By Sandra Arcaro
When English chemist John Dalton first wrote about color blindness in 1798, he must have wondered how science would improve the quality of life for people living with the condition. Today, spectacles, contact lenses and revolutionary corrective eye surgery combat the effects of a myriad of vision disorders, yet people with color blindness still live in quiet acceptance of this common genetic disorder. Now researchers have delivered promising results by successfully treating two squirrel moneys with defective color perception using a gene therapy that could also safely eradicate color blindness in humans.
Although not a particularly debilitating condition, millions of people around the world, including 3.5 million Americans, 13 million people in India and 16 million in China, are affected by color blindness. It is a congenital problem, largely experienced by men, that renders its sufferers incapable of discerning mainly red and green hues: seemingly trivial but, in reality, a necessity for everyday practicalities such as recognizing traffic lights.
The results have come to fruition after many years of collaboration between researchers from the University of Washington and the University of Florida. As explained by William W. Hauswirth, Ph.D., a professor of ophthalmic molecular genetics at the University of Florida’s College of Medicine, the gene therapy has involved adding "red sensitivity to cone cells in animals that are born with a condition that is exactly like human color blindness.”
Hauswirth’s team developed a gene-transfer technique to produce a desired protein. In this study, the monkeys Dalton and Sam, were treated with a substance called long-wavelength opsin, a colorless protein that works in the retina to produce pigments that are sensitive to red and green. Strengthening this study’s link to a human cure is the use of human DNA to avoid having to “switch to human genes as we move toward clinical treatments,” said Hauswirth.
The research team at the University of Washington, responsible for the long-term care and post-treatment assessment of Dalton and Sam’s color blindness, developed a variation of the Cambridge Color Test, the standard vision-testing technique given to school children whereby they must identify a specific pattern of colored dots among a field of dots varying in size, color and intensity. In this study, the test was modified to perfect the way the monkeys could communicate with the researchers and “tell” them which colors they were seeing.
According to Jay Neitz, professor of ophthalmology at the University of Washington, “Nothing happened for the first 20 weeks…but we knew right away when it began to work. It was as if they woke up and saw these new colors. The treated animals unquestionably responded to colors that had (previously) been invisible to them.” It has taken more than 18 months of testing the monkeys' ability to discern 16 hues, with some varying as much as 11-fold in intensity. The monkeys were able to trace color patterns on a computer touch screen and, when they chose correctly, they were rewarded with grape juice.
Even more rewarding are the wider implications of this study for other vision disorders. For example, approximately one in 30, 000 Americans has achromatopsia, an hereditary form of blindness, which causes nearly complete color blindness and extremely poor central vision. “Those patients would be targets for almost exactly the same treatment. Even in common types of blindness such as age-related macular degeneration or diabetic retinopathy, vision could potentially be rescued by targeting cone cells,” says Hauswirth. “We’ve shown that we can cure a cone disease in a primate, and that it can be done safely. That’s extremely encouraging.”
For more information go to www.maculardegenerationassociation.org
Friday, September 25, 2009
Friday, September 18, 2009
GENE REPLACEMENT SURGERY TRIAL AT UMASS MED
By Aaron Nicodemus
WORCESTER
David Schwarte has been legally blind since birth. His life is not completely enveloped in darkness, as he can see through “a little patch of light at the corner of my eye.” To him, colors are washed out, shapes are blurry. He walks with a long cane.
Born with a rare genetic disorder called Leber Congenital Amaurosis, Mr. Schwarte, of West Lafayette, Ind., had few options for treatment until recently.
Through a clinical trial being conducted at the University of Massachusetts Medical School, 12 people with LCA are undergoing surgery to have a malfunctioning gene in their eye replaced with a normal gene. It is the only clinical trial of its kind in New England, one of only a handful being conducted nationwide. While the procedure is not approved by the U.S. Food and Drug Administration, the first phase of trials established that the procedure is safe. The trial is sponsored by Applied Genetic Technologies Corp. of Gainesville, Fla.
It is hoped that the trial will lead to a treatment for the estimated 20,000 to 40,000 people worldwide who have LCA.
Mr. Schwarte has been coming to Worcester regularly since July, when he had the surgery. So far, he has seen a slight improvement in his peripheral vision, and that sight is slowly moving toward the center of his eye.
“I'm still in the healing stage,” he said recently.
Dr. Shalesh Kaushal, who joined the medical school in January as its chair of ophthalmology, described the vision of people with LCA as seeing shapes and shadows, as having most colors washed out. People with LCA typically lose their vision in the first months of their lives.
“A cloudy day for most people would be like sitting in a darkened movie theater for people with LCA,” he said. “And it's a progressive disease, meaning they will continue to lose their sight over time.”
He said that gene therapy, once it has been sufficiently tested, may one day be available to address any number of gene-related disorders and diseases.
“It's a type of transforming medicine that is made possible by a confluence of a set of events,” Dr. Kaushal said. “There is any number of applications possible.”
The reason researchers have focused on curing a rare disease such as LCA, he explained, is not because it is the most common but because it is the most treatable. LCA is caused by a mutation within a single gene. Because the gene can be isolated in the eye, it can be manipulated. The exact same type of disease can be found in mice and dogs, giving scientists nonhuman test subjects.
The final piece was the development of a human virus that does not cause a disease that can be injected — with the corrected gene inside — behind the retina. The virus causes a mild immune response in most patients, he said.
Interestingly, said Dr. Kaushal, the retina's lack of an immune response works in its favor.
“When a foreign substance is introduced into human tissues and cells, it triggers the body's immune system,” he said. “Stimulation of the body's immune system can inhibit the effectiveness of gene therapy treatments and, in some cases can have adverse effects on the body and other healthy tissues. However, the retina lacks an immune mechanism, which makes treating eye diseases with gene therapy possible.”
Once the virus with the normal gene is delivered behind the patient's retina, the patient's body activates the gene. The gene then begins producing the protein necessary for the rods and cones inside the eye to recognize light. With the malfunctioning gene, LCA patients do not produce enough of this protein, and therefore their eyes do not respond to light.
Dr. Kaushal joined the medical school in January, coming from the University of Florida where he was assistant professor of ophthalmology. He is one of the first researchers in the United States to use gene therapy to treat LCA. At Florida, he and Dr. Terence R. Flotte, now dean of the University of Massachusetts Medical School, had collaborated on earlier clinical trials for this disorder.
Dr. Kaushal is a member of the Gene Therapy Center, part of the Advanced Therapeutics Cluster at the medical school. Research at the center is being applied to diseases such as cystic fibrosis; a genetic lung and liver disorder called alpha-1 antitrypsin deficiency; inherited metabolic disorders such as lysosomal storage disease; a progressive nerve disease called Canavan disease; also eye disorders such as retinal and macular degeneration.
During initial clinical trials at the University of Florida, Dr. Kaushal said all of the LCA patients saw improvement in their vision. One patient was able to read the digital clock in her parents' minivan for the first time.
“I remember one patient taking me aside and saying to me, ‘Doctor, I never knew the sky was so blue,' ” he said. “That was confirmation to me that we're on the right path.”
For more information go to www.maculardegenerationassociation.org
WORCESTER
David Schwarte has been legally blind since birth. His life is not completely enveloped in darkness, as he can see through “a little patch of light at the corner of my eye.” To him, colors are washed out, shapes are blurry. He walks with a long cane.
Born with a rare genetic disorder called Leber Congenital Amaurosis, Mr. Schwarte, of West Lafayette, Ind., had few options for treatment until recently.
Through a clinical trial being conducted at the University of Massachusetts Medical School, 12 people with LCA are undergoing surgery to have a malfunctioning gene in their eye replaced with a normal gene. It is the only clinical trial of its kind in New England, one of only a handful being conducted nationwide. While the procedure is not approved by the U.S. Food and Drug Administration, the first phase of trials established that the procedure is safe. The trial is sponsored by Applied Genetic Technologies Corp. of Gainesville, Fla.
It is hoped that the trial will lead to a treatment for the estimated 20,000 to 40,000 people worldwide who have LCA.
Mr. Schwarte has been coming to Worcester regularly since July, when he had the surgery. So far, he has seen a slight improvement in his peripheral vision, and that sight is slowly moving toward the center of his eye.
“I'm still in the healing stage,” he said recently.
Dr. Shalesh Kaushal, who joined the medical school in January as its chair of ophthalmology, described the vision of people with LCA as seeing shapes and shadows, as having most colors washed out. People with LCA typically lose their vision in the first months of their lives.
“A cloudy day for most people would be like sitting in a darkened movie theater for people with LCA,” he said. “And it's a progressive disease, meaning they will continue to lose their sight over time.”
He said that gene therapy, once it has been sufficiently tested, may one day be available to address any number of gene-related disorders and diseases.
“It's a type of transforming medicine that is made possible by a confluence of a set of events,” Dr. Kaushal said. “There is any number of applications possible.”
The reason researchers have focused on curing a rare disease such as LCA, he explained, is not because it is the most common but because it is the most treatable. LCA is caused by a mutation within a single gene. Because the gene can be isolated in the eye, it can be manipulated. The exact same type of disease can be found in mice and dogs, giving scientists nonhuman test subjects.
The final piece was the development of a human virus that does not cause a disease that can be injected — with the corrected gene inside — behind the retina. The virus causes a mild immune response in most patients, he said.
Interestingly, said Dr. Kaushal, the retina's lack of an immune response works in its favor.
“When a foreign substance is introduced into human tissues and cells, it triggers the body's immune system,” he said. “Stimulation of the body's immune system can inhibit the effectiveness of gene therapy treatments and, in some cases can have adverse effects on the body and other healthy tissues. However, the retina lacks an immune mechanism, which makes treating eye diseases with gene therapy possible.”
Once the virus with the normal gene is delivered behind the patient's retina, the patient's body activates the gene. The gene then begins producing the protein necessary for the rods and cones inside the eye to recognize light. With the malfunctioning gene, LCA patients do not produce enough of this protein, and therefore their eyes do not respond to light.
Dr. Kaushal joined the medical school in January, coming from the University of Florida where he was assistant professor of ophthalmology. He is one of the first researchers in the United States to use gene therapy to treat LCA. At Florida, he and Dr. Terence R. Flotte, now dean of the University of Massachusetts Medical School, had collaborated on earlier clinical trials for this disorder.
Dr. Kaushal is a member of the Gene Therapy Center, part of the Advanced Therapeutics Cluster at the medical school. Research at the center is being applied to diseases such as cystic fibrosis; a genetic lung and liver disorder called alpha-1 antitrypsin deficiency; inherited metabolic disorders such as lysosomal storage disease; a progressive nerve disease called Canavan disease; also eye disorders such as retinal and macular degeneration.
During initial clinical trials at the University of Florida, Dr. Kaushal said all of the LCA patients saw improvement in their vision. One patient was able to read the digital clock in her parents' minivan for the first time.
“I remember one patient taking me aside and saying to me, ‘Doctor, I never knew the sky was so blue,' ” he said. “That was confirmation to me that we're on the right path.”
For more information go to www.maculardegenerationassociation.org
Wednesday, September 9, 2009
New therapies slows vision loss
When Albert Budacz was young, he prided himself on having good eyesight; he never wore glasses. But as he eased into his late 40s, he couldn't see as well.
"I noticed a change in my vision," he explained. "Primarily in church when I would open a Bible, or something like that, I had to position myself under a light to see it."
Ophthalmologist Dr. Sharon Solomon examined Albert Budacz and found age-related macular degeneration.
Concerned that he was beginning to lose his sight, Budacz went to his ophthalmologist, Dr. Sharon Solomon with the Wilmer Eye Institute at Johns Hopkins. He was found to have the beginnings macular degeneration, an eye condition that occurs when the central portion of the retina, called the macula, begins to deteriorate.
Until recently, people with age-related macular degeneration, the leading cause of severe vision loss in Americans older than 60, had few treatment options. But now, thanks to new research and advancing technology, there are more vision-saving choices.
Early signs of macular degeneration-related vision loss include shadowy areas or fuzzy distortion in a person's central vision.
"A patient told me recently that he noticed when he was driving that the streetlights were slanted; the poles themselves were slanted," Solomon said. "That's a classic sign of the beginning of this disease."
Although obesity, smoking, high blood pressure and certain drugs can cause it, age is the primary risk factor.
"As people approach their 50s and later, they may have little yellow deposits that develop underneath the retina, and that's called drusen," Solomon explained. "Those deposits are the hallmark of what we call early age-related macular degeneration."
There are two forms of age-related macular degeneration, or AMD: the dry form, known as non-neovascular, and the wet form, called neovascular. The dry form, which Budacz has, is more common. According to the National Eye Institute, about 85 to 90 percent of patients with advanced macular degeneration have the dry form.
Dry macular degeneration is caused when drusen begin to accumulate in and around the macula. Drusen, those yellowish deposits, are debris from deteriorating tissue. With dry AMD, there is usually a gradual loss of central vision. Over a period of years, dry AMD can progress to a gradual deterioration of retinal cells, which can result in severe vision loss or lead to the wet version of AMD.
As of now, there is no FDA-approved treatment for dry macular degeneration, although a few drugs and devices are in clinical trials. However, studies have shown that supplements and a healthy diet can slow the progression of dry macular degeneration. A recent National Eye Institute study found that certain nutrients such as beta carotene (vitamin A) and vitamins C and E may reduce the risk of progression of early-stage AMD by 25 percent.
Solomon says these antioxidants have a positive effect. "They're known as 'preservision,' " she said, noting that they are commonly given to certain patient groups to slow their progression to advanced macular degeneration.
Other research has shown that B6, B12 and folic acid may help prevent age-related macular degeneration. In a study of more than 5,000 women, researchers noted those who took a combination of B6 and B12 vitamins along with a folic acid supplement had a 34 percent lower risk of developing AMD then those taking a placebo.
Although the studies showed strong results, the American Academy of Ophthalmology cautions patients to talk to their eye doctors about which supplements are best for their condition before they start popping vitamins.
In the wet version of macular degeneration, abnormal blood vessels grow beneath the retina and leak blood and fluid. This leakage causes permanent damage to light-sensitive retinal cells, which die off and create blind spots in central vision.
Doctors say it's the body's misguided way of attempting to supply the retina with more nutrients and oxygen. Instead, the attempt creates scarring, leading to severe central vision loss.
Up until recently, there's been very little doctors could do for the wet form of macular degeneration. But over the past decade, there have been a few treatments developed to slow its progression. Cold lasers are now used to freeze the abnormal blood vessels responsible for destroying the macula; they have a 60 percent success rate.
And within the past three years, researchers pinpointed a protein in the eye, called vascular endothelial growth factor, that stimulates the development of blood vessels. Injectable drugs that inhibit VEGF are now FDA-approved and available; without VEGF, there is little to encourage the growth of blood vessels in the retina.
"They actually have a 90 percent chance of stabilizing vision and a 30 to 40 percent chance of improving vision," Solomon said. "This is the first therapy that we've had that can actually [reverse] vision loss."
Most ophthalmologists prefer an ounce of prevention to a pound of cure. They promote yearly eye exams as the easiest way to keep macular degeneration in check -- and warn against waiting for a crisis to schedule a checkup.
"We typically pick up a patient when, all of a sudden, they've had an acute, abrupt loss of vision or change in the quality of their vision," Solomon said. "And sometimes it's too late."
Albert Budacz was lucky. He caught his macular degeneration in time. He's stopped smoking and takes antioxidants to slow the progression of the disease.
And although he may not have the eyesight he had as a young man, he can still see pretty well with or without glasses. And to him, that's all that matters.
For more information go to: www.maculardegenerationassociation.org
"I noticed a change in my vision," he explained. "Primarily in church when I would open a Bible, or something like that, I had to position myself under a light to see it."
Ophthalmologist Dr. Sharon Solomon examined Albert Budacz and found age-related macular degeneration.
Concerned that he was beginning to lose his sight, Budacz went to his ophthalmologist, Dr. Sharon Solomon with the Wilmer Eye Institute at Johns Hopkins. He was found to have the beginnings macular degeneration, an eye condition that occurs when the central portion of the retina, called the macula, begins to deteriorate.
Until recently, people with age-related macular degeneration, the leading cause of severe vision loss in Americans older than 60, had few treatment options. But now, thanks to new research and advancing technology, there are more vision-saving choices.
Early signs of macular degeneration-related vision loss include shadowy areas or fuzzy distortion in a person's central vision.
"A patient told me recently that he noticed when he was driving that the streetlights were slanted; the poles themselves were slanted," Solomon said. "That's a classic sign of the beginning of this disease."
Although obesity, smoking, high blood pressure and certain drugs can cause it, age is the primary risk factor.
"As people approach their 50s and later, they may have little yellow deposits that develop underneath the retina, and that's called drusen," Solomon explained. "Those deposits are the hallmark of what we call early age-related macular degeneration."
There are two forms of age-related macular degeneration, or AMD: the dry form, known as non-neovascular, and the wet form, called neovascular. The dry form, which Budacz has, is more common. According to the National Eye Institute, about 85 to 90 percent of patients with advanced macular degeneration have the dry form.
Dry macular degeneration is caused when drusen begin to accumulate in and around the macula. Drusen, those yellowish deposits, are debris from deteriorating tissue. With dry AMD, there is usually a gradual loss of central vision. Over a period of years, dry AMD can progress to a gradual deterioration of retinal cells, which can result in severe vision loss or lead to the wet version of AMD.
As of now, there is no FDA-approved treatment for dry macular degeneration, although a few drugs and devices are in clinical trials. However, studies have shown that supplements and a healthy diet can slow the progression of dry macular degeneration. A recent National Eye Institute study found that certain nutrients such as beta carotene (vitamin A) and vitamins C and E may reduce the risk of progression of early-stage AMD by 25 percent.
Solomon says these antioxidants have a positive effect. "They're known as 'preservision,' " she said, noting that they are commonly given to certain patient groups to slow their progression to advanced macular degeneration.
Other research has shown that B6, B12 and folic acid may help prevent age-related macular degeneration. In a study of more than 5,000 women, researchers noted those who took a combination of B6 and B12 vitamins along with a folic acid supplement had a 34 percent lower risk of developing AMD then those taking a placebo.
Although the studies showed strong results, the American Academy of Ophthalmology cautions patients to talk to their eye doctors about which supplements are best for their condition before they start popping vitamins.
In the wet version of macular degeneration, abnormal blood vessels grow beneath the retina and leak blood and fluid. This leakage causes permanent damage to light-sensitive retinal cells, which die off and create blind spots in central vision.
Doctors say it's the body's misguided way of attempting to supply the retina with more nutrients and oxygen. Instead, the attempt creates scarring, leading to severe central vision loss.
Up until recently, there's been very little doctors could do for the wet form of macular degeneration. But over the past decade, there have been a few treatments developed to slow its progression. Cold lasers are now used to freeze the abnormal blood vessels responsible for destroying the macula; they have a 60 percent success rate.
And within the past three years, researchers pinpointed a protein in the eye, called vascular endothelial growth factor, that stimulates the development of blood vessels. Injectable drugs that inhibit VEGF are now FDA-approved and available; without VEGF, there is little to encourage the growth of blood vessels in the retina.
"They actually have a 90 percent chance of stabilizing vision and a 30 to 40 percent chance of improving vision," Solomon said. "This is the first therapy that we've had that can actually [reverse] vision loss."
Most ophthalmologists prefer an ounce of prevention to a pound of cure. They promote yearly eye exams as the easiest way to keep macular degeneration in check -- and warn against waiting for a crisis to schedule a checkup.
"We typically pick up a patient when, all of a sudden, they've had an acute, abrupt loss of vision or change in the quality of their vision," Solomon said. "And sometimes it's too late."
Albert Budacz was lucky. He caught his macular degeneration in time. He's stopped smoking and takes antioxidants to slow the progression of the disease.
And although he may not have the eyesight he had as a young man, he can still see pretty well with or without glasses. And to him, that's all that matters.
For more information go to: www.maculardegenerationassociation.org
Wednesday, September 2, 2009
ANV therapy system receives CE mark approval
Fremont, CA—NeoVista Inc. received approval from BSI Product Services to apply the CE mark to its anti-neovascular (ANV) therapy system (Vidion) to treat wet age-related macular degeneration (AMD), the company announced.
The epimacular brachytherapy device is said to be the first of its kind to receive commercial approval, according to a statement issued by the company, and it has significant implications for neovascular AMD treatment. The CE mark provides NeoVista with the ability to sell the device in all European Union (EU) countries.
“This is a momentous occasion for NeoVista as we look forward to bringing our technology to the EU with this first essential step towards commercialization,” said John N. Hendrick, president and chief executive officer, NeoVista.
“With this approval, we will begin working with our distributor network to make available our technology to the multitude of European patients currently suffering from wet AMD who are seeking an effective therapeutic option that can potentially offer a better quality of life to the patient and decrease the current burden of treatment,” Hendrick added.
The ANV therapy system delivers targeted beta radiation to leaking blood vessels, which affect central vision, without causing damage to the surrounding tissues, according to the company. This targeted epimacular brachytherapy has shown promising clinical results in preliminary clinical trials, the company said.
The epimacular brachytherapy device is said to be the first of its kind to receive commercial approval, according to a statement issued by the company, and it has significant implications for neovascular AMD treatment. The CE mark provides NeoVista with the ability to sell the device in all European Union (EU) countries.
“This is a momentous occasion for NeoVista as we look forward to bringing our technology to the EU with this first essential step towards commercialization,” said John N. Hendrick, president and chief executive officer, NeoVista.
“With this approval, we will begin working with our distributor network to make available our technology to the multitude of European patients currently suffering from wet AMD who are seeking an effective therapeutic option that can potentially offer a better quality of life to the patient and decrease the current burden of treatment,” Hendrick added.
The ANV therapy system delivers targeted beta radiation to leaking blood vessels, which affect central vision, without causing damage to the surrounding tissues, according to the company. This targeted epimacular brachytherapy has shown promising clinical results in preliminary clinical trials, the company said.
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