Gene therapy shows promise for reversing blindness
(3 October 2017)
Researchers at Oxford University have shown how it might be possible to reverse blindness using gene therapy to reprogram cells at the back of the eye to become light sensitive.
Most causes of untreatable blindness occur due to loss of the millions of light sensitive photoreceptor cells that line the retina, similar to the pixels in a digital camera.
[...] In a new laboratory study in Oxford, Samantha de Silva and colleagues used a modified virus to inject a new gene into these cells, which then express a light sensitive protein, melanopsin, in the residual retinal cells in mice which were blind from retinitis pigmentosa.
The mice were monitored for over a year and they maintained vision during this time, being able to recognise objects in their environment which indicated a high level of visual perception. The cells expressing melanopsin were able to respond to light and send visual signals to the brain. The Oxford team has also been trialling an electronic retina successfully in blind patients, but the genetic approach may have advantages in being simpler to administer.
The research was led by Professors Robert MacLaren and Mark Hankins at the Nuffield Laboratory of Ophthalmology in Oxford. Samantha de Silva, the lead author of the study said: ‘There are many blind patients in our clinics and the ability to give them some sight back with a relatively simple genetic procedure is very exciting. Our next step will be to start a clinical trial to assess this in patients.’
[...] Robert MacLaren added: ‘The effect of retinitis pigmentosa on families with the disease is devastating and we have spent many years working out new ways to slow the loss of sight and to begin restoring it. This new approach is exciting because by using a human protein that is already present in the eye we reduce the chances of causing an immune response.’
New trial for blindness rewrites the genetic code
(17 March 2017)
Researchers have started a new gene therapy clinical trial to treat X-linked retinitis pigmentosa (XLRP), the most common cause of blindness in young people.
[...] Gene therapy uses a virus to insert the correct copy of a defective gene into cells, and has shown promise for treating genetic causes of blindness. Unfortunately, the gene involved with retinitis pigmentosa, RPGR, is highly unstable, making gene therapy particularly challenging. The RPGR gene’s unusual genetic code has made it very difficult to work with in the laboratory.
However, a research team led by Professor Robert MacLaren from the University of Oxford has reprogrammed the genetic code of RPGR to make it more stable, but in a way that does not affect its function. This has allowed the gene to be delivered reliably by a viral vector into retinal cells.
The current trial is the first in the world to test a treatment for retinitis pigmentosa caused by RPGR.
Robert MacLaren, Professor of Ophthalmology at the University of Oxford, who is leading the trial said: 'The effect of RPGR-related disease on families with retinitis pigmentosa is devastating and we have spent many years working out how to develop this gene therapy. Changing the genetic code is always undertaken with great caution, but the new sequence we are using has proven to be highly effective in our laboratory studies.
'The genetic code for all life on Earth is made up of four letters – G, T, A and C. In RPGR, however, half of the gene comprises only two letters – A and G. This makes the gene very unstable and prone to mutations, making it a lead cause of blindness in patients with retinitis pigmentosa. RPGR is vital for the light sensitive cells at the back of the eye.'
Researchers continue the fight against Choroideremia
(8 November 2016)
Following on from a successful world’s first Phase I gene therapy trial for choroideremia, Professor Robert MacLaren and his team have started a Phase II trial enrolling 30 patients. The project has been funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and NIHR partnership.
In this trial, Professor MacLaren is using an operating microscope with integrated optical coherence tomography (OCT) that will refine the surgery that is integral to the gene replacement therapy. The purchase of this vital piece of equipment called OPMI Lumera 700 Rescan is thanks to a number of funders including: Fight for Sight, Tommy Salisbury Choroideremia Fund at Fight for Sight, National Eye Research Centre, Choroideremia Research Foundation USA, Saturday Hospital Fund and benefactors of the MacLaren Group.
Choroideremia, is an incurable genetic condition affecting approximately 50,000 men worldwide. It is caused by a genetic fault in the REP-1 gene and gene therapy is being trialled to replace the faulty gene with a healthy one. The intraoperative OCT microscope enables surgeons to track changes in the retinal anatomy in real time and thereby permit safe and precise delivery of the gene therapy with the ultimate goal of improved vision for patients.
[...] Professor of Ophthalmology at University of Oxford Robert MacLaren said: “On behalf of the Clinical Ophthalmology Research Group at the University of Oxford I would like to thank all its generous benefactors for assisting us in raising funds for an OCT operating microscope for the Oxford Eye Hospital. The equipment is being used in exciting new gene therapies for the treatment of patients suffering from incurable eye conditions.
“By using the OCT operating microscope it allows for better and safer outcomes for patients due to more refined surgery using the microscope. If successful, this trial can be translated to other conditions such as retinitis pigmentosa, which affects 1 in 4,000 people.”
World first for robot eye operation
(12 September 2016)
Surgeons at Oxford's John Radcliffe Hospital have performed the world's first operation inside the eye using a robot.
Robert MacLaren, Professor of Ophthalmology assisted by Dr Thomas Edwards, Nuffield Medical Fellow, used the remotely controlled robot to lift a membrane 100th of a millimetre thick from the retina at the back of the right eye of the Reverend Dr William Beaver, 70, an Associate Priest at St Mary the Virgin, Iffley, Oxford. He is the first patient ever to undergo this experimental procedure.
[...] On completing the operation, Professor Robert MacLaren said: "There is no doubt in my mind that we have just witnessed a vision of eye surgery in the future.
"Current technology with laser scanners and microscopes allows us to monitor retinal diseases at the microscopic level, but the things we see are beyond the physiological limit of what the human hand can operate on. With a robotic system, we open up a whole new chapter of eye operations that currently cannot be performed."
Speaking at his follow up visit at the Oxford Eye Hospital, Father Beaver said, "My sight is coming back. I am delighted that my surgery went so well and I feel honoured to be part of this pioneering research project."
Professor MacLaren added, "This will help to develop novel surgical treatments for blindness, such as gene therapy and stem cells, which need to be inserted under the retina with a high degree of precision."
Gene therapy restores sight in people with inherited blindness
(29 April 2016)
Researchers at the University of Oxford have found gene therapy can return some sight to people with inherited blindness for up to four years after treatment.
Scientists used gene therapy to treat people with choroideremia – a genetic disease causing progressive loss of vision, and eventually complete blindness.
They injected a harmless virus directly into the eye to replace the gene missing in people with choroideremia. Four years after treatment, two of the six people on the trial had much better vision, and three had no deterioration in their treated eyes.
Professor Robert MacLaren, who led the study, said this seemingly permanent effect “is the breakthrough we have all been waiting for”.
It’s hoped gene therapy could restore sight in people with other types of inherited blindness, including retinitis pigmentosa, and age-related macular degeneration.
Wellcome funded the study, published this week in the New England Journal of Medicine through our Health Innovation Challenge Fund in partnership with NIHR.
A follow-on trial of 30 further patients will now take place.
Gene therapy development shows long term benefit for treating rare blindness
(29 April 2016)
The EME Programme has funded further research into a pioneering gene therapy to treat a rare form of blindness after previous research found that the technique has helped improve the vision of some patients for as long as four years.
A technique which involves injecting a virus into the eye to deliver billions of healthy genes to replace a key missing gene for choroideremia sufferers has provided sustained improvement in vision for up four years for some patients. This provides the strongest evidence so far that the effects of gene therapy are potentially permanent and could therefore provide a single treatment cure for many types of inherited blindness, including retinitis pigmentosa and age-related macular degeneration.
[...] Professor Robert MacLaren, the lead investigator of the study, said: “There have recently been questions about the long term efficacy of gene therapy, but now we have unequivocal proof that the effects following a single injection of viral vector are sustained.
“Gene therapy is a new technique in medicine that has great potential. As we learn more about genetics we realise that correcting faulty genes even before a disease starts may be the most effective treatment for a number of ailments. Gene therapy uses the infectious properties of a virus to insert DNA into a cell, but the viral DNA is removed and replaced with DNA that is reprogrammed in the lab to correct whichever gene is faulty in the patient.
“In this case, success in getting a treatment effect that lasts at least several years was achieved because the viral DNA had an optimal design and the viral vector was delivered into the correct place, using advanced surgical techniques. In brief, this is the breakthrough we have all been waiting for.”
Gene therapy shows long-term benefit for treating rare blindness
(29 April 2016)
A technique which involves injecting a virus into the eye to deliver billions of healthy genes to replace a key missing gene for choroideremia sufferers has provided sustained improvement in vision for up four years for some patients.
This provides the strongest evidence so far in humans that the effects of gene therapy are potentially permanent and could therefore provide a single treatment cure for many types of inherited blindness. These include retinitis pigmentosa, which affects young people, and age-related macular degeneration, which affects the older age group.
Reporting the results this week in the New England Journal of Medicine, doctors from the University of Oxford examined the vision of six patients up to four years after receiving gene therapy at Oxford's John Radcliffe Hospital. These six were the first in the world to have the procedure for choroideremia in a trial funded by the Department of Health and the Wellcome Trust.
[...] Professor Robert MacLaren, the lead investigator of the study, said: 'There have recently been questions about the long term efficacy of gene therapy, but now we have unequivocal proof that the effects following a single injection of viral vector are sustained. Even sharpening up the little bit of central vision that these patients have can give them considerable independence.
'Gene therapy is a new technique in medicine that has great potential. As we learn more about genetics we realise that correcting faulty genes even before a disease starts may be the most effective treatment. Gene therapy uses the infectious properties of a virus to insert DNA into a cell, but the virial DNA is removed and replaced with DNA that is reprogrammed in the lab to correct whichever gene is faulty in the patient.
'In this case, success in getting a treatment effect that lasts at least several years was achieved because the viral DNA had an optimal design and the viral vector was delivered into the correct place, using advanced surgical techniques. In brief, this is the breakthrough we have all been waiting for.'
Dr Stephen Caddick, Director of Innovation at the Wellcome Trust, added: 'To permanently restore sight to people with inherited blindness would be a remarkable medical achievement.
'This is the first time we’ve seen what appears to be a permanent change in vision after just one round of treatment. It’s a real step forwards towards an era where gene therapy is part of routine care for these patients.'
Partnership to test robotic surgical system
(1 March 2016)
Oxford University has signed an agreement with Dutch medical robotics firm Preceyes to test a robotic surgical system. A team led by eye surgeon and researcher Professor Robert MacLaren will run human clinical trials using the PRECEYES Surgical System. The study will assess the clinical functionality and applicability of the device, focusing on high-precision vitreoretinal surgery - operations which take place at the back of the eye. The aim is for the trial results to facilitate future targeted drug delivery.
Separately, Preceyes have signed a deal with Oxford University spin-out company Nightstar, to collaborate in the development of a high-precision drug delivery technology in the eye. Nightstar will use the Preceyes robotic device to further refine the delivery of gene therapy to the subretinal space - the area behind the retina in the eye.
Preceyes' high-precision robotic system targets ocular surgery, with vitreoretinal surgical procedures as the initial target market. The technology promises to improve the delivery of existing ocular surgery as well as enables the development of new treatments such as high-precision drug delivery, assisting eye surgeons in performing the most demanding surgical tasks.
[...] Robert MacLaren, Professor of Ophthalmology at the University of Oxford commented: '“Over the last century, devices that enhance surgical precision have given us the greatest breakthroughs in ophthalmology. We are delighted to have approval for a clinical trial in Oxford which will be the first to assess use of a robotic device for surgery inside the eye.'
Blind woman’s joy as she is able to read the time thanks to 'bionic eye'
(5 January 2016)
A patient who is the first in the UK to receive the world’s most advanced 'bionic eye' has been able to read the time for the first time in more than five years.
[...] Professor Robert MacLaren, who is leading the trial, said: 'Restoring sight to the blind using an electronic device presents huge challenges for the technology, the surgery and above all, the patient. But at the same time, we know the huge potential benefit if we can get it right. I am delighted that the trial has started so successfully with the excellent results we have had so far with Rhian.
'For a blind person having independence is a very important aspect of their vision so if we can give someone enough vision so that they can see where they are in the home, they can go out, they can walk to the bus stop, they can go out and they can see people around them, they're basically aware of their surroundings then we've achieved a great deal.
'It may not be enough to read things yet, but just enough to navigate would be sufficient. And also you must not forget that we're at the very beginning of a very exciting technology.'
'It's an amazing process because what Rhian and others are trying to do is reactivate a part of the brain that hasn't been doing anything for the last 10 years or so and there is a lot of rehabilitation because basically they are learning to see again.'
Minister for Life Sciences, George Freeman MP, said: "This ground-breaking research to create the world's most advanced bionic eye highlights the crucial role of the NHS as a test bed for 21st century medicine.
"In investing over £1 billion a year into the National Institute for Health Research, we are helping to translate scientific advances into real benefits for patients."
Bascom Palmer Eye Institute Initiates Pioneering Gene Therapy Targeting Choroideremia
(17 November 2015)
A research team at Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine has performed gene therapy on a 47-year-old man as part of a Phase 2 clinical trial to treat Choroideremia (CHM), a rare inherited cause of blindness. The Food and Drug Administration approved clinical trial will ultimately treat six patients with CHM to help determine the safety and efficacy of this novel treatment. A promising treatment for CHM had been elusive until the advent of gene therapy. The transfer of new genes into the dysfunctional cells has the potential to restore the health and function of these cells.
[...] The clinical trial’s approach involved using a large number of harmless viruses (known as AAV2-REP1) modified to carry copies of the normal gene into the eye to correct the genetic defect in CHM. The gene therapy was delivered to the space under the retina through an injection technique approved by the FDA for research purposes for this clinical trial. The injection provides controlled delivery of the gene therapy. The modified viruses infect retinal cells and carry copies of the normal gene into the cells, where the normal gene continues to work to maintain the function and integrity of the cells. The goal of the treatment is to maintain or even improve visual function in CHM patients.
[...] The first clinical trial using the AAV2-REP1 approach to treat CHM was conducted at the University of Oxford under the direction of Dr. Robert MacLaren, a professor of ophthalmology. MacLaren and the Bascom Palmer team have collaborated on this project for the past year.
£23 million boost for Oxford spinout company
(9 November 2015)
NightstaRx Ltd (Nightstar), a biopharmaceutical company spun out from the University of Oxford specialising in developing gene therapies for inherited retinal dystrophies, has announced that it has completed a $35 million (£23.2 million) funding round. The round was led by New Enterprise Associates (NEA), one of the world’s leading venture capital firms.
[...] Nightstar’s lead programme is a gene therapy for an inherited form of progressive blindness, choroideremia, developed by Professor Robert MacLaren at Oxford’s Nuffield Laboratory of Ophthalmology. The therapy has shown promising results in a clinical trial, which was published in the Lancet in January 2014. This approach uses a genetically modified virus to deliver an unmutated copy of the relevant gene into the retinal cells of choroideremia patients.
[...] Robert MacLaren, Professor of Ophthalmology at the University of Oxford said: 'Gene therapy has huge potential as a treatment for many patients who are suffering from retinitis pigmentosa and other genetic forms of blindness. We have established an internationally renowned team around the choroideremia programme and I am delighted that this additional funding will allow us to develop our other retinal gene therapy projects into real treatments for patients.'
Gene therapy trial as a treatment for choroideremia
(24 July 2015)
A clinical trial, funded by the Efficacy and Mechanism Evaluation (EME) programme, an MRC and NIHR partnership, will investigate if a new gene therapy treatment can restore the vision or prevent progressive vision loss for people with choroideremia.
Normally affecting males, choroideremia is an inherited disease of the eye leading to progressive loss of sight and blindness. It occurs when a mutated gene, CHM, causes a slow degeneration of the cells in the light sensitive layer at the back of the eye known as the retina. The condition is currently incurable.
The trial will attempt to replace the mutated gene with a normal CHM gene in the retinal cells of patients with choroideremia. Due to the fragile structure of genes, it is not possible to inject a replacement gene directly into the nucleus of a cell where genes are stored. To overcome this, a genetically modified virus, containing a CHM gene, will be injected under the retina where it will carry the replacement gene into the nucleus of the patient’s retinal cells.
[...] Lead researcher Professor Robert E MacLaren from the University of Oxford said:
“Developing a treatment for an eye disease that has been incurable since it was first identified 140 years ago would represent a huge achievement for NHS research. Gene therapy has great potential for treating retinal degenerations and we are delighted that this award will enable us to take the final steps towards regulatory approval”
Gene therapy gives long-term protection to photoreceptor cells in a mouse model of retinitis pigmentosa
(15 July 2015)
[...] Retinitis pigmentosa (RP) affects 1 in 4000 people, with symptoms that typically appear between age 10 and 30. Night vision and peripheral vision go first, as the photoreceptors active in low light – the 'rods' – start to degenerate. Eventually the condition affects the 'cones' – the photoreceptors responsible for central, detailed, colour vision.
The current study looked at a mouse model of retinitis pigmentosa in which the mice lack rhodopsin – the main pigment in rod photoreceptors. At age 4 weeks – after rod degeneration was underway and before cones were affected – the mice were dosed with a virus modified to produce human ciliary neurotrophic factor (CNTF) protein in the retina.
[...] Treatment was given to one eye, while saline was given to the other eye as a control. At 8 weeks, non-invasive imaging showed similar numbers of cones in all treated and untreated eyes. However, the number of cones decreased rapidly over the time course of the experiment in low-dose and control eyes, reaching 0 by week 24.
What's really interesting is that, in contrast to previous CNTF studies, the research team was able to show that the preserved cones were functional by using behavioural tests and imaging blood flow in the visual cortex.
[...] 'Our results in this mouse model of retinitis pigmentosa clearly show that CNTF treatment can both give life-long protection to cone photoreceptors and preserve useful vision. While there remains a lot to understand, for example on the role of rods in cone preservation and translation to human retinal anatomy, this is a very promising study,” said Robert MacLaren, Professor of Ophthalmology at the Nuffield Laboratory of Ophthalmology.
'We already know from clinical trials aimed at preventing motor neuron loss in ALS that high-dose systemic treatment with CNTF causes too many adverse reactions to be tolerated by patients. However, our results suggest that directly increasing activity in the class of genes that were upregulated in our high-dose CNTF group has the potential to provide a novel, targeted treatment for retinitis pigmentosa and a range of neurodegenerative diseases.'
Pioneering gene therapy takes aim at inherited blindness
(29 June 2015)
EDMONTON — Canada’s first human gene therapy trial for eyes — the replacement of a faulty gene with a healthy one — is now underway at the Royal Alexandra Hospital to preserve and potentially restore vision for people with a genetic disorder that leaves them blind by middle age.
“It’s a great privilege to be able to do something very positive for people with choroideremia,” says clinical research team leader Dr. Ian MacDonald, an ophthalmologist with Alberta Health Services and professor with the Faculty of Medicine & Dentistry at the University of Alberta, sponsor of the research. “People have hoped for this for a long time.”
[...] Dr. MacDonald’s trial involves a new treatment intended to stop choroideremia in its tracks with a single injection of what’s known as a viral vector — a small harmless virus that’s been modified to carry into the eye the ‘good’ gene needed to potentially prevent further loss of sight and to restore the vision of his patients — often with noticeable results in under a month.
[...] The viral vector, known as AAV2-REP1, was provided by NightstaRx Ltd., a private British biopharmaceutical company focused on the development of therapies for retinal dystrophies.
“We are leading the way in the development of an effective gene therapy treatment for choroideremia and this new study, sponsored by the University of Alberta, is another step forward in the development of AAV2-REP1,” says David Fellows, CEO of NightstaRx. “We have been granted Orphan Drug Designation for the product in the United States and Europe and the data to date has shown very promising results.”
The first clinical trials took place at the University of Oxford. Results published in The Lancet Medical Journal in 2014 reported that six months after treatment, the first six patients showed improvement in their vision in dim light; and two of the six were able to read more lines on an eye chart. Oxford research is ongoing under the direction of ophthalmologist Dr. Robert MacLaren.
Research shows possible way to prevent degenerative eye condition
(22 June 2015)
An Oxford University study has found that reducing the tendency of vitamin A to form toxic clumps could slow down a condition that leads to blindness in children and young adults.
[...] To test this theory they used a modified vitamin A, which had deuterium atoms in place of hydrogen at a critical position on the vitamin A molecule. The modified vitamin A was administered in the diet of mice with the Stargardt genetic defect. The incorporation of deuterium atoms on the vitamin prevented it from clumping. As a result, lipofuscin formation was dramatically reduced along with inflammation, and progression of Stargardt disease was prevented. The treatment was also shown to be safe in both mutant and normal mice.
Prof Robert MacLaren, an eye specialist who supervised the project at the Nuffield Laboratory of Ophthalmology added: ‘Stargardt disease affects many children I see in my clinic and ABCA4-related retinal degenerations are also common in adults. The finding that a safe and simple dietary modification may help them is extremely promising. Dr Charbel Issa is to be congratulated for undertaking this incredibly detailed analysis that has provided further scientific validation of inhibiting vitamin A dimerization in this disease. We look forward to the next step of clinical trials.’
MPs support a healthy future for UK medical research
(27 June 2014)
On 16 June, MPs and peers from across Parliament met with biomedical scientists to hear about how their groundbreaking research is helping to tackle conditions such as cancer, dementia, eye disease, Parkinson's, and brain injury in newborn babies.
The reception, organised by the All-Party Parliamentary Group on Medical Research, brought together researchers, patients, parliamentarians and government ministers to discuss how long-term public support and investment can ensure that the UK’s medical research sector continues to make a huge difference to the health and wealth of the nation.
The Wellcome Trust showcased the work of Professor Robert MacLaren and a new gene therapy he’s developing to tackle a form of blindness. Choroideremia is an incurable degenerative disease that causes progressive loss of vision. A multicentre programme to develop and test the safety of a gene therapy treatment for the condition is underway at the University of Oxford, funded through the Health Innovation Challenge Fund - a partnership between the Wellcome Trust and the Department of Health which aims to accelerate the clinical application of innovative research and development.
£12m investment to develop gene therapies for cause of blindness
(30 January 2014)
Nightstar, a new spin-out company from the University of Oxford and its research commercialisation company Isis Innovation, is to receive a £12 million investment from Syncona, an independent subsidiary of the Wellcome Trust.
The company has been formed to develop and commercialise therapies for retinal dystrophies – degenerative conditions that affect vision.
The announcement follows promising results earlier this month from the first clinical trial of a gene therapy for an inherited form of progressive blindness called choroideremia.
The therapy was developed by Professor Robert MacLaren of Oxford University and colleagues, and uses a small modified virus called AAV.REP1 to deliver the correct version of the choroideremia (CHM) gene to cells in the retina of the eye.
The medical journal The Lancet reported that, six months after treatment, the first six patients showed improvement in their vision in dim light and two of the six were able to read more lines on a standard eye chart.
The choroideremia gene therapy will be Nightstar’s first programme of work.
'The £12 million investment in Nightstar represents one of the largest investments in a new academic spin-out in Europe,' said Tom Hockaday, Managing Director of Isis Innovation.
Professor Robert MacLaren of Oxford's Nuffield Laboratory of Ophthalmology said: 'The initial clinical results for choroideremia gene therapy are very promising and they give us an indication of what this technology can achieve in the future.
'The involvement of Syncona through Nightstar will assist the clinical development, including the manufacture of AAV.REP1 to the stringent requirements needed for regulatory approval, which will expedite patients' access to the therapy,' he explained.
Promising first results in gene therapy trial for inherited blindness
(16 January 2014)
Promising results from the first clinical trial of a gene therapy for an inherited cause of progressive blindness called choroideremia are published today in the 'Lancet'. The phase I clinical trial is funded by the Health Innovation Challenge Fund, a partnership between the Wellcome Trust and the Department of Health.
A total of nine patients have now had one eye treated with the gene therapy in operations at the Oxford Eye Hospital, part of the Oxford University Hospitals NHS Trust. The therapy is given in one eye to allow comparison with progression of the disease in the other eye.
Professor Robert MacLaren of the Nuffield Laboratory of Ophthalmology at the University of Oxford, and a consultant surgeon at the Oxford Eye Hospital and honorary consultant at Moorfields Eye Hospital, led the development of the retinal gene therapy and this first clinical trial. He says: "It is still too early to know if the gene therapy treatment will last indefinitely, but we can say that the vision improvements have been maintained for as long as we have been following up the patients, which is two years in one case.
"The results showing improvement in vision in the first six patients confirm that the virus can deliver its DNA payload without causing significant damage to the retina. This has huge implications for anyone with a genetic retinal disease such as age-related macular degeneration or retinitis pigmentosa, because it has for the first time shown that gene therapy can be applied safely before the onset of vision loss."
Gene therapy trial shows promise for type of blindness
(16 January 2014)
The first clinical trial of a gene therapy for an inherited cause of progressive blindness called choroideremia has shown very promising initial results which have surpassed expectations of the Oxford University researchers leading the study.
The aim of the study was to get the gene therapy into the cells in the retina of the eye without causing damage. After six months, however, the patients actually showed improvements in their vision in dim light and two of the six were able to read more lines on the eye chart.
A total of nine patients have now had one eye treated with the gene therapy in operations at the Oxford Eye Hospital, part of the Oxford University Hospitals NHS Trust. The therapy is given in one eye to allow comparison with progression of the disease in the other eye.
The first patient to be treated, Jonathan Wyatt, 65, says: 'My left eye, which had always been the weaker one, was that which was treated as part of this trial...Now when I watch a football match on the TV, if I look at the screen with my left eye alone, it is as if someone has switched on the floodlights. The green of the pitch is brighter, and the numbers on the shirts are much clearer.'
Professor Robert MacLaren of the Nuffield Laboratory of Ophthalmology at the University of Oxford led the development of the retinal gene therapy and this first clinical trial. He says: 'It is still too early to know if the gene therapy treatment will last indefinitely, but we can say that the vision improvements have been maintained for as long as we have been following up the patients, which is two years in one case.'
New stem cell approach for blindness successful in mice
(7 January 2013)
Blind mice can see again, after Oxford University researchers transplanted developing cells into their eyes and found they could re-form the entire light-sensitive layer of the retina.
Videos show the nocturnal mice, which once didn't notice the difference between light and dark at all, now run from the light and prefer to be in the dark – just like mice with normal vision.
The researchers say the approach has relevance for treating patients with retinitis pigmentosa, a condition in which the light-sensing cells in the retina gradually die leading to progressive blindness.
The study was led by Professor Robert MacLaren in the Nuffield Department of Clinical Neurosciences at the University of Oxford, together with Dr Mandeep Singh, an eye surgeon from the National University Hospital of Singapore who is currently undertaking PhD studies in Oxford. The findings are published online in the journal PNAS.
The researchers worked with mice that are blind due to complete loss of the light-sensing photoreceptor cells in their retinas. This is the most relevant mouse model for treating patients who are blind from retinitis pigmentosa.
After two weeks, the researchers showed the cells transplanted into the eye had re-formed a full light-detecting layer on the retina and the mice could see.
The cells used were mouse 'precursor' cells that are on an initial path towards developing into retinal cells.
A pupil constriction test showed that, of the 12 mice that received the cell transplant, 10 showed improved pupil constriction in response to light. This shows that the retinas of the mice were sensing the light once more, and this was being transmitted down the optic nerve to the brain.
Dr Singh says: 'We found that if enough cells are transplanted together, they not only become light sensing but they also regenerate the connections required for meaningful vision.'
Professor MacLaren explains: 'Stem cells have been trialled in patients to replace the pigmented lining of the retina, but this new research shows that the light-sensing layer might also be replaced in a similar way. The light-sensing cells have a highly complex structure and we observed that they can resume function as a layer and restore connections after transplantation into the completely blind retina.'
First blind patient in UK has electronic retina implanted
(3 May 2012)
Chris James has become the first person in the UK to have an electronic retina implanted into the back of his eye.
The operation took place at the Oxford University Hospitals NHS Trust with the surgical team led by Robert MacLaren, Professor of Ophthalmology at the University of Oxford. Professor MacLaren was assisted by Mr Tim Jackson, a consultant ophthalmic surgeon at King's College Hospital in London.
The following week, a second patient – Robin Millar, a 60 year old music producer from London – received a retinal implant at King’s College Hospital, with Professor MacLaren assisting Mr Jackson.
Both patients were able to detect light immediately after the electronic retinas were switched on, and are now beginning to experience some restoration of useful vision. Further operations are now planned for other suitable patients.
The retinal implants have been developed by Retina Implant of Germany to restore some sight to people with retinitis pigmentosa, an inherited condition that affects around one in every 3,000-4,000 people in Europe.
Retinitis pigmentosa is a progressive disease that sees light-detecting cells in the retina deteriorate over time.
Retina Implant’s devices are designed to replace the lost cells in the retina. Patients have a small microchip containing 1,500 tiny electronic light detectors implanted below the retina. The optic nerve is able to pick up electronic signals from the microchip and patients can begin to regain some sight once more.
Professor MacLaren explains: ‘What makes this unique is that all functions of the retina are integrated into the chip. It has 1,500 light sensing diodes and small electrodes that stimulate the overlying nerves to create a pixellated image. Apart from a hearing aid-like device behind the ear, you would not know a patient had one implanted.’
First patient receives novel gene therapy for type of blindness
(27 October 2011)
The first patient to receive gene therapy for an incurable type of blindness was treated at the John Radcliffe Hospital in Oxford this week as part of a trial led by Oxford University.
If successful, the advance could lead to the first-ever treatment for choroideraemia, a progressive form of genetic blindness that first arises in childhood and is estimated to affect over 100,000 people worldwide.
‘This disease has been recognised as an incurable form of blindness since it was first described over a hundred years ago. I cannot describe the excitement in thinking that we have designed a genetic treatment that could potentially stop it in its tracks with one single injection,’ says Professor Robert MacLaren of the University of Oxford, who is leading the trial.
[...] ‘This trial represents the world’s first ever attempt to treat this disease and the first time that gene therapy has been directed towards the light-sensitive photoreceptor cells of the human retina,’ says Professor MacLaren. ‘This represents a major breakthrough and is highly significant for patients who are losing sight from other photoreceptor diseases, such as retinitis pigmentosa.’
The trial will see 12 patients undergo surgery in which the gene therapy is injected into one eye. The other eye would then act as a control against which to assess any treatment effect. The researchers would however aim to go on to treat the second eye, should the treatment be proven to be effective.
The aim of the trial is primarily to assess safety, but it will also gain initial data on how effective the treatment is. The researchers estimate that it will take two years to know whether or not the degeneration has been stopped completely by the gene therapy.
‘While safety appears so far to be fine, the efficacy of the gene therapy will only be evident after 24 months. We need this time to measure any effect as the degeneration caused by choroideraemia is slow,’ explains Professor MacLaren, who is also an honorary consultant at the Oxford Eye Hospital and Moorfields Eye Hospital.