Gene therapy shows promise in tackling common cause of childhood blindness
(26 February 2020)
X-linked retinitis pigmentosa, caused by mutations in RPGR gene, is the most common cause of blindness in young people. The inherited mutations lead to degeneration of light sensitive cells (photoreceptors) beginning in early childhood leading to severe sight loss.
Until now there has been no treatment for this disease. Gene therapy using viral vectors to deliver a healthy copy of a mutated gene into affected cells aims to slow down the degeneration and preserve visual function.
[...] Eighteen patients in total were treated with increasing doses of the vector carrying an RPGR gene in which the DNA had been altered, but in a manner that still allowed correct production of the missing protein.
[...] Professor MacLaren, Consultant Ophthalmologist at the Oxford Eye Hospital, commented: 'We are delighted with the early results of this clinical trial for a degenerative eye disease. It is becoming more apparent to us that novel genetic therapies, when working, lead to a clear improvement in neuronal function, which holds great hope for a variety of other degenerative conditions that have a genetic basis.
'Once again, we should take note that this highly successful international gene therapy clinical trial originated in the NHS by applying science that was previously developed in a project funded in the UK by the Medical Research Council.'
First patients begin gene therapy treatment for blindness as part of NHS Long Term Plan
(17 February 2020)
The first patients have received a revolutionary new gene therapy that can restore eyesight as part of the NHS Long Term Plan.
Babies born with an inherited retinal disorder, known as Leber’s Congenital Amaurosis (LCA), have poor sight which swiftly deteriorates, with many ultimately losing their vision completely in childhood.
The life-changing treatment for children and adults – voretigene neparvovec – is the first in a new generation of gene therapies that can be directly administered to patients, in this case through an injection. Many patients in the trials recovered their night time vision with this treatment.
[...] Robert MacLaren, Consultant Ophthalmologist at Oxford University Hospitals, said: “I am delighted to see that gene therapy research has finally come to fruition and we now have our first approved treatment – in this case for a rare form of genetic blindness.
“The NHS has been leading the world in gene therapy research with several successful clinical trials.
“The recent decision by NICE to provide this novel treatment for our patients shows how the UK is maintaining its global position in delivering first class healthcare.”
World’s first gene therapy operation for common cause of sight loss carried out
(19 February 2019)
Researchers in Oxford have carried out the world’s first gene therapy operation to tackle the root cause of age-related macular degeneration (AMD), the UK’s most common cause of sight loss.
The procedure was carried out at the John Radcliffe Hospital by Professor Robert MacLaren, Professor of Ophthalmology at the University of Oxford, with the support of the NIHR Oxford Biomedical Research Centre in a clinical trial sponsored by Gyroscope Therapeutics, a UK-based company developing genetically-defined therapies for the treatment of eye diseases.
Professor MacLaren says: 'AMD is the number one cause of untreatable blindness in the developed world. A genetic treatment administered early on to preserve the vision in patients who would otherwise lose their sight would be a tremendous breakthrough and certainly something I hope to see in the near future.'
[...] The operation involves detaching the retina and injecting a solution containing a virus underneath. The virus contains a modified DNA sequence, which infects cells, called the retinal pigment epithelium (RPE), and corrects a genetic defect that causes AMD. Ideally if successful, gene therapy would only need to be performed once, as the effects are thought to be long-lasting.
[...] Professor MacLaren said: 'This is a rapidly evolving field. Given that we understand a lot more now about the manufacture of the treatment, and the effects of the virus when doing gene therapy at the back of the eye, as well as all the other gene therapy programmes being developed at the moment, I would hope that we’ll see a treatment for people with dry AMD within the next few years.'
World’s first gene therapy operation for common cause of sight loss carried out
(19 February 2019)
NIHR researchers have carried out the world’s first gene therapy operation to treat age-related macular degeneration (AMD), the most common cause of sight loss in the UK.
The procedure was carried out by Professor Robert MacLaren, Professor of Ophthalmology at the University of Oxford, with support from the NIHR Oxford Biomedical Research Centre in a clinical trial sponsored by Gyroscope Therapeutics.
AMD affects over 600,000 people in the UK. The ‘dry’ form of the disease causes a slow deterioration of the cells of the macula, affecting the central part of a patient’s vision with gaps or ‘smudges’ and making everyday activities like reading and recognising faces difficult.
The operation involves detaching the retina and injecting a solution containing a virus underneath. The virus contains a modified DNA sequence, which infects cells and corrects a genetic defect that causes AMD.
The aim of the therapy is to halt the progress of the condition and preserve what vision patients have remaining. If successful, it is hoped that gene therapy can be used in the future on patients with early AMD and so halt the disease before their vision has started to deteriorate.
Prof MacLaren says: “A genetic treatment administered early on to preserve the vision in patients who would otherwise lose their sight would be a tremendous breakthrough and certainly something I hope to see in the near future.”
Gene therapy breakthrough in treating rare form of blindness
(9 October 2018)
Positive results of the world’s first gene therapy trial for a genetic cause of blindness known as choroideremia have been reported in Nature Medicine.
The trial involved 14 patients receiving a single injection into the back of the eye of a virus containing the missing gene and began in 2011 at the Oxford Eye Hospital - part of the Oxford University Hospitals NHS Foundation Trust. By the end of the study there was a significant gain in vision across the group of patients as a whole.
Furthermore, of the 12 patients who received the treatment without any complications, 100% either gained or maintained vision in their treated eyes, which was sustained for up to 5 years at the last follow up. During this time only 25% of the untreated eyes which acted as controls maintained vision. The gene therapy treatment was generally well tolerated and there were no significant safety concerns.
Professor Robert MacLaren the ophthalmologist who led the trial said: 'The early results of vision improvement we saw have been sustained for as long as we have been following up these patients and in several the gene therapy injection was over 5 years ago. The trial has made a big difference to their lives.'
The success of the Oxford study has since led to a much larger international gene therapy trial involving over 100 patients across nine countries in the EU and in North America. It is now led by Nightstar Therapeutics, a gene therapy spin-out company established by the University of Oxford and Syncona to develop the treatment further. If successful the follow on trial could result in the gene therapy treatment being formally approved by the relevant regulatory bodies worldwide.
Gene therapy breakthrough in treating a rare form of blindness
(8 October 2018)
Researchers have successfully used gene therapy to improve the vision in people with a rare genetic cause of blindness, in the world’s first gene therapy trial for choroideremia.
Gene therapy alters or corrects inherited diseases at the level of the DNA. If successful, a single treatment might have life-long effects.
Choroideremia is an incurable disease caused by a defect in the CHM gene that causes progressive blindness in men.
This new trial involved giving 14 patients at Oxford University Hospitals NHS Foundation Trust a single injection into the back of the eye to deliver a healthy copy of the CHM gene to affected cells in the retina. By the end of the study there was a significant gain in vision across the group of patients as a whole.
Of the 12 patients who received the treatment without any complications, 100% either gained or maintained vision in their treated eyes. This improvement was sustained for up to 5 years at the last follow up. During this time only 25% of the untreated eyes that acted as controls maintained vision.
Professor Robert MacLaren, the ophthalmologist who led the trial, said: “The early results of vision improvement we saw have been sustained for as long as we have been following up these patients and in several the gene therapy injection was over 5 years ago. The trial has made a big difference to their lives.”
First U.S. Patient Treated with Nightstar Gene Therapy for X-Linked Retinitis Pigmentosa
(05 October 2018)
A Puerto Rican patient with X-linked retinitis pigmentosa (XLRP) is hoping to save his vision after an innovative gene therapy procedure at Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine. On August 23, Julio Adorno Nieves, 23, became the first U.S. patient to receive new genes for his inherited, blinding condition in a worldwide Nightstar Therapeutics clinical trial.
[…] Byron Lam, M.D., professor of ophthalmology and holder of the Robert Z. and Nancy J. Greene Chair in Ophthalmology, said XLRP is most commonly caused by a mutation on the RPGR gene on the X chromosome, which causes blindness in about 1 in 15,000 men. Women are usually less affected because they have two X chromosomes, but they can pass the mutation on to their children.
“Introducing a functional copy of the RPGR gene using an engineered viral vector can correct the underlying cause and induce a long-lasting therapeutic effect,” said Dr. Lam, the principal investigator in the phase 1/II Nightstar clinical trial focusing on the safety and dosage of the treatment.
Janet L. Davis, M.D., professor of ophthalmology and holder of the Leach Chair in Ophthalmology, and Ninel Gregori, M.D., associate professor of clinical ophthalmology, delivered the new genes to Nieves’ left eye in a 99-minute procedure. The surgery was observed by Robert MacLaren, M.D., a professor of ophthalmology at the University of Oxford in the United Kingdom, who developed the gene-replacement therapy.
First human test of robotic eye surgery a success
(18 June 2018)
Researchers from the University of Oxford have completed the first successful trial of robot-assisted retinal surgery.
The trial, supported by the National Institute for Health Research Oxford Biomedical Research Centre, took place at Oxford’s John Radcliffe Hospital. It involved 12 patients and is published this week in Nature Biomedical Engineering.
Half were randomly allocated robot-assisted surgery and the other half to standard manual surgery to remove a membrane from the back of the eye. Using the robot, the surgeon was able to perform the procedure with equal or better efficacy than in the traditional manual approach. In the second phase of the trial, the team used the robot to insert a fine needle under the retina to dissolve blood in three patients who had age-related macular degeneration. All experienced an improvement in their vision as a result.
Robert MacLaren, Professor of Ophthalmology at the University of Oxford, said: ‘This is a huge leap forward for delicate and technically difficult surgery, which in time should significantly improve the quality and safety of this kind of operation. The trial also showed that the robot has great potential for extending the boundaries of what we can currently achieve.
‘Our next step will be to use the robotic surgical device for precise and minimally traumatic delivery of a gene therapy to the retina, which will be another first-in-man achievement and is set to commence in early 2019.’
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.
[...] 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.
Retinitis pigmentosa is currently untreatable and leads to a slow and irreversible loss of vision.
The trial is being run by Nightstarx Ltd (Nightstar), a biopharmaceutical spinout company of Oxford developing gene therapies for inherited retinal diseases, and researchers from the University of Oxford. On 16 March 2017, a 29 year old British man became the first patient with X-linked retinitis pigmentosa to undergo gene therapy. The operation took place at the Oxford Eye Hospital, part of the Oxford University Hospitals NHS Foundation Trust.
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.
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.
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.
[...] 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 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.'
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.
[...] Surgeons at the Oxford Eye Hospital at Oxford's John Radcliffe Hospital implanted a tiny electronic chip at the back of Rhian's retina in her right eye as part of ongoing NHS-funded research of the technology.
[...] 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.'
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.
Founding investor Syncona, an independent subsidiary of the Wellcome Trust, also contributed to the funding. Nightstar has also expanded its pipeline with 5 further programme licences from the University of Oxford through its technology commercialisation subsidiary,Oxford University Innovation. The funds will enable Nightstar to continue clinical development of its gene therapy for choroideremia and advance multiple retinal gene therapy programs into human trials.
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 gives long-term protection to photoreceptor cells in a mouse model of retinitis pigmentosa
(15 July 2015)
A collaboration between scientists in the UK and the USA has shown that gene therapy can give life-long protection to the light-sensitive photoreceptor cells responsible for colour vision in a mouse model of the most common inherited eye disorder.
Results published in the journal Molecular Therapy demonstrate that the preserved cells were able to drive visually-guided behaviour, even in later stages of the condition and despite becoming less sensitive to light.
These findings are significant because they open up a new line of research to prevent nerve cell death in retinitis pigmentosa and age-related macular degeneration. They may also have a wider application to neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS).
[...] 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.
[...] '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.
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.
People usually associate vitamin A as being good for the eyes, but the study found that in patients with Stargardt disease, vitamin A transforms into toxic compounds, which cause chronic inflammation, premature ageing of the retina and vision loss.
[...] 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.
[...] 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.
The aim of the treatment in this 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.
[...] 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.
[...] 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.
[...] 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.'
[...] 'We have shown the transplanted cells survive, they become light-sensitive, and they connect and reform the wiring to the rest of the retina to restore vision,' he says. 'The ability to reconstruct the entire light sensitive layer of the retina using cell transplantation is the ultimate goal of the stem cell treatments for blindness we are all working towards.'
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 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.
[...] 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.’
[...] After having the artificial retina implanted in his left eye, Chris can now recognise a plate on a table and other basic shapes. And his vision is continuing to improve as he learns to use the electronic chip in an eye that has been completely blind for over a decade.
[...] Professor MacLaren says: ‘We are all delighted with these initial results. The vision is different to normal ... and it requires a different type of brain processing. We hope, however, that the electronic chips will provide independence for many people who are blind from retinitis pigmentosa.’
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 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.