Science Weekly Live: What makes a genius?

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Recorded live at London’s Science Museum, Alok Jha and the panel explore what it means to be a genius

Stimulating the vagus nerve may help block phantom sounds by reorganizing the brain

MIT Technology Review, May 27, 2010, by Emily Singer  –  Electrically stimulating the vagus nerve, which connects the brain and the visceral organs, could help temper the phantom sounds that plague tinnitus sufferers. Researchers from Microtransponder, a Dallas-based startup developing wireless stimulation technology, reported at a neurotechnology conference in Boston this week that the approach works in animals with auditory damage that mimics the disorder. The company is adapting its neurostimulation technology, currently being developed for chronic pain, to target the vagus nerve.

Tinnitus, the false perception of ringing or other sounds in the ear, affects millions of people worldwide. Most often associated with hearing loss, it has become an especially common problem in soldiers exposed to loud blasts. The severity of the disorder varies widely, from relatively benign to debilitating, and the few existing treatments tend to mask the intrusive sound rather than eliminate it.

While it’s unclear exactly what causes tinnitus, research suggests it arises from the brain’s attempt to compensate for hearing loss. Damage to the inner ear, which translates sound vibrations into neural signals for the brain, results in less input to the brain’s auditory pathways. The brain appears to try to make up for this loss of input by increasing activity, which may in turn result in phantom sounds.

Michael Kilgard, a neuroscientist at the University of Texas, aims to reverse this maladaptive reorganization using a combination of electrical stimulation and sound. Kilgard has previously shown that stimulating part of the brain called the nucleus basalis while playing a particular tone triggers the auditory cortex to reorganize to become hyper-responsive to that tone. To treat tinnitus, the idea is to stimulate this area while playing all sound frequencies except the one corresponding to a patient’s phantom sound, thus signaling to the brain to become more responsive to all these other frequencies. If successful, this would rebalance the auditory cortex.

Rather than targeting the brain directly in humans, Kilgard turned to the vagus nerve, part of the nervous system that connects the stomach, liver, and other organs to the brain. Implanted devices that stimulate the vagus nerve are currently approved to treat depression and epilepsy and are being tested for other disorders.

Researchers plan to test the concept in people with tinnitus in upcoming clinical trials in Belgium. Kilgard says the researchers will use simple electrodes, which are implanted at the neck and stimulated with an external device. While the exact parameters are still to be determined, patients will undergo treatment for half an hour to an hour each day, for days or weeks. Unlike vagus nerve stimulation for epilepsy, which involves chronic stimulation, treatment for tinnitus will likely be for a limited period of time, researchers say.

In conjunction with these clinical tests, Microtransponder is modifying its existing technology for tinnitus. Unlike other stimulation devices, Microtransponder’s system is wireless and has no batteries. The implanted portion consists of small electrodes and a small coil. An external battery-powered coil worn like a cuff on the arm or leg powers the device. “The idea would be to inject the wireless device and then put a coil around the neck to activate it [during a treatment session],” says Kilgard. “If the tinnitus comes back five years later, the device is still there and you can do the treatment again.

Harvard’s Melcher says the approach is very interesting, though “whether it works is an open question.” She points out that “we are still trying to sort out what aspects of brain plasticity are involved in tinnitus. There may be different kinds of tinnitus, with different types of brain activity giving rise to the perception of sounds that aren’t there.” All of these may require different treatments.

Tinnitus is the name given to the condition of noises ‘in the ears’ and/or ‘in the head’ with no external source. Tinnitus noises are described variously as ringing, whistling, buzzing and humming.

The noise/s may be heard in one ear, both ears or in the middle of the head or it may be difficult to pinpoint its exact location. The noise may be low, medium or high-pitched. There may be a single noise or two or more components. The noise may be continuous or it may come and go.

What causes tinnitus?

Tinnitus is not a disease or an illness, it is a symptom generated within a person’s own auditory pathways. Although it is often assumed that tinnitus occurs as a result of disease of the ears, this is often not the cause. The precise cause of tinnitus is still not fully understood but is usually associated with some hearing deficits. Damage caused to the hearing nerve in the inner ear is one of the most commons causes of tinnitus. Listening to loud noises such as music from an ipod, heavy machinery, and firearms can also cause tinnitus. There is no way to cure tinnitus and age can be another factor that plays a role in the onset of tinnitus symptoms.

Who gets tinnitus?

Experiences of tinnitus are very common in all age groups, especially following exposure to loud noise, however, it is unusual for it to be a major problem. There is a widely held misconception that tinnitus is confined to the elderly, but various studies have shown that it can occur at any age, even quite young children. Mild tinnitus is common – about 10 per cent of the population have it all the time and, in up to one per cent of adults, this may affect the quality of their life.

Who’s at Risk?

 

Many professions and activites can put you at risk for getting tinnitus. People around loud industial noise, such machinists, airport workers, military personnel & carpenters are all at risk. Activities such as listening to loud music, whether on an mp3 player, at a concert, or in a nightclub can also put you in the at-risk category.

GoogleNews.com  —  Acupuncture and trigger point therapy may be effective treatments for people suffering from tinnitus — a ringing in the ears — a U.S. study found.

Susan Shore of the University of Michigan’s Kresge Hearing Research Institute said nerves that “sense touch” in the face and neck may be behind the ringing that people with tinnitus hear.

The study, published online in the European Journal of Neuroscience, said touch-sensing nerve cells step up their activity in the brain after hearing cells are damaged, and hyperactivity of these touch-sensing neurons likely plays an important role in tinnitus.

The research findings were made in studies involving animals, but the research suggests treatments such as acupuncture — if used to target nerves in the head and neck — may provide relief for some people plagued by tinnitus.

University of Alabama professor Craig Formby looks on as Adam Jones spins in a Roto-Tilt Chair in a demonstration in the AIME Building on the University of Alabama campus.

GoogleNews.com, by Adam Jones  –  A University of Alabama researcher is leading a $3.2 million clinical study of a treatment of severe tinnitus, or ringing in the ear.

Tinnitus?

What it is: Ringing in the ears. About 50 million Americans say they have experienced it, but fewer than 5 million say it is debilitating.
What causes it: Causes aren’t fully known, but in some cases loud noises, such as gunfire, can trigger it.
How to treat it: There is no known cure, since tinnitus isn’t fully understood. Formby’s trial will combine counseling with a hearing aid-like device that makes a sound in the patient’s ear that will blend in with the ringing. With prolonged use, patients may begin to become less affected by tinnitus.

“There’s been a lot of attempts to come up with treatments, but nothing has been very successful,” said Craig Formby, a UA graduate research professor in audiology.

About 50 million Americans say they suffer from tinnitus, but a smaller group, less than 5 million, say the ringing is debilitating. For those people, tinnitus is an all-consuming disease that dominates their life, Formby said.

“We’re trying to bring people back into the pack of those who aren’t bothered by it,” he said.

The treatment being tested is non-medical and is hoped to help patients live with the disease. There is no known cure for the ringing, since the disease is not fully understood.

The new method, called tinnitus retraining therapy, will combine current methods of counseling with a hearing aid like device that will pipe a sound into the ear that blends with the ringing, Formby said.

Patients are encouraged to use the device all day in an effort to help them cope with the ringing. They are asked to try to live a normal day and forget the devices are in, he said.

Previous work has shown about 80 percent of people who undergo the treatment and use the device consistently report diminished influence of tinnitus, Formby said.

Formby didn’t invent the treatment, but he and his UA team will lead the trial, paid for by a $3.2 million award from the National Institute of Deafness and Other Communication Disorders. If successful, the treatment will likely be accepted as standard.

“It’s not new or innovative, it just needs to be tested out,” Formby said. “Ours is sort of be-all, end-all of whether this works and is a viable treatment for people to consider.”

Researchers at Johns Hopkins University have a $2.4 million award to manage and analyze the study data. The project will be spread over five years, including four years for recruiting study participants and conducting the treatment and follow-up measurements, according to a UA news release.

All the patients will be drawn from U.S. Navy and Air Force hospitals in California, Texas, Maryland and Virginia. Researchers expect to recruit 228 participants for the study.

Tinnitus is the military’s Number 1 disability among veterans returning from the Middle East conflicts. In 2008, compensation for tinnitus disability in the Veteran Affairs medical system was more than $500 million and is projected to exceed $1.1 billion and affect more that 800,000 veterans by 2011, according to a UA news release.

It’s not clear what causes tinnitus, but loud noises, such as gunfire, can trigger it in some cases, Formby said.

For more info, Reach Adam Jones at 205-722-0230

They Fly 7,000+ Miles, 40 MPH, Nonstop in 9 Days –

Awesome Lesson in Tenacity and Focus

The Amazing Bar-tailed Godwit

The New York Times, May 27, 2010, by Carl Zimmer  –  In 1976, the biologist Robert E. Gill Jr. came to the southern coast of Alaska to survey the birds preparing for their migrations for the winter. One species in particular, wading birds called bar-tailed godwits, puzzled him deeply. They were too fat.

“They looked like flying softballs,” said Mr. Gill.

At the time, scientists knew that bar-tailed godwits spend their winters in places like New Zealand and Australia. To get there, most researchers assumed, the birds took a series of flights down through Asia, stopping along the way to rest and eat. After all, they were land birds, not sea birds that could dive for food in the ocean. But in Alaska, Mr. Gill observed, the bar-tailed godwits were feasting on clams and worms as if they were not going to be able to eat for a very long time.

“I wondered, why is that bird putting on that much fat?” he said.

Mr. Gill wondered if the bar-tailed godwit actually stayed in the air for a much longer time than scientists believed. It was a difficult idea to test, because he could not actually follow the birds in flight. For 30 years he managed as best he could, building a network of bird-watchers who looked for migrating godwits over the Pacific Ocean. Finally, in 2006, technology caught up with Mr. Gill’s ideas. He and his colleagues were able to implant satellite transmitters in bar-tailed godwits and track their flight.

The transmitters sent their location to Mr. Gill’s computer, and he sometimes stayed up until 2 in the morning to see the latest signal appear on the Google Earth program running on his laptop. Just as he had suspected, the bar-tailed godwits headed out over the open ocean and flew south through the Pacific. They did not stop at islands along the way. Instead, they traveled up to 7,100 miles in nine days — the longest nonstop flight ever recorded. “I was speechless,” Mr. Gill said.

Since then, scientists have tracked a number of other migrating birds, and they are beginning now to publish their results. Those results make clear that the bar-tailed godwit is not alone. Other species of birds can fly several thousand miles nonstop on their migrations, and scientists anticipate that as they gather more data in the years to come, more birds will join these elite ranks.

“I think it’s going to be a number of examples,” said Anders Hedenström of Lund University in Sweden.

As more birds prove to be ultramarathoners, biologists are turning their attention to how they manage such spectacular feats of endurance. Consider what might be the ultimate test of human endurance in sports, the Tour de France: Every day, bicyclists pedal up and down mountains for hours. In the process, they raise their metabolism to about five times their resting rate.

The bar-tailed godwit, by contrast, elevates its metabolic rate between 8 and 10 times. And instead of ending each day with a big dinner and a good night’s rest, the birds fly through the night, slowly starving themselves as they travel 40 miles an hour.

“I’m in awe of the fact that birds like godwits can fly like this,” said Theunis Piersma, a biologist at the University of Groningen.

Not long ago, ornithologists had far lower expectations for birds. Ruby-throated hummingbirds, for example, were known to spend winters in Central America and head to the United States for the summer. But ornithologists believed that the hummingbirds burned so much fuel flapping their wings that they simply could not survive a nonstop trip across the Gulf of Mexico. They were thought to have flown over Mexico, making stops to refuel.

In fact, ruby-throated hummingbirds returning north in the spring will set out from the Yucatán Peninsula in the evening and arrive in the southern United States the next afternoon.

In the 1960s, zoologists began to track bears and other mammals with radio collars, and then later moved on to satellite transmitters. All the while, ornithologists could only look on in envy. The weight and drag of the trackers made them impossible to put on migrating birds.

Over the past decade, however, transmitters have finally shrunk to a size birds can handle. In Mr. Gill’s first successful experiment with bar-tailed godwits, he and his colleagues slipped a battery-powered model weighing just under an ounce into the abdominal cavity of the birds, which weigh about 12 ounces and have a wingspan of 30 inches.

The epic odyssey that those transmitters recorded spurred Mr. Gill and other researchers to gather more data, both on bar-tailed godwits and other species. And even as they planned their experiments, tracking technology got better. This summer, for example, Mr. Gill will implant bar-tailed godwits with transmitters that weigh only six-tenths of an ounce.

Still, most migrating birds are so small that even a transmitter of that weight — about the same as three nickels — would be an intolerable burden. Fortunately, researchers have been able to scale down a different kind of tracking device. Known as a geolocator, it can get as light as two grains of rice, less than two-hundreths of an ounce. “Now we can track really small birds,” Dr. Hedenström said.

Geolocators can get so small because they do not communicate with satellites. Instead, they just record changing light levels. If scientists can recapture birds carrying geolocators, they can retrieve the data from the devices and use sophisticated computer programs to figure out the location of the birds based on the rising and setting of the sun.

In 2007, Carsten Egevang of Aarhus University in Denmark and his colleagues attached geolocators to Arctic terns nesting in Greenland. Based on years of bird spotting, the scientists knew that the terns migrated to the Southern Ocean around Antarctica and then returned to the Arctic the following spring. But they did not know much more than that. “It was all based on snapshots,” Dr. Egevang said.

In 2008, the scientists managed to capture 10 Arctic terns that had come back to Greenland. It then took them months to make sense of the data. “You have to use three kinds of special software,” Dr. Egevang said. “It takes quite a long time.”

The researchers reported this February that the Arctic terns flew from Greenland to a region of the Atlantic off the coast of North Africa, where they spent about three weeks. Unlike bar-tailed godwits, which wade on beaches for food, Arctic terns are ocean birds that can dive for fish in the open sea.

The Arctic terns then resumed their journey south. They spent five months in the Southern Ocean. “They probably just stayed on an iceberg and fished,” Dr. Egevang said.

In the spring, the terns then returned to the Arctic, often hugging the coasts of South America or Africa along the way. All told, the birds logged as much as 49,700 miles on their geolocators, the longest migration ever recorded. Over the 30-year lifetime of a tern, it may migrate about 1.5 million miles — the distance a spaceship would cover if it went to the moon and back three times.

Other scientists are now placing geolocators on small wading birds as well. In a paper to be published in the Wader Study Group Bulletin, a team of ornithologists describe attaching geolocators to four ruddy turnstones. The birds left northern Australia in May 2009 and flew nonstop to Taiwan, a distance of 4,700 miles.

After a few days in Taiwan, the ruddy turnstones took flight again, making a series of trips northward until they reached Alaska. At the end of the summer, three of the four birds took the same route back south. The fourth struck out on a different path. It flew 3,800 miles nonstop to the Gilbert Islands in the Pacific. From there, it flew 3,100 miles back to Australia.

Mr. Gill and his colleagues have recorded similar odysseys from other wading birds, using satellite transmitters. They found that bristle-thighed curlews fly as far as 6,000 miles without a stop, traveling from Alaska to the Marshall Islands. They have also recorded whimbrels flying 5,000 miles nonstop from Alaska to Central America.

This spring, scientists are attaching geolocators to more birds, and they expect to find new champions. One population of red knots, for example, is now arriving in Delaware Bay from its wintering grounds 5,500 miles away in Argentina. “My bet is that a lot of them make it in one go,” Dr. Piersma said.

The long journeys these transmitters are revealing pose a biological puzzle. Dr. Piersma and other scientists are trying to figure out how the birds manage to push their bodies so far beyond most animals, and why.

As Mr. Gill observed when he first observed bar-tailed godwits, a long journey requires a lot of food. It turns out that long-distance migrators will enlarge their liver and intestines as they feed, so that they can convert their food as fast as possible. They build up large breast muscles and convert the rest of their food to fat.

By the time the birds are ready to leave, their bodies are 55 percent fat. In humans, anything more than 30 percent is considered obese. But as soon as the birds are done eating, their livers and intestines become dead weight. They then essentially “eat” their organs, which shrink 25 percent. The birds use the proteins to build up their muscles even more.

Once they take flight, the birds take whatever help they can get. Bar-tailed godwits time their departure with the onset of stormy weather, so that they can take advantage of tailwinds. “That gives them an extra push,” Dr. Hedenström said.

The birds then fly for thousands of miles. How they get to their final destinations remains a mystery. One thing is clear: they somehow know where they are, even when they are flying over vast expanses of featureless ocean. “It’s as if they have a GPS on board,” Dr. Piersma said.

A bird like a bar-tailed godwit cannot rely on the tricks used by birds that take short migrations. They cannot follow landmarks, for example. Some birds use the Earth’s magnetic field to navigate. But they do so by sensing the tilt of the field lines. At the equator, the lines run parallel to the surface, making them useless for birds that have to travel between hemispheres. Dr. Piersma suspects that when birds travel several thousand miles, they have to combine several different navigation tricks together.

As spectacular as these migrations may be, it may not take long for birds to evolve them. Long-distance migrators are closely related to short-distance birds. It is possible that many birds have the potential to push themselves to make these vast journeys, but they do not because the costs outweigh the benefits.

When animals raise their metabolism above four or five times their resting rate (the Tour de France level), they can become so exhausted that they become very vulnerable to predators. They can even become more prone to getting sick. Birds that go on long migrations may have escaped this tradeoff.

Birds like the bar-tailed godwit have found places like the coast of Alaska where the supply of food is high and predators are scarce. By flying over the open ocean, they continue to avoid predators. They may also reduce their odds of picking up a parasite from another bird.

Their destinations are also safe enough for them to recover. Bar-tailed godwits that arrive in New Zealand face no predators, and so they can simply rest. “They just look exhausted. They’ll land and just go to sleep for several hours before they do anything else,” Mr. Gill said.

Unfortunately, some of the habitats on which these endurance champions depend are under serious threat. In the Delaware Bay, for example, fisherman are scooping up horseshoe crab eggs, which birds like the red knot travel thousands of miles to eat. When bar-tailed godwits return to Alaska in the spring, they make one stop along the coast of China and Korea, a favorite spot for many other migrating birds. The coastal wetlands there are disappearing fast, and many migrant birds are in decline.

“I hope we have these birds to study 100 years from now,” Dr. Piersma said. “But sometimes I wonder.”

Robert E. Gill Jr.
TRACKERS On Alaska’s Yukon River delta, scientists implant a transmitter in a bristle-thighed curlew. The birds fly as far as 6,000 miles without a stop.

Carsten Egevang

FOR THE RECORD Researchers attached geolocators weighing as little as two grains of rice to Arctic terns like this one.

Photo Credit: cjnew

Eye colors: Drusen, the yellow flecks in this image of the retina, are common in people with age-related macular degeneration. These flecks are made up of proteins involved in the part of the immune system called the complement system, which has also been implicated in the disease by genetic studies.    Credit: National Eye Institute

 

Genome-wide association studies have generated new insight into the devastating eye disease

MIT Technology Review, May 26, 2010, by Emily Singer  –  In 2005, two genetic studies of people with age-related macular degeneration (AMD)–the most common cause of blindness in people older than 65–made a surprising discovery. Research showed that defects in a gene that is an important regulator of parts of the immune system significantly increased risk of the disease. Scientists have since identified variants in several related genes that also boost risk, and which collectively account for about 50 to 60 percent of the heritability of the disorder.

At the same time that researchers identified the harmful variation linked to AMD, Gregory Hageman, now at the University of Utah, identified a protective variant found in about 20 percent of the population. “That form is so incredibly protective that people with two copies are almost guaranteed not to develop the disease,” he says. Hageman founded Optherion, a startup based in New Haven, CT, and investigated how to translate the findings into new treatments. Optherion is now producing large quantities of an engineered version of the protein and doing preclinical safety and effectiveness testing–for example, examining whether the treatment can reduce ocular deposits in mice that lack the protein, says Colin Foster, Optherion’s president. He declined to estimate when the company will begin clinical trials of the drug.

Scientists hope that these developments will prove to be an example of the benefits that can arise from a type of genetic study called genome-wide association. The genome-wide studies of macular degeneration were among the first and perhaps the biggest success for the approach, which employs specially designed chips dotted with markers to cheaply detect hundreds of thousands of the most common variations in the human genome. While these chips have allowed scientists to cheaply scan the genomes of many patients and healthy controls, the approach has come under increasing scrutiny in the last couple of years. Even huge studies of thousands of people have failed to identify the majority of the heritability of common diseases, such as type 2 diabetes or Alzheimer’s disease.

But David Altshuler, a physician and geneticist at the Broad Institute, in Cambridge, MA, and one of the primary architects of these studies, argues that this is not the best way to measure their success. Rather than using the results to design diagnostics to predict an individual risk for developing a disease, we should use genome-wide association studies to identify new drug targets, he says. And he points toward macular degeneration as an example.

Prior to the 2005 studies, few people studying macular degeneration suspected a major role for the complement immune system, which helps to clear pathogens from the body. The link between the complement factor H gene, which is a major inhibitor of the complement immune system, and other genes to macular degeneration has allowed scientists to explore the pathology of the disease in greater molecular detail. Mice lacking the protein altogether develop kidney and eye problems. (Mice don’t have maculas, so it’s impossible to accurately mimic the disease in rodents.) Human cells expressing the mutated version of the protein have altered immune function.

Hageman, who has since left Optherion, is exploring the power of the protective protein in novel ways. Because most complement factor H protein is made in the liver, his team is examining macular degeneration in people who undergo liver transplants. “We have seen cases where people who received a liver from someone with the risk form of the protein have developed macular degeneration quickly,” he says. “And we have seen a couple of cases where someone had AMD and progression was halted after receiving a liver from someone with the protective form.” But he cautions that these cases are anecdotal; researchers need to examine many more patients to see if the effect is statistically significant.

While it’s not exactly clear how alterations in the complement factor H gene boost risk for macular degeneration, scientists theorize that the mutant protein can no longer adequately control the complement immune system, perhaps triggering it to attack healthy cells rather than the pathogens it was designed to fight. “Chronic activation of complement and chronic inability to control it probably helps to explain the age-relatedness of the disease,” says Hageman.

Anand Swaroop, a researcher at the National Eye Institute, in Bethesda, MD, points out that while the complement system is important in AMD, genome-wide association studies have implicated other genes and pathways as well. “We know that in addition to the complement system, there are three or four other pathways involved, as well as environmental factors,” says Swaroop. “Those variants are clearly as important and we have no idea what they do. I think the ultimate cure will come from targeting multiple pathways.”

Eye shade: Scientists hope that new compounds that make the eye less sensitive to light will slow the buildup of yellow spots–called drusen–seen here in the center of this retinal image from a patient with macular degeneration.     Credit: National Eye Institute

 

Dampening a light-sensing reaction in the eye might slow a common cause of blindness

MIT Technology Review, by Emily Singer  –  Molecules designed to slow the production of toxic byproducts in the eye by making it less sensitive to light are now being tested in patients with macular degeneration, the leading cause of blindness in people age 50 and older. If successful, the compounds would provide a much needed therapy for the disease, which affects more than 15 million people in the United States.

In macular degeneration, cells in the center of the eye, called the macula, deteriorate. A handful of new treatments for the more severe form of the disease, known as wet AMD, have been approved in recent years. But no treatments are yet available for the dry form, which accounts for about 90 percent of cases. Some dry cases ultimately progress to the wet form, which accounts for a large part of AMD-related blindness. “If you can treat dry AMD, you can kill two birds with one stone,” both reducing early symptoms and preventing progression to the wet form, says Paul Sieving, director of the National Eye Institute, in Bethesda, MD.

While scientists are still trying to understand the causes of AMD–age is the biggest risk factor, with genetics and lifestyle factors also playing a role–a growing pool of evidence suggests that the build up of specific compounds in the eye can hasten the cellular damage that underlies the disease. These compounds accumulate in the photoreceptors–cells in the retina that detect light–during normal eye function as the light-sensitive pigments in these cells change conformation in response to photons.

One form of the photopigment, a derivative of vitamin A, is highly reactive and leaks into nearby tissue called the retinal pigment epithelium. “Over time we think these compounds are a burden for the retinal pigment epithelium, which is essential for the healthy function of the photoreceptors,” says Janet Sparrow, director of the Retinal Cell Biology Laboratory at Columbia University, in New York. “In age-related macular degeneration, particularly the dry form, these cells die, and the photoreceptors follow.”

While this reaction is vital for sight, researchers believe that slowing the cycle in the subset of photoreceptors responsible for night vision, known as rods, could slow damage without having a large impact on daytime vision. (Preliminary results suggest it can affect dark-adaptation–when our eyes adjust to low-light conditions.) “During the daytime, the rods are spinning like crazy, wasting vitamin A for no good use,” says Ryo Kubota, an ophthalmologist and founder of Acucela, a Seattle-based startup that is developing treatments for macular degeneration. “It’s like a CCD camera pointed at the sun.”

One compound developed by Acucela that is in clinical trials inhibits the enzyme that converts the photopigment in photoreceptors from one form to another. This process happens only in the eye, allowing the drug to be administered systemically without affecting other tissue, says Kubota. The company has finished initial safety testing in humans and plans to begin a clinical trial assessing the compound’s effectiveness in patients with late-stage dry macular degeneration in a few weeks. Kubota also aims to test the compound in diabetic retinopathy and Stargardt disease, a rare, genetically inherited form of macular degeneration.

A second drug that acts by a slightly different mechanism is being evaluated for macular degeneration by Sirion Therapeutics, a Florida-based pharmaceutical company. The compound is a synthetic vitamin A derivative that is thought to reduce toxin buildup by binding to one of the proteins involved in the reaction. According to preliminary results from tests of the drug in patients with late-stage dry macular degeneration, it can slow the scarring that is characteristic of the disease by 45 percent. However, scientists won’t know if the results are statistically significant until completion of the study next year. Because no treatments had been approved for dry AMD, in 2009, the U.S. Food and Drug Administration fast-tracked the drug, speeding the review process.

 

 

 

Molecular Sunglasses for Macular Degeneration

Eye sight: White dots a patient’s retina (top) are early signs of disease. In the image below these spots are identified automatically.             Credit: Ken Tobin

 

Web-connected cameras may help doctors detect a common eye disease

 

MIT Technology Review, May 2010, by Arlene Weintraub  –  Of all the complications of diabetes, few are as devastating as diabetic retinopathy, a progressive eye disease that causes blurred vision and in some patients, blindness. By the time most patients recognize something’s wrong, it’s often too late for them to be treated effectively. As a result, diabetes is the leading cause of vision loss among adults over 20. More than 12,000 new cases of blindness each year are caused by diabetic retinopathy, according to the National Institutes of Health.

An ophthalmologist and a scientist from the Department of Energy’s Oak Ridge National Laboratories in Tennessee believe they can help doctors detect diabetic retinopathy long before the disease wreaks havoc on their patients’ vision. Their startup company, Automated Medical Diagnostics (AMDx), has developed software that can detect the early signs of diabetic retinopathy by comparing digital photos of a patient’s retina to images that represent various stages of diabetic eye disease. AMDx’s founders believe their technology will enable all health workers–even those who are not trained in eye care–to take retinal scans of any patient, zap them over the Internet to AMDx’s servers, and get a diagnosis back before the patient leaves the office. “We’re trying to show we can be as accurate as a trained ophthalmologist,” says Ken Tobin, AMDx co-founder and division director of measurement science and systems engineering at Oak Ridge.

AMDx’s technology was inspired by a system that Oak Ridge scientists originally developed to help semiconductor manufacturers analyze defects in computer chips. Their software essentially teaches computers a technique called “content-based image retrieval.” The system can take a single image of a chip and then sort through giant databases of other images to find similar visual patterns–a process that some chipmakers now use to spot problems and improve manufacturing methods.

In 2005, Tobin met Edward Chaum, an ophthalmologist and professor at the University of Tennessee’s Hamilton Eye Institute in Memphis. “Less than half of diabetics are screened in any given year for retinopathy, despite the fact that they are told they need regular eye exams,” Chaum says. Many patients don’t have health insurance, he says, or they just don’t want the hassle of traveling to see yet another specialist. But Chaum and Tobin realized that if primary care doctors could do basic eye screenings on diabetic patients, they might catch many more cases of retinopathy than are being detected today.

The retina is particularly well suited to content-based image retrieval, Tobin says. Unlike other types of medical images, such as brain scans and mammograms–which are highly variable and require multiple images to create a three-dimensional effect–the retina is virtually two-dimensional and similar from one photo to another. That makes it easier for the technology to detect lesions, leaky blood vessels, swelling, and other abnormalities on the retina that can be early signs of disease. Chaum and Tobin spent five years developing algorithms that can extract information from retinal images and screen it against a database of more than 20,000 photos. AMDx doesn’t produce diagnoses but rather alerts doctors to patients who need to be referred to specialists for more in-depth testing, diagnoses and treatments.

AMDx is currently testing its system in a handful of clinics in Mississippi and Tennessee. Training doctors is easy, Chaum says, because the cameras have features like auto-focus, and they don’t require that the patients’ eyes be dilated. The photos are sent over the Internet to AMDx’s servers and automatically compared to images in its database. Chaum then checks each result manually–a process that takes about 90 seconds per case, he says.

AMDx’s goal is to ultimately turn over the entire job to its computers, but for now it must rely on Chaum’s review. That’s because some insurers–most notably Medicare and Medicaid–will only reimburse physicians for eye screenings after an ophthalmologist examines the results. Chaum and Tobin are collecting data, with the goal of proving to both regulators and insurers that their computers are as effective as Chaum at detecting disease. “The computers can handle thousands of reports a day. The bottleneck is me signing off on them,” Chaum admits.

Efforts to remotely diagnose eye diseases have been tried on a limited basis by the Veterans Administration hospitals and other institutions. Some ophthalmologists believe that if the idea catches on, they’ll be able to treat many more cases of diabetic retinopathy than they can today. “If you can teach a clinician to recognize changes in the eye, you can teach a computer to do it,” says Barrett Katz, an ophthalmologist and professor at Montefiore Medical Center and the Albert Einstein College of Medicine in the Bronx, NY. “It doesn’t take an ophthalmologist to gather these images–if anyone could do it, that would be a major step forward.”

Tobin and Chaum are on the hunt for venture capital to fund AMDx’s expansion. They hope the current focus on health reform will give them a boost, because the ongoing debate is drawing attention to the need for improving the efficiency of the health care system. “It’s not that we can’t treat diabetic retinopathy,” Chaum says. “It’s that we’re inefficient in how we screen for it.”

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