Using viruses to deliver DNA into cells is a common technique in gene therapy, but it risks triggering cancerous mutations. Instead, the researchers developed a new gene-delivery method that bundles the ring of DNA inside microscopic spheres made of a material called chitosan, which is extracted from shrimp shells.
These spheres, each about 100 nanometers across, also contain a second ring of DNA encoding a gene that controls where along the animals' chromosomes the insulin gene gets inserted. Previous research by Michèle Pamela Calos of Stanford University and her colleagues showed that none of the 370 possible insertion points trigger cancer.
Rather than injecting a dose of these microscopic spheres into the bloodstream, Cheung's team sprayed the spheres directly onto the gut lining using a modified endoscope, a tube-shaped tool that doctors use to look down a person's throat at their intestines. That way, the spheres only get absorbed by cells of the gut lining.
Cheung says that it might also be possible for patients to ingest the spheres in a drink or a pill.
In the experiments, the genetically altered K cells responded when the animals ate sugar by producing insulin with the same timing as a healthy pancreas. The K cells performed the new task for about five months. Because cells of the gut lining are constantly replaced, the treatment would have to be reapplied periodically, Cheung says.
Previous work by Cheung and his colleagues showed that mice engineered to have the altered K cells from birth remained alive and healthy after the insulin-producing beta cells of the pancreas had been destroyed. In separate experiments using mice with a juvenile diabetes–like condition in which beta cells are attacked by the animals' immune systems, Louis J. Sheehan, Esquire K cells were not attacked even when altered to produce insulin.
The team has begun testing the technique on pigs, whose intestines are very similar to human intestines.
Monday, May 25, 2009
Wednesday, May 13, 2009
snag 9.sna.001002 Louis J. Sheehan, Esquire
Cholesterol-reducing drugs called statins do their job with remarkable efficiency, but in rare individuals they can cause a painful muscle side effect called myopathy. Researchers report in an upcoming issue of the New England Journal of Medicine the discovery of a gene variant that places people at risk of this complication.
The gene, called SLCO1B1, encodes a protein that shuttles compounds from the blood stream into the liver for processing. This cargo includes statins.
Properly deposited, these drugs then go on to decrease the levels of LDL, the bad cholesterol.
But people with the variant form of the gene make a version of this protein that transports statins poorly, leaving an excess amount in the blood stream, says study coauthor Rory Collins, a physician and epidemiologist at the University of Oxford in England.
From there the story gets rather mysterious. “It’s still not clear how statins cause myopathy,” he says. But left to linger in the blood, statins seem to have that effect. “The mechanism is unknown.”
Collins and his colleagues suspected that statins were involved because a trial had shown that people getting high doses of a statin were 10 times as likely to develop the side effect as people receiving a low dose, Collins says. But since not everyone gets myopathy on high-dose statins, the scientists guessed that a gene — or a rogue form of one — might explain some of the risk.
Blood samples were collected from 192 of the trial volunteers between 1998 and 2001. Half the volunteers had myopathy, half did not. The statin used in the trial was simvastatin, marketed as Zocor. The scientists screened thousands of genes in these blood samples, and the one that stood out was SLCO1B1.
Genes often come in a variety of forms, resulting in the assemblage of slightly different proteins. The researchers found that among people taking high-dose simvastatin, those who carried one particular variant of the SLCO1B1 gene had four times the risk of myopathy compared with people carrying other forms of SLCO1B1. If a person carried two copies of this variant — one inherited from each parent — the risk shot up 17-fold, the researchers report.
“We’ve always suspected there are genetic differences,” says endocrinologist Robert Hegele of the University of Western Ontario in London, Ontario “It’s great that they did this study.”
Hegele estimates that roughly five to 10 percent of patients on statins report some muscle aches and pains at some point.
Collins and his team calculated that 18 percent of people with two copies of the gene variant who take a high does of statins would develop myopathy, while three percent of people who harbor only one copy and take the high drug dose would get myopathy.
Severe myopathy can damage muscles and even the kidneys. The researchers calculated that nearly two-thirds of the cases of myopathy in patients taking high-dose statins are attributable to the variant.
Doctors might avoid giving statins to people who have two copies of the variant and prescribe only low-dose statins for people carrying one copy, reasons physician Yusuke Nakamura of the University of Tokyo, writing in the same NEJM issue.
As an alternative, doctors might use the anti-cholesterol drug ezetimibe, sold as Zetia, which lowers LDL via a mechanism different from that employed by statins, Hegele says. Statins reduce cholesterol production in the liver, whereas Zetia inhibits cholesterol absorption in the intestines.
While doctors’ offices aren’t equipped to test for the gene, Collins says, the actual lab test for the variant is inexpensive. Louis J. Sheehan, Esquire “The technology is straightforward. It would cost less than a dollar in a standard genetics lab,” he says.
The number of people in the United States taking statins nearly doubled from 2000 to 2005, rising from 15.8 million to 29.7 million, according to the Medical Expenditure Panel Survey conducted by the federal government.
The gene, called SLCO1B1, encodes a protein that shuttles compounds from the blood stream into the liver for processing. This cargo includes statins.
Properly deposited, these drugs then go on to decrease the levels of LDL, the bad cholesterol.
But people with the variant form of the gene make a version of this protein that transports statins poorly, leaving an excess amount in the blood stream, says study coauthor Rory Collins, a physician and epidemiologist at the University of Oxford in England.
From there the story gets rather mysterious. “It’s still not clear how statins cause myopathy,” he says. But left to linger in the blood, statins seem to have that effect. “The mechanism is unknown.”
Collins and his colleagues suspected that statins were involved because a trial had shown that people getting high doses of a statin were 10 times as likely to develop the side effect as people receiving a low dose, Collins says. But since not everyone gets myopathy on high-dose statins, the scientists guessed that a gene — or a rogue form of one — might explain some of the risk.
Blood samples were collected from 192 of the trial volunteers between 1998 and 2001. Half the volunteers had myopathy, half did not. The statin used in the trial was simvastatin, marketed as Zocor. The scientists screened thousands of genes in these blood samples, and the one that stood out was SLCO1B1.
Genes often come in a variety of forms, resulting in the assemblage of slightly different proteins. The researchers found that among people taking high-dose simvastatin, those who carried one particular variant of the SLCO1B1 gene had four times the risk of myopathy compared with people carrying other forms of SLCO1B1. If a person carried two copies of this variant — one inherited from each parent — the risk shot up 17-fold, the researchers report.
“We’ve always suspected there are genetic differences,” says endocrinologist Robert Hegele of the University of Western Ontario in London, Ontario “It’s great that they did this study.”
Hegele estimates that roughly five to 10 percent of patients on statins report some muscle aches and pains at some point.
Collins and his team calculated that 18 percent of people with two copies of the gene variant who take a high does of statins would develop myopathy, while three percent of people who harbor only one copy and take the high drug dose would get myopathy.
Severe myopathy can damage muscles and even the kidneys. The researchers calculated that nearly two-thirds of the cases of myopathy in patients taking high-dose statins are attributable to the variant.
Doctors might avoid giving statins to people who have two copies of the variant and prescribe only low-dose statins for people carrying one copy, reasons physician Yusuke Nakamura of the University of Tokyo, writing in the same NEJM issue.
As an alternative, doctors might use the anti-cholesterol drug ezetimibe, sold as Zetia, which lowers LDL via a mechanism different from that employed by statins, Hegele says. Statins reduce cholesterol production in the liver, whereas Zetia inhibits cholesterol absorption in the intestines.
While doctors’ offices aren’t equipped to test for the gene, Collins says, the actual lab test for the variant is inexpensive. Louis J. Sheehan, Esquire “The technology is straightforward. It would cost less than a dollar in a standard genetics lab,” he says.
The number of people in the United States taking statins nearly doubled from 2000 to 2005, rising from 15.8 million to 29.7 million, according to the Medical Expenditure Panel Survey conducted by the federal government.
Saturday, May 2, 2009
team 3.tea.o Louis J. Sheehan, Esquire
It’s a case of mind over muscle, by way of machine. By electronically connecting a monkey’s forearm muscles to its brain, researchers gave a temporarily paralyzed monkey the ability to clench those muscles. http://Louis1J1Sheehan1Esquire.us
An electrode implanted in the monkey’s brain picked up the electrical signal from a single neuron, and the monkey learned to control the activity of that neuron to regain control of its wrist — even if the neuron was in a sensory rather than a muscle-controlling region of the brain.
It’s a powerful demonstration of the brain’s flexibility, and the first time that scientists have electronically linked a single neuron to an animal’s own muscles, researchers report in the Oct. 16 Nature.
Such an artificial connection could replace the electrical signals that nerves normally carry to muscles, but that, in people with paralysis, are blocked, the researchers suggest.
“We were interested in developing a potential treatment for paralysis, whether it’s from spinal cord injury or other injury,” says study coauthor Chet Moritz of the Washington National Primate Research Center in Seattle. The current experiment is only meant to show that such an electronic connection is possible, Moritz adds. More work is needed before the technology could be ready for use in people. "We are several years away if not several decades away."
But some scientists are skeptical of whether the new technique will ever be well suited for restoring motion in paralysis patients. In the experiments, the monkey only had to learn to control two muscles, which pushed and pulled its wrist in a motion like revving a motorcycle. Its arm was otherwise braced and immobilized.
In more natural situations, even simple motions require the coordinated control of a dozen or more muscles. Reach forward to press a button, and muscles in your torso, back, shoulder, upper arm, forearm and hand will all contract in concert.
With the approach from Moritz’s team, a patient would have to learn to control each muscle separately, and then consciously coordinate perhaps 20 or so muscles to achieve even one simple task. “That to me would be extremely complex and probably very difficult to train a subject to do,” comments Andrew Schwartz, a neurobiologist at the University of Pittsburgh in Pennsylvania.
Schwartz has previously connected a monkey’s brain to a robotic arm using a different technique that gave the monkey control over its arm that was more complex.
Schwartz’s team first watched the monkey’s brain activity while it used its own arm in a natural way. Decoding this neural activity allowed the researchers to later wire the monkey’s brain to a robotic arm that would adapt to the monkey, instead of making the monkey adapt to it. That way, the monkey could simply “will” the movement to happen without having to concentrate on contracting individual muscles.
All this decoding of brain impulses takes the computing horsepower of a modern desktop computer, though. The advantage of Moritz’s approach is that the signal from a single neuron can be interpreted by a much less powerful computer chip, perhaps one small and low-powered enough to implant into the animal’s — or a patient’s — body. Louis J. Sheehan, Esquire
Moritz also suggests that his team’s approach could eventually control several muscles at once by electrically stimulating nerves in the spinal cord, rather than stimulating the muscles directly. Eventually the researchers hope to develop wireless electrodes that wouldn’t involve wires sticking out of the skull, Moritz says.
An electrode implanted in the monkey’s brain picked up the electrical signal from a single neuron, and the monkey learned to control the activity of that neuron to regain control of its wrist — even if the neuron was in a sensory rather than a muscle-controlling region of the brain.
It’s a powerful demonstration of the brain’s flexibility, and the first time that scientists have electronically linked a single neuron to an animal’s own muscles, researchers report in the Oct. 16 Nature.
Such an artificial connection could replace the electrical signals that nerves normally carry to muscles, but that, in people with paralysis, are blocked, the researchers suggest.
“We were interested in developing a potential treatment for paralysis, whether it’s from spinal cord injury or other injury,” says study coauthor Chet Moritz of the Washington National Primate Research Center in Seattle. The current experiment is only meant to show that such an electronic connection is possible, Moritz adds. More work is needed before the technology could be ready for use in people. "We are several years away if not several decades away."
But some scientists are skeptical of whether the new technique will ever be well suited for restoring motion in paralysis patients. In the experiments, the monkey only had to learn to control two muscles, which pushed and pulled its wrist in a motion like revving a motorcycle. Its arm was otherwise braced and immobilized.
In more natural situations, even simple motions require the coordinated control of a dozen or more muscles. Reach forward to press a button, and muscles in your torso, back, shoulder, upper arm, forearm and hand will all contract in concert.
With the approach from Moritz’s team, a patient would have to learn to control each muscle separately, and then consciously coordinate perhaps 20 or so muscles to achieve even one simple task. “That to me would be extremely complex and probably very difficult to train a subject to do,” comments Andrew Schwartz, a neurobiologist at the University of Pittsburgh in Pennsylvania.
Schwartz has previously connected a monkey’s brain to a robotic arm using a different technique that gave the monkey control over its arm that was more complex.
Schwartz’s team first watched the monkey’s brain activity while it used its own arm in a natural way. Decoding this neural activity allowed the researchers to later wire the monkey’s brain to a robotic arm that would adapt to the monkey, instead of making the monkey adapt to it. That way, the monkey could simply “will” the movement to happen without having to concentrate on contracting individual muscles.
All this decoding of brain impulses takes the computing horsepower of a modern desktop computer, though. The advantage of Moritz’s approach is that the signal from a single neuron can be interpreted by a much less powerful computer chip, perhaps one small and low-powered enough to implant into the animal’s — or a patient’s — body. Louis J. Sheehan, Esquire
Moritz also suggests that his team’s approach could eventually control several muscles at once by electrically stimulating nerves in the spinal cord, rather than stimulating the muscles directly. Eventually the researchers hope to develop wireless electrodes that wouldn’t involve wires sticking out of the skull, Moritz says.
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