A radical form of gene therapy that remodels eye cells into light receptors holds out the promise of restoring sight to people who are completely blind. The new approach is able to create replacement photoreceptors from cells that do not normally react to light.
In early tests on blind rescue dogs with an inherited disease similar to the human condition retinitis pigmentosa, scientists were able to restore sufficient light sensitivity for the animals to distinguish between flashing and non-flashing lights.
Blind mice given the same treatment became as good at navigating a water maze as normal mice. The research, reported in the journal Proceedings of the National Academy of Sciences, sets the stage for future clinical trials in humans with degenerative eye diseases. Two components of the "hybrid" treatment involve a gene that alters non-light sensitive cells and an injected chemical "photoswitch".
US lead scientist Professor Ehud Isacoff, from the University of California at Berkeley, said: "The dog has a retina very similar to ours, much more so than mice, so when you want to bring a visual therapy to the clinic, you want to first show that it works in a large animal model of the disease.
"We've now showed that we can deliver the photoswitch and restore light response to the blind retina in the dog as well as in the mouse, and that the treatment has the same sensitivity and speed of response. We can reanimate the dog retina."
The therapy is one of a number of potential treatments for blindness at early stages of development, two of which yielded exciting trial results this year. In October scientists from the US company Ocata Therapeutics, formerly known as Advanced Cell Technology, showed that stem cell-derived retinal cells could safely be implanted into patients and improve vision in some cases.
Earlier this year scientists at Oxford University hailed trial results from a genetic therapy for choroideremia, a rare inherited cause of blindness that affects one in 50,000 people. Inserting a missing gene called REP1 prevented progression towards blindness and led to dramatic improvements in sight for two men at an advanced stage of vision loss.
The new treatment employs a virus to insert a gene into normally non-light sensitive cells in the retina that gives them the potential to "see". The gene makes a protein that acts like a lock. When the right molecular key from the photoreceptor switch is slotted into the lock, light sensitivity is turned on. At present a new injection of the photoswitch has to be made every week to maintain its effect, since the molecule is naturally removed after a period of time.
Several of the dogs have been treated and are currently undergoing tests to determine what level of light sensitivity they now have. The dogs already had the genetic disease when they were rescued from breeders and recruited for the study.
Co-author Dr William Beltran, from the University of Pennsylvania School of Veterinary Medicine in the US, said: "Use of such a clinically relevant large animal model allows us to begin tackling the next challenges on the road to translating this novel therapeutic strategy to human patients."
The therapy is said to show promise because although diseases such as RP destroy the eye's photosensitive cells, other cells in the retina are often left intact and unharmed. They include bipolar and ganglion cells, which both transmit visual nerve signals but do not contain photoreceptors.
In tests on mice, the gene was successfully inserted into almost every one of the rodent's million or so retinal ganglion cells. According to the researchers, this should be enough to restore useful vision.
"So far we can say that the treated mice can distinguish between steady light and flashing light," said Prof Isacoff. "Our next step is to figure out how good they are at telling images apart."
The scientists are also looking to see if the photoswitch can be used to activate other receptor types, including some that might allow perception of fainter light.
One of the leading scientists involved in the quest to find a treatment for RP in the UK said the research was "exciting". Professor Paul Bishop, a consultant ophthalmologist at the Manchester Royal Eye Hospital, said: "Converting non-light sensitive cells in the retina into light-sensitive cells is an exciting new approach that has potential to restore sight in people who are blind from hereditary retinal degenerations"
Prof Bishop chairs the medical advisory board of RP Fighting Blindness, a charity dedicated to funding research into a cure or treatment for the condition and providing support to those with it.
The charity's chief executive David Head said: "This is highly-credible work which has been emerging in very recent years.” The principles behind so-called 'optogenetics' are fascinating and as ever we are amazed by the research that is being carried out around the world. "We will watch developments very closely and we will certainly be making our members and patients aware of this work. "It is important to recognise that it is still at the stage of animal testing, but exciting Nnevertheless."
In early tests on blind rescue dogs with an inherited disease similar to the human condition retinitis pigmentosa, scientists were able to restore sufficient light sensitivity for the animals to distinguish between flashing and non-flashing lights.
Blind mice given the same treatment became as good at navigating a water maze as normal mice. The research, reported in the journal Proceedings of the National Academy of Sciences, sets the stage for future clinical trials in humans with degenerative eye diseases. Two components of the "hybrid" treatment involve a gene that alters non-light sensitive cells and an injected chemical "photoswitch".
US lead scientist Professor Ehud Isacoff, from the University of California at Berkeley, said: "The dog has a retina very similar to ours, much more so than mice, so when you want to bring a visual therapy to the clinic, you want to first show that it works in a large animal model of the disease.
"We've now showed that we can deliver the photoswitch and restore light response to the blind retina in the dog as well as in the mouse, and that the treatment has the same sensitivity and speed of response. We can reanimate the dog retina."
The therapy is one of a number of potential treatments for blindness at early stages of development, two of which yielded exciting trial results this year. In October scientists from the US company Ocata Therapeutics, formerly known as Advanced Cell Technology, showed that stem cell-derived retinal cells could safely be implanted into patients and improve vision in some cases.
Earlier this year scientists at Oxford University hailed trial results from a genetic therapy for choroideremia, a rare inherited cause of blindness that affects one in 50,000 people. Inserting a missing gene called REP1 prevented progression towards blindness and led to dramatic improvements in sight for two men at an advanced stage of vision loss.
The new treatment employs a virus to insert a gene into normally non-light sensitive cells in the retina that gives them the potential to "see". The gene makes a protein that acts like a lock. When the right molecular key from the photoreceptor switch is slotted into the lock, light sensitivity is turned on. At present a new injection of the photoswitch has to be made every week to maintain its effect, since the molecule is naturally removed after a period of time.
Several of the dogs have been treated and are currently undergoing tests to determine what level of light sensitivity they now have. The dogs already had the genetic disease when they were rescued from breeders and recruited for the study.
Co-author Dr William Beltran, from the University of Pennsylvania School of Veterinary Medicine in the US, said: "Use of such a clinically relevant large animal model allows us to begin tackling the next challenges on the road to translating this novel therapeutic strategy to human patients."
The therapy is said to show promise because although diseases such as RP destroy the eye's photosensitive cells, other cells in the retina are often left intact and unharmed. They include bipolar and ganglion cells, which both transmit visual nerve signals but do not contain photoreceptors.
In tests on mice, the gene was successfully inserted into almost every one of the rodent's million or so retinal ganglion cells. According to the researchers, this should be enough to restore useful vision.
"So far we can say that the treated mice can distinguish between steady light and flashing light," said Prof Isacoff. "Our next step is to figure out how good they are at telling images apart."
The scientists are also looking to see if the photoswitch can be used to activate other receptor types, including some that might allow perception of fainter light.
One of the leading scientists involved in the quest to find a treatment for RP in the UK said the research was "exciting". Professor Paul Bishop, a consultant ophthalmologist at the Manchester Royal Eye Hospital, said: "Converting non-light sensitive cells in the retina into light-sensitive cells is an exciting new approach that has potential to restore sight in people who are blind from hereditary retinal degenerations"
Prof Bishop chairs the medical advisory board of RP Fighting Blindness, a charity dedicated to funding research into a cure or treatment for the condition and providing support to those with it.
The charity's chief executive David Head said: "This is highly-credible work which has been emerging in very recent years.” The principles behind so-called 'optogenetics' are fascinating and as ever we are amazed by the research that is being carried out around the world. "We will watch developments very closely and we will certainly be making our members and patients aware of this work. "It is important to recognise that it is still at the stage of animal testing, but exciting Nnevertheless."
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