is generally tied to their size. For example, rodents, being much smaller than elephants, can move their muscles much faster. The same holds true for human beings. Sprinters are short and have more fast-twitch muscle fibers, allowing them to accelerate quickly, but compromising their ability to run longer distances. Four hundred-meter runners, almost always taller, have the reverse composition of muscle fibers.

Bolt, though, combines the mechanical advantages of taller men’s bodies with the fast-twitch fibers of smaller men.

“We don’t really know what the best form is and maybe Bolt is redefining that and showing us we missed something,” said biomechanicist John Hutchinson of the Royal Veterinary College at the University of London, who studies how animals move.

Hutchinson also agreed with Weyand that the human speed limit will remain impossible to predict with any confidence.

For him, it’s the International Olympic Committee and other regulatory authorities that will determine how fast athletes will be able to run by limiting the amount of advanced biotechnologies sprinters can use.

“The limits will be largely set by the rules of the IOC,” Hutchinson said. “It’s kind of an arms race with the regulators of the sport and the people trying to push the technology to the limits. At some point here there must be a détente where technology can’t push us any further and the rules will restrict it.”

With techniques for gene therapy likely to become available at some point in the not-too-distant future, Weyand said that its use by athletes was “inevitable.”

“You could see really freakish things and we probably will,” he warned.

Source: Daily Galaxy

Posted in Biology, DNA, Healthy Living, Medical, Men, Science | Tagged: , , | Leave a Comment »

Gray Hair Caused by DNA Damage

Posted by jase on June 19, 2009

Christine Dell’Amore over at National Geographic News posted the following fascinating finding:

Work or personal stress may make you want to pull your hair out, but it’s cellular stress that actually turns it gray, a new study has found.

That’s because DNA is “under constant attack” by damaging agents, such as chemicals, ultraviolet light, and ionizing radiation, according to study lead author Emi Nishimura of Tokyo Medical and Dental University.

A single mammal cell can encounter up to 100,000 events a day that damage DNA, Nishimura added in a statement.

The stem cells within hair follicles responsible for color are the most impacted by this irreparable DNA weathering.

Stem cells are cells in the body that can reproduce indefinitely and that have the potential to “mature” into other, more specialized cells. The stem cells in hair follicles mature into melanocytes, or cells that produce the pigment melanin.

In younger people, the hair’s stem cells maintain a balance between those that reproduce and those that turn into pigment cells, so that pigment is constantly being added to growing hair.

But as a person ages, too many of the stem cells mature until the pool of pigment cells gets totally drained and hair grows gray.

Scientists have been unsure what exactly spurs the stem cells to change. According to Nishimura, the answer may be accumulated DNA damage.

Forcing the cells to mature may be the body’s “more sophisticated way” of purging the damaged stem cells without killing them off, she said.

Unavoidable Damage

The study focused on graying because it is a typical sign of aging in mammals, the authors wrote.

The researchers put laboratory mice through whole-body x-rays and chemical injections.

When the team examined the mice’s hair follicles, they found that the stem cells showed permanent damage. These mice then regrew hair with no pigment.

The research supports the idea that instability in genes may be a major factor in aging, the authors say. It also lends credence to the theory that damage to stem cells may be the main driver of aging.

The DNA damage observed in the study is mainly “unavoidable,” the authors write.

Linzhao Cheng, a member of the Johns Hopkins Institute of Cell Engineering, agreed that it’s tough to avoid stem cell damage—especially for people who spend a lot of time outdoors, which exposes them to ultraviolet radiation from the sun.

However, the study helps scientists understand graying, Cheng said by email, which may lead to new chemicals that can prevent the hair’s stem cells from switching roles.

“We may soon have anti-graying creams for aging populations,” he said.

Posted in Aging, Biology, DNA | Tagged: , , | Leave a Comment »