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UCL EyeTherapy Blog


A blog by the Gene and Cell Therapy Group at the UCL Institute of Ophthalmology Department of Genetics


Archive for the 'News' Category

Athena Vision launches; developing gene therapies for devastating eye diseases

Andi MSkilton24 November 2015

Athena Vision logo

Athena Vision is focused on developing gene therapies for eye diseases based on research conducted at UCL

Today sees the launch of Athena Vision Limited a biopharmaceutical company focused on the development of gene therapies to treat a range of devastating eye diseases causing blindness.

Launched by UCL Business PLC, the wholly-owned technology transfer company of UCL, Athena has entered into a global partnership with MeiraGTx Limited to develop and commercialise Athena’s ocular gene therapy programmes arising from research conducted by Professor Robin Ali, Head of the Department of Genetics at the UCL Institute of Ophthalmology and a leader in the field of cell and gene therapy for the eye.

MeiraGTx, which is developing gene therapies for ocular diseases, neurodegenerative disorders and other diseases, will advance Athena’s pipeline of gene therapies through clinical trials to commercialisation. The partnership will pursue four initial clinical programmes in inherited retinal conditions: Leber congenital amaurosis type 2 (LCA2) caused by deficiencies in RPE65, achromatopsia caused by mutations in CNGB3 or CNGA3 and X-linked retinitis pigmentosa caused by mutations in RPGR. A Phase I/II dose-escalation clinical trial in LCA2 is expected to start in 1Q 2016. Development costs for all four programmes are supported by an undisclosed upfront payment by MeiraGTx.

Athena and MeiraGTx have unparalleled access to resources through their affiliation with the UCL Institute of Ophthalmology and its partner Moorfields Eye Hospital, which together form one of the world’s largest vision research centres, with access to a sizable and diverse patient population. The National Institute for Health Research (NIHR) Moorfields Biomedical Research Centre and Clinical Research Facility will support the translation of the partnership’s gene therapy programs from the laboratory to early-phase clinical testing.

The establishment of Athena accelerates the development of promising new therapies for inherited retinal diseases, which have been supported by the Medical Research Council (MRC), from early-stage research through clinical development via the MRC’s Developmental Pathway Funding Scheme (DPFS).

“With MeiraGTx, we have the necessary technology and critical mass to deliver a pipeline of novel therapeutics to change patients’ lives,” said Professor Ali, UCL Institute of Ophthalmology and Principal Founder, Athena.

“Athena’s leadership has expertise in developing advanced therapeutics from inception through clinical application. With MeiraGTx, we are building an integrated, global gene therapy business that brings together therapeutic and platform-based technologies along with extensive clinical, manufacturing and commercial experience,” said Stuart Naylor, CEO, Athena.

“This new rapid translation of world-leading science into clinical application and large inward investment to the UK highlights the importance of continued governmental support for scientific research,” said Professor Sir Peng Tee Khaw, Director of the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology.

“We are delighted with such substantial investment to advance novel gene-based therapies. With the formation of this partnership, UK biomedical science continues to demonstrate its importance in the world sphere and, with sustained external and government support, our biomedical research leaders have true potential to bring to fruition innovations in treatment to benefit patients globally,” said Professor Philip J Luthert, Director, UCL Institute of Ophthalmology.

“The formation of Athena and the significant partnership with MeiraGTx provides a clear route for the translation and commercialisation of the world-class research strengths of Professor Robin Ali and his team at the UCL Institute of Ophthalmology. We look forward to supporting Athena as it commences its important work to deliver novel treatments to benefit patients with vision loss across the world,” said Cengiz Tarhan, Managing Director of UCLB.

UCL RPE65 Gene Therapy Trial Shows Benefit in People with Leber Congenital Amaurosis Type 2 for up to Three Years After Treatment

Andi MSkilton5 May 2015

NEJM 2015 Cover

We are delighted to be able to announce that yesterday, Monday 4th May, the long-term results of our RPE65 gene therapy trial for Leber Congenital Amaurosis Type 2 (LCA2) were published in the prestigious New England Journal of Medicine.

Begun in 2007, this was the world’s first-in-human trial of gene therapy to treat an inherited form of blindness. Twelve patients were enrolled in the trial over the course of six years and followed up over a three year period to assess the long-term safety and benefit of treatment with gene therapy in this Phase I/II clinical trial.

A number of patients enrolled in the trial experienced gains in night vision for a period of two to three years with greatest improvements seen in the first 6 to 12 months after treatment. This is consistent with the published results and interim findings of other studies of RPE65 gene therapy.

This study confirms our preliminary findings (published in NEJM, 2008) that gene therapy can improve night vision, providing further evidence of benefit in inherited blindness.
Professor James Bainbridge, lead clinician for the trial

Our latest results provide confirmation of efficacy but the data, together with results of a parallel study in dogs, indicate that the demand for RPE65 is not fully met with the current generation of vectors. We have concluded that early intervention using a more potent vector, expressing higher levels of RPE65 is likely to provide greater benefit and protection against progressive degeneration.
Professor Robin Ali, lead for the research group

The group has now developed a new, more powerful gene therapy vector and is aiming to test this in a second clinical trial funded by The UK Medical Research Council.

Links to further information:

  • The full results from this study can be found in the NEJM:
  1. Bainbridge, JWB, Mehat MS, Sundaram V, et al. Long-term Effect of Gene Therapy on Leber Congenital Amaurosis. New England Journal of Medicine. 2015;10.1056/NEJMoa1414221
  2. Bainbridge, JWB, Smith AJ, Barker SS, et al. Effect of Gene Therapy on Visual Function in Leber’s Congenital Amaurosis. New England Journal of Medicine. 2008; 358: 2231-9

UCL Researchers Solve a Major Riddle of Retinal Degeneration Research for Retinitis Pigmentosa!

Andi MSkilton26 January 2015

Today a paper published in Nature Communications from the Gene and Cell Therapy Group at the UCL Institute of Ophthalmology has shed light on why, until now, it has not been possible to effectively restore vision in rd1 mice – the world’s major model for retinitis pigmentosa (RP).

rd1 mice retina at 13 weeks of age and after treatment with PDE6B gene therapy in the first month of life

Seen at 13 weeks of age, PDE6B gene therapy given to rd1 mice in the first month of life preserves rod cells in the retina (Panel 1: ‘normal’ mouse retina – untreated; Panel 2: rd1 mouse retina – untreated; Panel 3: rd1 mouse retina – treated with PDE6B gene therapy)

The rd1 mouse is a model of retinitis pigmentosa caused by defects in the PDE6B gene. The model was first described back in 1924 and is the oldest and most widely used model of retinal degeneration in the world. When light enters the eye and hits the rod cells (a type of photoreceptor – the light sensing cells of the eye), PDE6B is required to help turn this stimulus into electrical signals that can be understood by the brain and translated into an image. In rd1 mice, the defect in PDE6B leads to a rapid degeneration of the retina within the first four weeks of life, which is characterised by the death of rod cells and a complete loss of vision.

Numerous attempts have been made to preserve and restore function to rod cells in rd1 mice in the hope that an approach towards developing a treatment for RP patients could be identified. Past attempts to restore vision in these mice using gene therapy (where the normal gene is put back into the effected cells by means of a harmless virus known as a vector) has had limited success. In this model retinal degeneration happens appears to happen so quickly that there aren’t enough, if any, healthy rod cells left to treat.

In other animal models (such as dogs) where progression of retinal degeneration caused by defects in PDE6B is somewhat slower, a restoration of vision has been possible and has led to the conclusion that in rd1 mice the degeneration happens too quickly to allow for a window of opportunity to treat. This has confused the issue around whether a gene therapy approach to treating this form of RP in people could be effective.

Recent work from our group in other more severe forms of retinal degeneration, specifically that of Leber Congenital Amaurosis Type 4 (LCA4 [caused by a defect in the gene AIPL1]), however, has cast doubts on this explanation of previous findings in rd1 mice. Using an AIPL1 gene therapy we have been able to rescue vision loss in an LCA4 mouse model, which experiences a complete loss of vision in the first three weeks of life; faster than in rd1 mice.

Using the latest in gene therapy vector technology, the team has successfully created a more efficient and rapid acting PDE6B gene therapy then had previously been possible to address the short window of opportunity to treat. This approach was able to not only preserve the rod cells but restore their function as well (see picture above). However, despite this, the team found that these mice were still not responding to a light stimulus suggesting that somewhere in the pathway that carries signals from the rod cells to the brain there must be a second and currently unreported defect blocking the signal.

An analysis of the genetic code of rd1 mice has indeed identified a defect in a gene called GPR179 that had not previously been found in the rd1 mouse strain, but has been previously reported in other mouse strains. This defect affects the retinal bipolar cells – specialised cells that help transmit signals from the photoreceptors of the eye to the nerve cells that carry signals up to the brain. This defect is likely to be found in most of the rd1 mice around the world today and could have been present in this mouse strain for as long as 65 years. Through a process of selective breeding of different mouse models the team have successfully removed the GPR179 defect from rd1 mice and been able to demonstrate that PDE6B gene therapy does indeed lead to the preservation and restoration of rod cell function and that these mice can still sense and respond to light a year after treatment.

This study provides strong evidence to support the potential of gene therapy for RP caused by defects in the PDE6B gene and future studies will be required to assess further the potential. This study by no means suggests that previous work in rd1 mice is not valid but instead highlights the need, where appropriate, to reassess past findings and ensure that future work considers if the presence of a GPR179 defect may be a contributing factor to the results.

Professor Ali Honoured for his Contribution to Research into Retinal Disease

Andi MSkilton8 September 2014

Prof Robin Ali








Professor Robin Ali, PhD, Professor of Human Molecular Genetics and Head of the Department of Genetics, UCL Institute of Opthalmology has been awarded the Pioneer Award for his work in proof-of-concept studies that have demonstrated the feasibility of using gene therapy and cell transplantation to treat dysfunction and degeneration of the cells of the retina as well as his work on the first clinical trial for inherited retinal degeneration.

The award is presented by the journal of Human Gene Therapy (the official journal of the European Society of Gene and Cell Therapy and British Society for Gene and Cell Therapy, among others) who are commemorating their 25th anniversary by recognising leadership and contributions to the field of gene therapy to treat retinal degeneration leading to blindness. Professor Ali is joined by co-recipiants Jean Bennett, MD, PhD, Perelman School of Medicine, University of Pennsylvania, and William Hauswirth, PhD, University of Florida College of Medicine.

Achromatopsia Might not be as Progressive as Previously Thought

Andi MSkilton8 September 2014

A recent publication from the UCL Institute of Ophthalmology, Moorfields Eye Hospital, and the Medical College of Wisconsin indicates that for the majority of people with achromatopsia, the condition may not be as progressive as previously suggested.

Data from this study by Aboshiha et al. demonstrated that for the majority of people with achromatopsia (a rare, inherited genetic disease of the eye) vision and the structure of the retina (the light-sensitive layer at the back of the eye) doesn’t worsen over time, and in the small number of people where it does, these changes in vision are slow and unrelated to a person’s age or to the genetic cause of their condition.

Published in the journal of Investigative Ophthalmology and Visual Science, this UK and US collaboration is the largest and longest follow up of patients with achromatopsia published to date with 38 people (20 men and 18 women, aged between 6 and 52) with genetically confirmed achromatopsia assessed for progression over an average of approximately two years.

Until fairly recently achromatopsia was described as being stationary i.e. that it did not change over time. However, a number of recently published studies using new retinal imaging techniques have suggested a possible worsening of achromatopsia as people age. Nearly all previous studies have been small cross-sectional studies (i.e. a range of different people were monitored and data collected at a set point in time) where as this study is longitudinal (i.e. we have monitored a range of different people but collected data over a period of time), which has helped to clarify the role of progression in achromatopsia.

Prof Michel Michaelides, Professor of Ophthalmology at the UCL Institute of Ophthalmology and Consultant Ophthalmologist at Moorfields, lead the study –

“In conditions where there is progressive worsening as people get older we often need to treat as early as possible to see a benefit. Currently there are no treatments for achromatopsia but due to promising results reported for gene therapy studies in animals, there are plans for human clinical trials in the near future. The data from this study indicates that because progression of achromatopsia is indeed quite minimal more people may be able to benefit from treatments in the future then we previously thought.”

Achromatopsia causes the dysfunction of the light sensitive cone cells in the eye in approximately 1 in 30,000 people and is characterised by involuntary and repetitive movement of the eyes (nystagmus), poor clarity of vision (visual acuity) and sensitivity to light (photophobia). People with achromatopsia have mutations in one of five genes important for vision: CNGA3 and CNGB3, which account for 70% of all cases, as well as GNAT2, PDE6C and PED6H.

In 2013 the UCL Institute of Ophthalmology received a £2.1 million grant from the Medical Research Council to conduct an early phase I/II gene therapy clinical trial over the next five years in people with achromatopsia caused by defects in the CNGB3 gene. The clinical trial will assess if adding normal CNGB3 into the cells of the eye is safe and has any potential benefit for vision.

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

Andi MSkilton16 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 James Bainbridge Talks Gene Therapy for Retinitis Pigmentosa with The Naked Scientists

Andi MSkilton14 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.

After 50 years, Inherited Retinal Disorders are Now the Leading Cause of Blindness in People of Working Age!

Andi MSkilton8 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.

New Breakthrough: Transplantation of Photoreceptors from Retina Grown ‘in a dish’

PrateekBuch22 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

It’s OK to Ask About Clinical Research – an NIHR Campaign

PrateekBuch16 May 2013


We are backing a campaign run by the National Institute for Health Research (NIHR) called “It’s OK to ask,” which encourages patients to ask their doctor about clinical research.

Clinical research is a vital tool for gathering evidence, which we can use to develop better treatments. Our group focuses on therapies for sight loss, but the process of promoting, conducting and using clinical research to improve healthcare is crucial to the whole of the NHS and to medical science in general.

In many cases doctors will approach patients about taking part in research, but the Gene and Cell Therapy Group agrees with the NIHR that patients and carers should feel empowered to ask about clinical research too. It is crucial that as patients, we all feel confident to ask about the latest research into conditions that affect us or our friends and families, and about opportunities to participate in future studies.

Asking your doctor or healthcare professional about research will enable you as a patient to engage with progress in medicine by staying up-to-date with the latest findings and by helping to contribute to tomorrow’s advances.

That’s why during 2013/14 the NIHR is promoting the fact that it’s OK to ask about clinical research.

If you have a medical condition and are undergoing treatment, they would like you to ask your family doctor, nurse or consultant about clinical research, and whether it might be right for you.

Many of you already ask us about research into treatments for sight loss and we endeavour to provide as much information as we can about our work and how to engage with it through our website, this blog, and by directly answering your queries. In endorsing this NIHR drive for more patients to ask about research, we would like you to encourage others to do the same – there are many ways in which you can ask us about our research, including on Facebook, Twitter and by email.

You can also let the NIHR know if you do ask your doctor about research into any condition, and what happens when you do. You can find the NIHR’s campaign on Facebook, on Twitter using #NIHRoktoask, by email or by telephone (0300 311 99 66). You could even share your story about how you got in touch with the EyeTherapy group at UCL Institute of Ophthalmology!

We hope that through this campaign, which coincides with International Clinical Trials Day on May 20th, you feel encouraged to ask your doctor about clinical research – remember, “it’s OK to ask!”