History
Karl Stargardt
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Karl Bruno Stargardt was a German ophthalmologist born in Berlin.
In 1899 he received his doctorate from the University of Kiel, where he later became chief physician at the university eye clinic. Afterwards he worked in the eye clinic at Strassburg, then becoming head of ophthalmology at Bonn. In 1923 he became the chair of ophthalmology at the University of Maburg. Stargardt discovered Stargardt's disease in 1909. |
Current Research
Although Stargardt's disease was discovered in 1909, the cause for why it occurs was not discovered until 1997. As the cause for Stargardt's disease has been already largely researched and discovered in previous decades, over the past 10 years, much of the research that has been conducted has been for what might cure Stargardt's disease. Research involving how stem cells and new technology could cure Stargardt's disease and restore vision have been explored in particular over the past decade.
Clinical Trials
There are currently many ongoing clinical trials that are underway in order to find possible cures or treatments for Stargardt’s disease. Treatments that are currently under clinical investigation include cell therapy, gene therapy, and oral therapies. Cell therapies include processes such as ones that take a sliver of skin from a patient's arm and create stem cells out of it. These stem cells are then encouraged to grow into retinas from a combination of proteins and vitamins. Once these retinas are grown, the photoreceptor cells from these retinas are extracted from the retinas and inserted into the patients retina. This will give the patient new photoreceptor cells to use to convert light into electrical signals with in order to see, therefore restoring the person's vision. However, this will not last forever. Despite this restoration in vision that the insertion of new photoreceptor cells causes, eventually these photoreceptor cells would die as well once too much A2E builds up in the eye again, causing the person's vision to worsen back to the state it was once at if no more photoreceptor cells were added to the retina. By adding new photoreceptor cells back into the retina, a person with Stargardt's disease could have their vision restored temporarily, but not have their disease cured. To cure Stargardt's disease, the defective gene that causes the disease would have to be fixed so that the processes in the eye occur as they are supposed to in order to prevent the toxic A2E from building up. This type of therapy is still being tested as scientist have not yet been able to get the retinas to completely mature. However, one day, scientist are confident they will find a way to get them to so that the vision of adults can be restored.
The same treatment has been tested, but instead of extracting and replacing dead photoreceptor cells, retinal pigmented epithelial cells have been extracted and replaced. RPE cells provide essential supportive, functions for photoreceptors. By placing healthy RPE cells into the retina, researchers think that they can save photoreceptor cells and slow or halt vision loss.
Gene therapies seem like they could one day fix the ABCA4 gene in people, curing their Stargardt's disease and at the same time restore their vision.
Genetic engineering combined with stem cells for the purpose of gene therapy is another hypothetical way that Stargardt's Disease could be treated or cured. Stem cells could be created and manipulated to grow into retinas in the process previously mentioned. While these stem cells are still growing into retinas and are still replicating, genetic engineering could then be used to correct the mutation within their DNA. This could be done by forming recombinant DNA out of a plasma and a section of DNA containing a working ABCA4 gene. A restriction enzyme would cut the needed sections of DNA out in order to gather the materials needed to make this recombinant DNA with a functional ABCA4 gene. These two new pieces of DNA could then be connected by their sticky ends and inserted into the still forming and replicating retinal cells.
The new replicating cells would all have a working ABCA4 gene. These new photoreceptor cells could then be placed into the retina. Because these cells would have a working ABCA4 gene, the phototransduction cycle would be able to complete itself. This would cause lipofuscin (essentially vitamin A) to be cleared out of the eye regularly, preventing any new cells from dying. With this method, it is possible that the eyes could then be exactly the same as they were before any new cells were inserted into them, except now they would have a working ABCA4 gene, therefore curing that person's Stargardt's disease, restoring their vision, and preventing any more photoreceptor cells from dying. One such clinical trial is called ProgSTAR.
Another example of gene therapy in clinical trial involves cloning. If a couple knows that they are carriers for the recessive gene that causes Stargardt’s disease and they are planning on having children and are afraid that their child will inherit the disease, the couple can first produce an embryo through in vitro fertilization. The embryo could then be screened of the genetic abnormality. If the embryo had the genetic abnormality, stem cells would be taken from the embryo when it is six day old. Scientist would then use genetic engineering techniques to correct the genetic abnormality. The corrected stem cell nucleus would then be inserted into an egg to form a new embryo that would then be implanted into the mother's womb. This would cause the embryo to grow into a fetus that would essentially be an identical twin of the original embryo but with the abnormal gene corrected in every one of its cells. This fetus would still be a clone, but of an entirely new individual who is a combination of both parents. The clone would be a child of both parents, like any other child, not a clone of one parent. This child would not have Stargardt's disease as a result of a combination of cloning and genetic therapy. This method would only work to cure Stargardt's disease in embryos that will later grow into adults. There is no known cure for Stargardt's disease that has been diagnosed in people who are already young children or adults. Currently this might only work with embryos, fetuses, and much less likely, infants.
Another way of restoring vision is through retinal implants. A retinal implant is a biomedical implant technology currently being developed by a number of private companies and research institutions worldwide. The implant is meant to partially restore useful vision to people who have lost their vision due to degenerative eye conditions. There are three types of retinal implants currently in clinical trials: epiretinal implants which go on the retina, subretinal implants which go behind the retina, and suprachoroidal implants, which go above the vascular choroid. Retinal implants provide the patient who gets them with low resolution images by electrically stimulating surviving retinal cells. Such images may restore specific visual abilities, such as light perception and object recognition. The practice of retinal implants are still under clinical trial.
Clinical reports to date have demonstrated mixed success, with all patients report at least some sensation of light from the electrodes, and a smaller proportion gaining more detailed visual function, such as identifying patterns of light and dark areas. The clinical reports indicate that, even with low resolution, retinal implants are potentially useful in providing crude vision to people who otherwise would not have any vision or extremely low vision. However, clinical testing in implanted subjects is somewhat limited as there are not many people yet who are willing to get retinal implants and undergo clinical testing. In addition to this, not a tremendous amount of information is known about how these retinal implants will work under different or unusual circumstances as a majority of spatial resolution simulation experiments with retinal implants have been conducted in normal controls. It remains unclear whether the low level vision provided by current retinal implants is enough to balance the risks associated with the surgical procedure, especially for subjects with intact peripheral vision. Several other aspects of retinal implants need to be addressed in future research, including the long term stability of the implants and the possibility of changes in retinal neural pathways and synapsis in response to prolonged stimulation.
The last type of treatment that is in clinical trial are oral therapies. There is a company called MitoChem Therapeutics which has identified compounds that seem to increase mitochondrial function and show potential for significantly slowing vision loss caused by different kinds of retinal degeneration. This company's goal is to determine which compounds they have found will work best in people so that their tests can move into a clinical trial. There are emerging oral treatments that are still in clinical trials for dry A.M.D. that may also be beneficial to people with Stargardt’s disease. The Foundation Fighting Blindness is working with a number of companies and individuals to bring oral treatments for Stargardt’s into clinical trials. Both conditions are caused by the buildup of toxic waste byproducts under the retina produced by the light-sensing photoreceptors, and most of these emerging treatments work by reducing the accumulation of these toxic byproducts. Two companies in particular, ReVision, is working on getting their drug, feretinide, into clinical trials, Acucela is trying to do the same with their drug, ACU-4429.
http://consults.blogs.nytimes.com/2011/09/21/experimental-treatments-for-macular-degeneration/?_r=0
The same treatment has been tested, but instead of extracting and replacing dead photoreceptor cells, retinal pigmented epithelial cells have been extracted and replaced. RPE cells provide essential supportive, functions for photoreceptors. By placing healthy RPE cells into the retina, researchers think that they can save photoreceptor cells and slow or halt vision loss.
Gene therapies seem like they could one day fix the ABCA4 gene in people, curing their Stargardt's disease and at the same time restore their vision.
Genetic engineering combined with stem cells for the purpose of gene therapy is another hypothetical way that Stargardt's Disease could be treated or cured. Stem cells could be created and manipulated to grow into retinas in the process previously mentioned. While these stem cells are still growing into retinas and are still replicating, genetic engineering could then be used to correct the mutation within their DNA. This could be done by forming recombinant DNA out of a plasma and a section of DNA containing a working ABCA4 gene. A restriction enzyme would cut the needed sections of DNA out in order to gather the materials needed to make this recombinant DNA with a functional ABCA4 gene. These two new pieces of DNA could then be connected by their sticky ends and inserted into the still forming and replicating retinal cells.
The new replicating cells would all have a working ABCA4 gene. These new photoreceptor cells could then be placed into the retina. Because these cells would have a working ABCA4 gene, the phototransduction cycle would be able to complete itself. This would cause lipofuscin (essentially vitamin A) to be cleared out of the eye regularly, preventing any new cells from dying. With this method, it is possible that the eyes could then be exactly the same as they were before any new cells were inserted into them, except now they would have a working ABCA4 gene, therefore curing that person's Stargardt's disease, restoring their vision, and preventing any more photoreceptor cells from dying. One such clinical trial is called ProgSTAR.
Another example of gene therapy in clinical trial involves cloning. If a couple knows that they are carriers for the recessive gene that causes Stargardt’s disease and they are planning on having children and are afraid that their child will inherit the disease, the couple can first produce an embryo through in vitro fertilization. The embryo could then be screened of the genetic abnormality. If the embryo had the genetic abnormality, stem cells would be taken from the embryo when it is six day old. Scientist would then use genetic engineering techniques to correct the genetic abnormality. The corrected stem cell nucleus would then be inserted into an egg to form a new embryo that would then be implanted into the mother's womb. This would cause the embryo to grow into a fetus that would essentially be an identical twin of the original embryo but with the abnormal gene corrected in every one of its cells. This fetus would still be a clone, but of an entirely new individual who is a combination of both parents. The clone would be a child of both parents, like any other child, not a clone of one parent. This child would not have Stargardt's disease as a result of a combination of cloning and genetic therapy. This method would only work to cure Stargardt's disease in embryos that will later grow into adults. There is no known cure for Stargardt's disease that has been diagnosed in people who are already young children or adults. Currently this might only work with embryos, fetuses, and much less likely, infants.
Another way of restoring vision is through retinal implants. A retinal implant is a biomedical implant technology currently being developed by a number of private companies and research institutions worldwide. The implant is meant to partially restore useful vision to people who have lost their vision due to degenerative eye conditions. There are three types of retinal implants currently in clinical trials: epiretinal implants which go on the retina, subretinal implants which go behind the retina, and suprachoroidal implants, which go above the vascular choroid. Retinal implants provide the patient who gets them with low resolution images by electrically stimulating surviving retinal cells. Such images may restore specific visual abilities, such as light perception and object recognition. The practice of retinal implants are still under clinical trial.
Clinical reports to date have demonstrated mixed success, with all patients report at least some sensation of light from the electrodes, and a smaller proportion gaining more detailed visual function, such as identifying patterns of light and dark areas. The clinical reports indicate that, even with low resolution, retinal implants are potentially useful in providing crude vision to people who otherwise would not have any vision or extremely low vision. However, clinical testing in implanted subjects is somewhat limited as there are not many people yet who are willing to get retinal implants and undergo clinical testing. In addition to this, not a tremendous amount of information is known about how these retinal implants will work under different or unusual circumstances as a majority of spatial resolution simulation experiments with retinal implants have been conducted in normal controls. It remains unclear whether the low level vision provided by current retinal implants is enough to balance the risks associated with the surgical procedure, especially for subjects with intact peripheral vision. Several other aspects of retinal implants need to be addressed in future research, including the long term stability of the implants and the possibility of changes in retinal neural pathways and synapsis in response to prolonged stimulation.
The last type of treatment that is in clinical trial are oral therapies. There is a company called MitoChem Therapeutics which has identified compounds that seem to increase mitochondrial function and show potential for significantly slowing vision loss caused by different kinds of retinal degeneration. This company's goal is to determine which compounds they have found will work best in people so that their tests can move into a clinical trial. There are emerging oral treatments that are still in clinical trials for dry A.M.D. that may also be beneficial to people with Stargardt’s disease. The Foundation Fighting Blindness is working with a number of companies and individuals to bring oral treatments for Stargardt’s into clinical trials. Both conditions are caused by the buildup of toxic waste byproducts under the retina produced by the light-sensing photoreceptors, and most of these emerging treatments work by reducing the accumulation of these toxic byproducts. Two companies in particular, ReVision, is working on getting their drug, feretinide, into clinical trials, Acucela is trying to do the same with their drug, ACU-4429.
http://consults.blogs.nytimes.com/2011/09/21/experimental-treatments-for-macular-degeneration/?_r=0