Media

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, professor of ophthalmology at the University of Oxford and an honorary consultant at the Oxford Eye Hospital and Moorfields Eye Hospital, who is leading the trial.

Jonathan Wyatt, 63, an arbitration lawyer from Bristol had the surgery at the Oxford Eye Hospital based at the John Radcliffe – the main NHS centre for this trial. He is the first of 12 people in this initial human trial that will receive the novel gene therapy.

Mr Wyatt was diagnosed with choroideraemia in his late teens and has suffered progressive sight loss ever since. He now has limited vision as a result of the degeneration and his dark adaptation is poor.

Choroideraemia is a genetic disease that leads to progressive degeneration of the retina in the eye. It generally affects males only and there is no treatment. The diagnosis is usually made in childhood and leads to blindness in men by their forties. It occurs due to deficiency of the REP1 gene located on the X chromosome.

The novel gene treatment was developed by Professor MacLaren at Oxford University in collaboration with Professor Miguel Seabra at Imperial College London. It is designed to provide the gene missing in people with choroideraemia to stop the deterioration that gradually leads to blindness.

It uses a virus essentially as a delivery vehicle that ferries DNA including the missing gene into the right part of the eye. The virus has been engineered to infect the light-sensitive cells in the retina known as photoreceptors. There the gene is switched on and becomes active.

With this particular gene therapy, the treatment could provide a one-off permanent correction of the disease because the gene is thought to remain in the retinal cells indefinitely.

‘This trial represents the world’s first ever attempt to treat this disease and the first time that gene therapy has been directed towards the light-sensitive photoreceptor cells of the human retina,’ says Professor MacLaren. ‘This represents a major breakthrough and is highly significant for patients who are losing sight from other photoreceptor diseases, such as retinitis pigmentosa.’

The trial will see 12 patients undergo surgery in which the gene therapy is injected into one eye. The other eye would then act as a control against which to assess any treatment effect. The researchers would however aim to go on to treat the second eye, should the treatment be proven to be effective.

The aim of the trial is primarily to assess safety, but it will also gain initial data on how effective the treatment is. The researchers estimate that it will take two years to know whether or not the degeneration has been stopped completely by the gene therapy.

‘While safety appears so far to be fine, the efficacy of the gene therapy will only be evident after 24 months. We need this time to measure any effect as the degeneration caused by choroideraemia is slow,’ explains Professor MacLaren.

The clinical trial is funded by a grant awarded to the University of Oxford by the Health Innovation Challenge Fund – a translational award scheme funded jointly by the Wellcome Trust and the Department of Health.

Professor Seabra, who played a key role at Imperial College London in identifying the gene causing choroideraemia and in eliciting the mechanism of cell death in the retina, comments: ‘The ability to offer a gene replacement treatment for these patients was the final objective of 20 years of intense research in my laboratory. This is a moment of fulfilment for us and a dream come true for all choroideraemia patients.’

Photos courtesy of BBC News are available at: http://www.ox.ac.uk/media/news_releases_for_journalists/111027_1.html

For more information please contact Professor Robert MacLaren at enquiries@eye.ox.ac.uk

The University of Oxford press office on 01865 280530 or press.office@admin.ox.ac.uk

Or the Oxford Radcliffe Hospitals NHS Trust media office on 01865 231471 or mediaoffice@orh.nhs.uk

Please note that any enquiries regarding the patient Mr Wyatt need to go through Oxford Radcliffe Hospitals.

Notes for editors

  • BBC News is reporting on this story this evening from 5pm, having identified the story and worked with the researchers on it.
  • There is an email address for patients wanting to find out more about the trial: OEHResearch@gmail.com.
  • The research team is still recruiting patients to the trial. While this initial trial will involve only 12 people, further trials may well follow. Patients are recruited through the four NHS centres participating in the trial depending on where in the country the patients are based.
    The four centres are the Oxford Radcliffe Hospitals NHS Trust, Moorfields Eye Hospital NHS Foundation Trust, Manchester Royal Eye Hospital and Southampton University Hospitals NHS Trust.
    All patients will receive their gene therapy treatments in Oxford, but will be followed up in the years after at one of the four referring centres. That way it is easier for patients who live a long way away.
  • Professor MacLaren explains that gene therapy is ideally suited to the eye because:
    1) ‘Most of the incurable causes of blindness are genetic and correcting the genetic defect is the most logical treatment;
    2) ‘Only a small dose of the gene therapy is needed in the eye, compared to the liver or lung, for instance, where up to ten thousand times as many viral particles would be needed to get an effect;
    3) ‘The eye is relatively separate from the immune system, which reduces the likelihood of an immune reaction to the viral gene therapy;
    4) ‘The cells in the eye do not divide, which means we can use a viral vector which does not interfere with the DNA in the host cells. This also makes it much safer. Effectively we are creating an extra mini-chromosome that carries the missing gene.’
  • Much of the preclinical work for this study has been done using new gene therapy techniques applied to human cells in tissue culture, which has dramatically reduced the need for animal research in gaining the necessary safety data ahead of this first trial in humans.
  • The trial is sponsored by the University of Oxford and is funded jointly by the Department of Health and the Wellcome Trust through the Health Innovation Challenge Fund.
  • Oxford University’s Medical Sciences Division is recognized internationally for its outstanding research and teaching, attracting the brightest minds from all over the world.
    It is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students, and brings in around two-thirds of Oxford University’s external research income. Listed by itself, that would make it the fifth largest university in the UK in terms of research grants and contracts.
    Oxford is home to the UK’s top-ranked medical school, and partnerships with the local NHS Trusts enable patients to benefit from the close links between medical research and healthcare delivery.
    14 winners of the Nobel Prize for Physiology or Medicine worked or were educated at Oxford, and the division is home to 29 Fellows of the Royal Society and 68 Fellows of the Academy of Medical Sciences.
    The development of penicillin at Oxford ushered in the modern age of antibiotics, and the confirmation of the link between smoking and cancer has prevented many millions of deaths. Oxford continues to be at the forefront of medical research, whether it’s the genetic and molecular basis of disease, the latest advances in neuroscience, or clinical studies in cancer, diabetes, heart disease and stroke. Oxford has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic.
    A great strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions.
  • The Health Innovation Challenge Fund (HICF) is a parallel funding partnership between the Wellcome Trust and the Department of Health. The funders are collaborating to stimulate the creation of innovative healthcare products, technologies and interventions, and facilitate their development for the benefit of patients in the NHS and beyond. The HICF operates a succession of thematic calls for proposals, each selected to focus on unmet needs in healthcare relevant to the NHS, and will support innovative developments that are within three to five years of launch or adoption. www.hicfund.org.uk 
  • The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. www.wellcome.ac.uk
  • The Department of Health (DH) works to improve the health and well-being of people in England. The Department sets overall policy on all health issues and is responsible for the provision of health services through the National Health Service. www.dh.gov.uk