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    Welcome to the UCL EyeTherapy blog

    By Prateek Buch, on 22 June 2012

    Welcome! On this blog you will find:

    Don’t forget to visit our main research website where you will find all the latest information on our work to develop novel treatments for sight loss

    Our latest posts are below – do let us know what you think!

     

     

     

    email: eye.info@ucl.ac.uk        Phone: 0207 608 7982

    International Clinical Trials Day: Our Work in Summary

    By Andi M Skilton, on 20 May 2014

    Gene-cell-therapy-logo-3

    Introduction

    Today, 20 May 2014, is International Clinical Trials Day. This landmark day remembers the pioneering work of James Lind a Scottish naval physician who, in the 1700s, conducted the first controlled clinical study that identified that citrus fruit (containing Vitamin C) was effective in treating scurvy.

    Each year, a number of organisations mark this day with a focus on improving understanding and communication on the importance of controlled clinical trials including the National Institute for Health Research (NIHR) and its NHS partners who are launching their ‘OK to ask’ campaign encouraging patients to ask their doctors about research.

    In support of this day, here at the Gene and Cell Therapy group at UCL Institute of Ophthalmology, we want to highlight our own commitment to improving clinical outcomes for patients with severe vision loss by providing an overview of our on-going clinical trial programme.

    In partnership with the NIHR Moorfields Biomedical Research Centre our clinical trial programme has been running since 2007. We now have two pioneering phase I clinical trials in progress – one treating Leber Congenital Amaurosis Type 2 (LCA2) with gene therapy and the other treating Stargardt Macular Degeneration (SMD) Disease using retinal pigment epithelium (RPE)-derived from embryonic stem cells (ESCs).

    LCA2 and gene therapy

    LCA is an untreatable, inherited eye disorder that affects around 1 in 80,000 people. Shortly after birth patients experience a progressive loss of vision caused by a mutation in at least one of a number of possible genes. For mutations in the gene RPE65 successful studies in animals have shown that gene therapy, which involves injecting a harmless virus containing a normal RPE65 gene into the eye, can restore some aspects of vision.

    This research led to a first-of-its-kind clinical study in humans in 2008 led by Professor Robin Ali, Head of the Department of Genetics, UCL Institute of Ophthalmology. Early results published in the New England Journal of Medicine, show that the experimental treatment appears to be well tolerated and can improve sight.

    SMD and stem cell therapy

    In another first of its kind study in humans, started back in 2012, Professor James Bainbridge, Professor of Retinal studies at UCL Institute of Ophthalmology and Consultant Ophthalmologist at Moorfields Eye Hospital NHS Foundation Trust, has been assisting Advanced Cell Technology (ACT), a US based company, investigate the potential of stem cells for people affected by macular degeneration. SMD is another untreatable condition where onset begins in early childhood (between the ages of six and 12 years). In children with SMD the macula, which is responsible for our central and fine vision, begins to degenerate causing loss of vision that extends into adulthood.

    Participants attend Moorfields regularly for sight assessment and ocular imaging in our pioneering retinal imaging facility. Over the next two years we will continue to collect data to identify any safety concerns and any indication of benefit.

    The future

    These important and innovative trials are only the first step in demonstrating the extent to which gene and cell therapies for inherited eye disease can slow, halt or even reverse severe vision loss. Our early data suggests that these treatments are well tolerated and further studies will be required to show the extent to which they will benefit patients.

    We are committed to ensuring that we continue to be innovators in this field and further clinical studies into other inherited forms of vision loss are planned. Our group has previously shown that gene therapy can restore vision in a mouse model of achromatopsia and in 2013 we were delighted to announce that we had received funding from the Medical Research Council for the development of a gene therapy to treat the most common form of achromatopsia in humans (caused by a mutation in the gene CNGB3).

    Achromatopsia affects 1 in 30,000 people and causes the complete absence of colour vision from birth, a severe reduction in central visual, extreme sensitivity to light and impaired vision in daylight. We are currently seeking the necessary approvals to begin a clinical study in humans and hope to begin recruiting the first patients later this year.

    Closing comments from Professor James Bainbridge

    “We hope that in the future we will be able to extend these technologies to other diseases of the retina. The data we collect from these early clinical trials are already proving invaluable to our research both increasing our understating of how the retina functions and helping us to refine and improve our techniques, the benefits of which we hope to be able to pass onto other clinicians so that they in turn will be able to improve the outcomes for their patients with advanced vision loss.”

    To keep updated with our research please continue to check back on our blog and our website. You can also follow us on Twitter and Facebook and sign up to our annual newsletter. 

    Dr. Adam Dubis: A Researcher With a Vision for Optical Imaging

    By Andi M Skilton, on 16 May 2014

    Adam-Dubis-People-Behind-the-ScienceThis month our own Dr Adam Dubis is profiled as one of the ‘People Behind the Science’. Adam is a Research Associate here at the UCL Institute of Ophthalmology and is the Advanced Human Retinal Imaging Specialist at Moorfields Eye Hospital NHS Foundation Trust. Listen to how Adam got to where he is today and the innovative work he is doing in optical tomography and adaptive optics – which is so essential to our understanding of how potential gene and cell therapies for severe vision loss repair the damage caused by inherited eye disease.

    Prof. Robin Ali sheds light on repairing the retina with stem cells for the ISSCR

    By Andi M Skilton, on 9 May 2014

    Prof Robin AliThis month is Healthy Vision Month and the International Society for Stem Cell Research (ISSCR) are highlighting advancements related to stem cell research and retina repair.

    The ISSCR has invited our own Professor Robin Ali, Head of the Department of Genetics, UCL Institute of Ophthalmology to be an expert contributor on the subject.

    On a webcast yesterday, Thursday 15 May,  Prof Ali discussed the group’s work into photoreceptor transplantation over the last 10 years. The gene and cell therapy group at UCL Institute of Opthalmology has previously demonstrated that precursor rod cells (a type of photoreceptor responsible for night time and dim light vision) when transplanted into mice which can not see in dim light, are able to make the necessary connections to restore night vision.

    The group has now gone on to refine a technique to generate and purify sufficient numbers of embryonic stem cell (ESC)-derived rod cells, at the right stage of development, for transplant into adult mice with degenerated retinas. The process involves generating balls of cells from ESCs called embryoid bodies that organise themselves into structures called optic cups and from which early, rod cells can be harvested. The ultimate goal of this work in mice will be to find ways to develop the technique sufficiently so it can be applied to the production of clinical grade human embryonic stem cells for transplantation.

    There is a good precedent for using stem cell therapy to repair eye damage. Transplanting corneal stem cells to repair chemical burns of the cornea, has been very successful in restoring vision. But the retina – a multi-layered neural network – is a much more complicated structure, so repairing it poses greater challenges.

    A number of different strategies and various types of stem cells are under investigation for the purpose of transplantation. ESCs are best suited for making new retinal cells and data from small, early clinical trials with these cells look promising. However, longer term studies into the tolerability of such transplants are ongoing. It is hoped that in the future there are a number of severe visual impairments that might benefit from such transplants.

    You can watch the full webcast on the ISSCR public channel as well as read the accompanying blog:

    You can also learn more about the research of Prof. Ali and colleagues on our blog and website:

    Registration now open for AMD DAY 2014!

    By Andi M Skilton, on 25 April 2014

    AMD DAY

    We are delighted to announce that we are excepting applications to attend our Age-Related Macular Degeneration Day happening on Saturday July 2014 at the Queen Elizabeth II Conference Centre, Westminster, London.

    This free one-day event provides an opportunity for people with Age-Related Macular Degeneration (AMD) to interact with charities, researchers and healthcare professionals. Patients will hear first-hand the progress being made in world-leading research into gene and stem cell therapies to treat different forms of macular degeneration and be able to discuss the future of our research to ensure it focuses on the aspects of AMD that are most important to people living with AMD.

    The uniqueness of this day is that our patients have set the agenda to ensure our panel of specialists (doctors, scientists, counsellors and nurses) focus on the topics most important to you.

    To register and find out more about AMD Day and our research into AMD please visit our website:

    AMD Day is organised by the Department of Genetics, UCL Institute of Ophthalmology and is funded by the NIHR Moorfields Biomedical Research Centre, a grant from the Wellcome Trust and by the Macular Society.

    UCL Institute of Ophthalmology attends SET for Britain

    By Andi M Skilton, on 21 March 2014

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    SET for Britain logo

    On Monday 17 March, our own Dr Anai Gonzalez-Cordero was one of the hundreds of early-career scientists in Britain invited to Westminster to present their research to Members of both Houses of Parliament (MPs) at SET for Britain.

    Dr Gonzalez-Cordero (one of 60 Biologists and Biomedical scientists in attendance) presented her work on the development of cell therapy techniques to treat vision loss, specifically the transplant of embryonic stem cell (ESC)-derived photoreceptors into the eye to replace those that have lost their normal function.

    Of the day, Dr Gonzalez-Cordero said, “It was a great pleasure to be asked to take part along with so many other talented scientists engaged in really fascinating areas of research. At UCL Institute of Ophthalmology our research into transplanting ESC-derived photoreceptors into the adult diseased retina is still in the early stage of investigation. It was very exciting to have the chance to discuss our work with important decision makers in government and help them to understand why we think these approaches, in the future, may go on to help people with severe vision loss.”

    SET for Britain is an annual event and the result of a collaboration between the Parliamentary and Scientific Committee, Society of Biology, the Royal Academy of Engineering, the Royal Society of Chemistry and the Institute of Physics. It seeks to encourage and support those at the start of their scientific career by providing a forum where scientists can present and discuss their own “ground-breaking and frontier” research with MPs.

    Prof James Bainbridge talks gene therapy for RP with The Naked Scientists

    By Andi M Skilton, on 14 March 2014

    image001In this months podcast from Naked Genetics, entitled DNA Damage and Repair, Prof James Bainbridge, Department of Genetics, UCL Institute of Ophthalmology answers the monthly listener question and provides an update on the current status of research into treating retinitis pigmentosa (an inherited, degenerative eye disease that causes severe vision impairment) with gene therapy.

    Click on the player below to hear Prof Bainbridge’s answer.

    Fun and learning had by all at the BSGCT Public Engagement Day!

    By Andi M Skilton, on 14 March 2014

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    Click on image to enlarge, click back on your browser to return to this blog

    Last week, Fri 7 March, was the public engagement day of the British Society for Gene and Cell Therapy (BSGCT) at the Oxford University Museum of Natural History.

    Dr Tassos Georgiadis, UCL Institute of Ophthalmology has been on the board of the BSGCT since 2012 and chairs the public engagement sub-committee. The day provided the public with an opportunity to hear from a prestigious panel of scientists working at the forefront of gene and stem cell research as well as an opportunity for students to learn more about what it means to be a scientist.

    “The day was a great success and everyone involved has said they really enjoyed it,” said Dr Georgiadis. “We had an eminent speaker panel who were able to talk from their own experiences of working on gene and cell therapies and to dispel many of the myths and misreporting we hear everyday. The audience seemed to really appreciate a chance to learn and hear first-hand why these are such challenging and time intensive treatments to develop.”

    As well as getting to hear about cutting edge research there was the opportunity for attendees to meet, discuss and debate with scientists, patients, journalists and clinicians around the impact that research into genetic and stem cell therapies has for society.

    It was extremely engaging to watch the public as well as GCSE and A-Level students grill the speakers with some highly challenging questions around the technology and ethics behind gene and stem cell therapies. And Adam Pearson, a Patron of Genetic Disorders UK, gave a really enjoyable and honest account of his own experience of living with a genetic condition and the need to ensure that researchers and clinicians keep the person and not the disease at the forefront of their mind.

    Our congratulations go out to everyone involved, for a truly fantastic and inspiring event!

    The Department of Genetics, UCL Institute of Ophthalmology will be holding their own public engagement day on 5 July 2014 for people with age-related macular degeneration (funded by the NIHR BRC Moorfields Eye Hospital NHS Trust, the Macular Society and by a grant from the Wellcome Trust).

    You will have the opportunity to share your experiences of AMD with charities, researchers and healthcare professionals. You will hear first-hand the progress being made in world-leading research into gene and stem cell therapies for AMD and other forms of macular degeneration and have a chance to discuss the focus for future research to enable us to further support the needs and aspirations of people living with AMD.

    Check back at the end of March 2014 for information on how to register to attend.  

    After 50 years, inherited retinal disorders are now the leading cause of blindness in people of working age!

    By Andi M Skilton, on 8 March 2014

    BMJ Open logo

     

     

    Introduction to the paper

    Data published in BMJ Open, from Dr Michel Michaelides, UCL Institute of Ophthalmology, and colleagues show that ‘for the first time in at least five decades, diabetic retinopathy/maculopathy (DRM) is no longer the leading cause of certified blindness among working age adults in England and Wales, having been overtaken by inherited retinal disorders (IRDs)’.

    The authors, from the National Institute of Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Trust and UCL Institute of Ophthalmology, analysed the national database of blindness certificates of vision impairment (CVIs) in England and the Welsh equivalent (CVI-Ws), to determine the number and causes of blindness in people of working age (16 to 64 years, inclusive).

    Findings and speculations from the paper

    The report, A comparison of the causes of blindness certification in England and Wales in working age adults (16-64 year), 1999-2000 with 2009-2010’, reveals that CVIs for IRDs have risen by 4.4% (from 15.8% to 20.2%) moving from second to first position. During the same period CVIs for DRM have decreased, dropping 3.3% (from 17.7% to 14.4%), whilst optic atrophy remains the third leading cause.

    “What is clear from the findings is that inherited retinal disease should no longer be thought of as rare and not relevant,” says Dr Michaelides. “These conditions have long been, and will continue to be, an important avenue of our research. But in the future the provision of care and resources in the NHS and the allocation of research funding must be addressed if we are to tackle these conditions which now represent the commonest cause of certification in the working age population.”

    The authors speculate that it is perhaps the allocation of resources and funding seen in recent years for diabetes that has led to a subsequent decrease in CVIs for DRM. This decline is not an indication that incidence of diabetes (and subsequently incidence of DRM) are decreasing as latest data shows an increase. Likewise, incidences of IRD are not necessarily rising. Instead these findings could be attributed to the increased focus of the Government and Health Services in recent years on the treatment and management of diabetes and the effectiveness of DRM screening programmes and strategies to improve glycaemic control, among others.

    Implications of the findings from the paper

    This analysis takes into consideration only those cases which have been certified. Certification in England and Wales is by no means compulsory and many cases of vision loss go undiagnosed, misdiagnosed or unreported. However, these findings formalise the diagnostic trends that RP Fighting Blindness, a national charity funding pioneering research and support services for people with Retinitis Pigmentosa and other related conditions, have been noticing for some years.

    Whilst in terms of absolute numbers other conditions that cause severe vision loss such as age-related macular degeneration affect more people, the national impact of IRDs on the productivity of this otherwise fit and able group of working age people, as well as additional health and social costs, is huge. This is why a new focus on IRDs supported by the learnings from other diseases such as diabetes will be so important for the future.

    Taking a glimpse at our work in AMD

    By Andi M Skilton, on 28 February 2014

    As February is Age-Related Macular Degeneration (AMD) month we thought this would be an opportune moment to highlight some of the ongoing AMD research within the Gene and Cell Therapy group at the Department of Genetics at UCL Institute of Ophthalmology, as well as announce an upcoming opportunity to be more involved in shaping the future of our research.

    What is AMD?

    AMD is one of the leading causes of vision loss amongst those over the age of 50 and is caused by damage to the macula, the part of the eye responsible for central vision. Whilst vision loss isn’t total, many people with AMD are unable to see detail. As the disease progresses some people find that straight lines become distorted and the central vision of one or both eyes becomes blurred making it difficult to recognise faces, read or watch TV.

    If you or someone you know has been diagnosed with AMD your doctor is likely to have classified your condition as being one of two forms:

    • “dry” AMD – characterised by the loss of retinal pigment epithelium (RPE), the cells that nourish the light-sensitive photoreceptors found in the macular.
    • “wet” AMD – occurring in approximately 10 to 15% of people with AMD and caused by the abnormal growth of blood vessels from the choroid into the retina (a process called choroidal neovascularisation [CNV]). These new blood vessels are fragile and can leak blood behind the macula, rapidly damaging light-sensitive cells and causing sight loss.
    Diagram of the eye

    Click image to enlarge, click back on your browser to return to the blog

    There is no treatment for dry AMD. Existing therapies (including laser treatments, surgery and anti-VEGF injections) can delay disease progression in the wet form. These treatments do not work for everyone and can result in harmful side effects. This is why ongoing research is so important to improve the future of treatment for this major cause of sight loss.

    AMD is a multifaceted disease

    AMD has been a focus of our research for a number of years. We want to understand the pathology and biological pathways involved in AMD with the aim of identifying possible future treatment targets. Dr Ulrich Luhmann, a Senior Research Associate at the Institute, is one of several members of our team focusing on AMD.

    Dr Luhmann explains – we often think of AMD as being one disease with a wet and a dry form but the situation is much more complex. The role of VEGF in wet AMD (and other diseases) is well understood and as such it has become an established target to treat symptoms. However, there are other pathways that are responsible for AMD but the roles of these are less well understood.

    We now know that AMD is a group of disorders associated with the innate immune response, one of the bodies first defence mechanisms against infection and damage. A number of genetic factors increase our risk of developing AMD, their effect can become more pronounced as we age and in some cases further affected by external influences like smoking and diet. The aim of our research is to understand how these risk factors define a persons’ actual risk of developing AMD in order to identify novel targets for novel therapeutic strategies.

    Diagram showing the factors that define a persons risk of developing AMD

    Click image to enlarge, click back on your browser to return to the blog

    Possible future treatment strategies for AMD

    Gene and stem cell therapies are just two of the strategies under investigation here at the Department of Genetics at UCL Institute of Ophthalmology. As we learn more about how the various risk factors for AMD affect one another we hope to use this information to develop potential new treatments to prevent or reverse vision loss in AMD and other forms of macular degeneration.

    Diagram of our research approach for AMD

    Click image to enlarge, click back on your browser to return to the blog

    One such approach is gene therapy. In the future it may be possible for us to use gene therapy to target genes within the cells affected by macular degeneration and alter them to promote normal function. We are also looking at the possibility of introducing genes that encode helpful biological molecules like growth factors and antibodies. These genes would sit outside the cells where the products they encode could be produced at a higher than normal quantity to encourage normal cell function and growth or drive the removal of harmful, damaging substances from the eye.

    We are already conducting very early studies into gene therapy to treat a rare retinal disorder called Leber Congenital Amaurosis (LCA). More information on the LCA trial can be found on our website.

    For people who have sustained severe damage to the tissues of the eye, healthy cells derived from stem cells in the laboratory might be useful to replace tissues which are damaged beyond repair. Early studies into the safety of such a procedure are underway for a specific inherited form of macular degeneration called Stargardt’s disease. More information on the Stargardts trial can be found on our website.

    Our research into AMD is ongoing and we hope that our early work into gene and stem cell therapies in other diseases will help develop treatments for people with AMD in the future. More information on our work into AMD can be found on our website.

    How you can help shape the future of our AMD research

    Following on from our extremely successful Retina Patient Day in 2012 we are delighted to announce that we have received funding from The Wellcome Trust to run a similar event for people with AMD.

    On 5 July 2014 in London, UK we are running a free one-day event, endorsed by the UK Macular Society, to provide an opportunity for people with AMD to interact with charities, researchers and healthcare professionals. This is an opportunity to hear first-hand the progress being made in our world-leading research into AMD and to share your personal experiences and insights of living with this condition. With your input we will be able to ensure that our research focuses on the aspects of AMD that are most important to you.

    New Breakthrough: transplantation of photoreceptors from retina grown ‘in a dish’

    By Prateek Buch, on 22 July 2013

    Cover of Nature Biotechnology journal featuring our latest stem cell breakthroughThe UCL gene and cell therapy group, led by Professor Robin Ali, have carried out the first successful transplant of light-sensitive photoreceptor cells taken from a synthetic retina, grown ‘in a dish’ from embryonic stem cells.

    When transplanted into night-blind mice these cells appeared to develop normally, integrating into the existing retina and forming the nerve connections needed to transmit visual information to the brain.

    The findings, published today in Nature Biotechnology, suggest that embryonic stem cells could in future provide a potentially unlimited supply of healthy photoreceptors for retinal cell transplants to treat blindness in humans.

    The loss of photoreceptors – light sensitive nerve cells that line the back of the eye – is a leading cause of sight loss in degenerative eye diseases such as age-related macular degeneration, retinitis pigmentosa and diabetes-related blindness.

    There are two types of photoreceptor in the eye – rods and cones. Rod cells are especially important for seeing in the dark as they are extremely sensitive to even low levels of light.

    Previous work by our team at UCL (University College London) Institute of Ophthalmology and Moorfields Eye Hospital has shown that transplanting immature rod cells from the retinas of healthy mice into blind mice can restore their sight. However, in humans this type of therapy would not be practical for the thousands of patients in need of treatment.

    Using a new laboratory technique involving 3D culture and differentiation of mouse embryonic stem cells, which was developed recently in Japan, we were able to grow retinas containing all the different nerve cells needed for sight.

    Commenting on the latest breakthrough, Professor Ali said:

    “Over recent years scientists have become pretty good at working with stem cells and coaxing them to develop into different types of adult cells and tissues. But until recently the complex structure of the retina has proved difficult to reproduce in the lab. This is probably because the type of cell culture we were using was not able to recreate the developmental process that would happen in a normal embryo.

    “The new 3D technique more closely mimics normal development, which means we are able to pick out and purify the cells at precisely the right stage to ensure successful transplantation. The next step will be to refine this technique using human cells to enable us to start clinical trials.”

    We grew retinal precursor cells using the new 3D culture method and compared them closely with cells developed normally, looking for different markers at different stages of development. We also carried out tests to look at the genes being expressed by the two types of cells to make sure they were biologically equivalent.

    We then transplanted around 200,000 of the artificially grown cells by injecting them into the retina of night blind mice. Three weeks after transplantation the cells had moved and integrated into the recipient mouse retina and were beginning to look like normal mature rod cells. These cells were still present six weeks after transplantation. We also saw nerve connections (synapses), suggesting that the transplanted cells were able to connect with the existing retinal circuitry.

    Dr Rob Buckle, Head of Regenerative Medicine at the MRC, said:

    “Regenerative medicine holds a great deal of promise for treating degenerative diseases and the eye is one area in particular where scientists are making very rapid progress. This study is an important milestone on the road to developing a widely available cell therapy for blindness as it identifies critical steps needed to improve the success of cell transplantation and proves unequivocally that embryonic stem cells can provide a renewable source of photoreceptors that could be used to treat blindness.”

    See news items on this research:

     

    BBC: ‘Big leap’ towards curing blindness in stem cell study

    Independent: Cells to restore eyesight are grown in lab and transplanted into blind mice

    Daily Mail: Could cell transplant give sight to millions? Scientists grow retinas in the lab to create crucial connections to the brain

    Guardian:Embryonic stem cells could help restore sight to blind

    New Scientist:Eye receptor transplant promises therapy for blindness