Thursday, February 14, 2013
The Food and Drug Administration on Thursday approved the first treatment to give limited vision to people who are blind, involving a technology called the "artificial retina."
With it, people with certain types of blindness can detect crosswalks on the street, burners on a stove, the presence of people or cars, and sometimes even oversized numbers or letters.
The artificial retina is a sheet of electrodes surgically implanted in the eye. The patient is also outfitted with a pair of glasses with an attached camera and a portable video processor. These elements together allow visual signals to bypass the damaged portion of the retina and be transmitted to the brain. The F.D.A. approval covers this integrated system, which the manufacturer calls Argus II.
The approval marks the first milestone in a new frontier in vision research, a field in which scientists are making strides with gene therapy, optogenetics, stem cells and other strategies.
"This is just the beginning," said Grace Shen, director of the retinal diseases program at the National Eye Institute, which helped finance the artificial retina research and is supporting many other blindness therapy projects. "We have a lot of exciting things sitting in the wings, multiple approaches being developed now to address this."
With the artificial retina or retinal prosthesis, a blind person cannot see in the conventional sense, but can identify outlines and boundaries of objects, especially when there is contrast between light and dark — fireworks against a night sky or black socks mixed with white ones in the laundry.
"Without the system, I wouldn't be able to see anything at all, and if you were in front of me and you moved left and right, I'm not going to realize any of this," said Elias Konstantopolous, 74, a retired electrician in Baltimore, one of about 50 Americans and Europeans who have been using the device in clinical trials for several years. He said it helps him differentiate curbs from asphalt roads, and detect contours, but not details, of cars, trees and people. "When you don't have nothing, this is something. It's a lot."
The F.D.A. approved Argus II, made by Second Sight Medical Products, to treat people with severe retinitis pigmentosa, a group of inherited diseases in which photoreceptor cells, which take in light, deteriorate.
The first version of the implant had a sheet of 16 electrodes, but the current version has 60. A tiny camera mounted on eyeglasses captures images, and the video processor, worn on a belt, translates those images into pixelized patterns of light and dark. The processor transmits those signals to the electrodes, which send them along the optic nerve to the brain.
About 100,000 Americans have retinitis pigmentosa, but initially between 10,000 and 15,000 will likely qualify for the Argus II, according to the company. The F.D.A. says that up to 4,000 people a year can be treated with the device. That number represents people who are older than 25, who once had useful vision, have evidence of an intact inner retinal layer, have at best very limited light perception in the retina, and are so visually impaired that the device would prove an improvement. Second Sight will begin making Argus II available later this year.
But experts said the technology holds promise for other people who are blind, especially those with advanced age-related macular degeneration, the major cause of vision loss in older people, affecting about two million Americans. About 50,000 of them are currently severely impaired enough that the artificial retina would be helpful, said Dr. Robert Greenberg, Second Sight's president and chief executive.
In Europe, Argus II received approval in 2011 to treat a broader group of people, those with severe blindness caused by any type of outer retinal degeneration, not just retinitis pigmentosa, although it is currently only marketed in Europe for that condition. In the U.S., additional clinical trials need to be completed before the company can seek broader FDA approval.
Eventually, Dr. Greenberg said, the plan is to implant electrodes not in the eye, but directly into the brain's visual cortex. "That would allow us to address blindness from all causes," he said.
Initially, the artificial retina will be available at seven hospitals in five states: New York, California, Texas, Maryland and Pennsylvania. It will cost about $150,000, not including the surgery and training sessions to use the device. Second Sight said it was optimistic that insurance would cover it.
Developed over 20 years by Dr. Mark S. Humayun, an ophthalmologist and biomedical engineer at the University of Southern California's Doheny Retinal Institute, the artificial retina was inspired by cochlear implants for the deaf. Some financing came from a cochlear implant maker and other private sources, but about $100 million was provided by the National Eye Institute, the National Science Foundation and the Department of Energy, all federal agencies.
Dr. Humayun said he envisioned applying the technology to other conditions than blindness, implanting electrodes in other parts of the body to address bladder control problems, perhaps, or spinal paralysis.
"We don't think of the human body as an electrical grid, but it runs off electrical impulses," he said.
The Argus II has had relatively few safety problems, mostly post-surgical infections and occasional erosions of a thin layer in the eye that covered the implant. Those problems have been addressed, Dr. Greenberg said, and only two people needed to have the implant removed. An F.D.A. advisory panel voted unanimously last September to recommend approval, finding that benefits outweighed the risks.
Some patients experience more improvement than others, for reasons the company has not been able to determine. Kathy Blake of Fountain Valley, Calif., said she has had success with a Second Sight exercise to see if patients can identify large numbers or letters on a computer screen.
Dean Lloyd, a lawyer in Palo Alto, Calif., said he initially wondered, "Is it really worth all the time and expense? I, at first, did not think so." Early on, only nine electrodes were working, but over time his implant was adjusted so more electrodes responded, and now 52 of them work. He can see flashes of color, something not every patient can, and he wears the glasses and video processor constantly.
"If I don't wear it, it's like I don't have my pants on," he said. "I've even fallen asleep with the blooming thing."
Stephen Rose, the chief research officer for the Foundation Fighting Blindness, which supported Dr. Humayun's very early work but has not financed it since, said the artificial retina would eventually be only one of the options to help blind people.
"I think there are tremendous possibilities," he said. "I'm not downplaying the retinal prosthesis, don't get me wrong. It's huge for some individuals, and it's here now."
Barbara Campbell, 59, relishes how the device helps her navigate Manhattan streets, locate her Upper East Side bus stop, and spot her apartment building's foyer light while riding in a taxi.
Most exciting, though, is how it enhances her experience of museums, theater and concerts.
At a performance by Rod Stewart, "I could definitely see his hair," she said, which was white-blond under the lights. At a concert by Diana Ross, even though Ms. Campbell sat far away from the stage, she said Ms. Ross "was wearing a sparkly outfit, and I could see her."
No such luck at a performance by James Taylor, though. His low-key clothing created no contrast for the artificial retina to register. Alas, Ms. Campbell said, "He wasn't so sparkly."
Tuesday, February 12, 2013
For decades, mice have been the species of choice in the study of human diseases. But now, researchers report evidence that the mouse model has been totally misleading for at least three major killers — sepsis, burns and trauma. As a result, years and billions of dollars have been wasted following false leads, they say.
The study's findings do not mean that mice are useless models for all human diseases. But, its authors said, they do raise troubling questions about diseases like the ones in the study that involve the immune system, including cancer and heart disease.
"Our article raises at least the possibility that a parallel situation may be present," said Dr. H. Shaw Warren, a sepsis researcher at Massachusetts General Hospital and a lead author of the new study.
The paper, published Monday in Proceedings of the National Academy of Sciences, helps explain why every one of nearly 150 drugs tested at a huge expense in patients with sepsis has failed. The drug tests all were based on studies in mice. And mice, it turns out, can have something that looks like sepsis in humans, but is very different from the condition in humans.
Medical experts not associated with the study said that the findings should change the course of research worldwide for a deadly and frustrating condition. Sepsis, a potentially deadly reaction that occurs as the body tries to fight an infection, afflicts 750,000 patients a year in the United States, kills one-fourth to one-half of them, and costs the nation $17 billion a year. It is the leading cause of death in intensive-care units.
"This is a game changer," said Dr. Mitchell Fink, a sepsis expert at the University of California, Los Angeles, of the new study.
"It's amazing," said Dr. Richard Wenzel, a former chairman at the department of internal medicine at Virginia Commonwealth University and a former editor of The New England Journal of Medicine. "They are absolutely right on."
Potentially deadly immune responses occur when a person's immune system overreacts to what it perceives as danger signals, including toxic molecules from bacteria, viruses, fungi, or proteins released from cells damaged by trauma or burns, said Dr. Clifford S. Deutschman, who directs sepsis research at the University of Pennsylvania and was not part of the study.
The ramped-up immune system releases its own proteins in such overwhelming amounts that capillaries begin to leak. The leak becomes excessive, and serum seeps out of the tiny blood vessels.Blood pressure falls, and vital organs do not get enough blood. Despite efforts, doctors and nurses in an intensive-care unit or an emergency room may be unable to keep up with the leaks, stop the infection or halt the tissue damage. Vital organs eventually fail.
The new study, which took 10 years and involved 39 researchers from across the country, began by studying white blood cells from hundreds of patients with severe burns, trauma or sepsis to see what genes were being used by white blood cells when responding to these danger signals.
The researchers found some interesting patterns and accumulated a large, rigorously collected data set that should help move the field forward, said Ronald W. Davis, a genomics expert at Stanford University and a lead author of the new paper. Some patterns seemed to predict who would survive and who would end up in intensive care, clinging to life and, often, dying.
The group had tried to publish its findings in several papers. One objection, Dr. Davis said, was that the researchers had not shown the same gene response had happened in mice.
"They were so used to doing mouse studies that they thought that was how you validate things," he said. "They are so ingrained in trying to cure mice that they forget we are trying to cure humans."
"That started us thinking," he continued. "Is it the same in the mouse or not?"
The group decided to look, expecting to find some similarities. But when the data were analyzed, there were none at all.
"We were kind of blown away," Dr. Davis said.
The drug failures became clear. For example, often in mice, a gene would be used, while in humans, the comparable gene would be suppressed. A drug that worked in mice by disabling that gene could make the response even more deadly in humans.
Even more surprising, Dr. Warren said, was that different conditions in mice — burns, trauma, sepsis — did not fit the same pattern. Each condition used different groups of genes. In humans, though, similar genes were used in all three conditions. That means, Dr. Warren said, that if researchers can find a drug that works for one of those conditions in people, it might work for all three.
The study's investigators tried for more than a year to publish their paper, which showed that there was no relationship between the genetic responses of mice and those of humans. They submitted it to the publications Science and Nature, hoping to reach a wide audience. It was rejected from both.
Science and Nature said it was their policy not to comment on the fate of a rejected paper, or whether it had even been submitted to them. But, Ginger Pinholster of Science said, the journal accepts only about 7 percent of the nearly 13,000 papers submitted each year, so it is not uncommon for a paper to make the rounds.
Still, Dr. Davis said, reviewers did not point out scientific errors. Instead, he said, "the most common response was, 'It has to be wrong. I don't know why it is wrong, but it has to be wrong.' "
The investigators turned to Proceedings of the National Academy of Sciences. As a member of the academy, Dr. Davis could suggest reviewers for his paper, and he proposed researchers who he thought would give the work a fair hearing. "If they don't like it, I want to know why," he said. They recommended publication, and the editorial board of the journal, which independently assesses papers, agreed.
Some researchers, reading the paper now, say they are as astonished as the researchers were when they saw the data.
"When I read the paper, I was stunned by just how bad the mouse data are," Dr. Fink said. "It's really amazing — no correlation at all. These data are so persuasive and so robust that I think funding agencies are going to take note." Until now, he said, "to get funding, you had to propose experiments using the mouse model."
Yet there was always one major clue that mice might not really mimic humans in this regard: it is very hard to kill a mouse with a bacterial infection. Mice need a million times more bacteria in their blood than what would kill a person.
"Mice can eat garbage and food that is lying around and is rotten," Dr. Davis said. "Humans can't do that. We are too sensitive."
Researchers said that if they could figure out why mice were so resistant, they might be able to use that discovery to find something to make people resistant.
"This is a very important paper," said Dr. Richard Hotchkiss, a sepsis researcher at Washington University who was not involved in the study. "It argues strongly — go to the patients. Get their cells. Get their tissues whenever you can. Get cells from airways."
"To understand sepsis, you have to go to the patients," he said.
Sunday, February 10, 2013
Quick links from the past week in mind and brain news:
The New York Times covers the recent upsurge of robots-taking-over-the-world anxiety. To the bunkers!
The dodgy practice of psychologists trying to patenttherapeutic techniques is covered by Neuroskeptic.
The Humanist discusses the explosion of the unhelpful concept of sex addition.
Forensic psychology nerds: In The News covers the latest in the debate on theaccuracy of violence risk assessments.
The Bangkok Post on the bizarre Thai government announcement that calculators, phones "and even karaoke machines" could damage memory, lead to Alzheimer's disease. Bryan Adams covers, screaming fits. 80s hair metal, unfortunately lycra incidents.
People without an amygdala can experience fear. Neurophilosophy covers an intriguing new study.
Wired Danger Room on the cost of war to the US: currently, at least 253,330 brain injuries, 129,731 cases of PTSD – and counting.
Missouri Public Radio on how ex- Abu Ghraib chief psychologist Larry James wants to launch a national gun violence prevention center. Presumably, by waterboarding assault rifle owners.
Short-term exercise boosts body image without making any physical difference. The BPS Research Digest on the short-term psychological effects of exercise.
Scientific American has an important piece on the science of what life events can trigger depression.