Mertonians carry out world’s first gene therapy operation for common cause of sight loss

Tuesday 19 February 2019

Two Mertonians were behind a recent ground-breaking gene therapy trial for the disease known as age-related macular degeneration (AMD), the most common cause of untreatable blindness in the developed world. Professors Robert MacLaren (1992) and Peter Charbel Issa (2009) together performed the gene therapy surgery successfully last month at the Oxford University NHS Foundation Trust.

The procedure was carried out at the John Radcliffe Hospital, 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, a Bodley Fellow and Lecturer in Human Anatomy at Merton, said:

“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.”

*Photo of the back of the eye prior to gene therapy. The pale area in the centre is the macular degeneration. White spots known as drusen can also be seen. The optic nerve is to the left.*

Age-related macular degeneration (AMD) is the biggest cause of sight loss in the UK, affecting over 600,000 people. Dry AMD is a slow deterioration of the cells of the macula. It affects the central part of a patient’s vision with gaps or ‘smudges’, making everyday activities like reading and recognising faces difficult. If successful, the treatment could have a beneficial impact of patients’ quality of life and their ability to remain independent.

The first person to undergo the procedure was Mrs Janet Osborne of Oxford. Like many people with AMD, she has the condition in both eyes, but it is more advanced in her left eye. As is typical with this condition, the central vision in her left eye has deteriorated and is very hazy, although her peripheral vision is better. Her restricted vision makes household tasks such as preparing vegetables and sewing difficult, she cannot read for very long, and often finds it hard to recognise faces.

*Professors Charbel Issa (left) and MacLaren (right) perform the gene therapy surgery - Photo: © Jon Brett, Eye Research Group Oxford*

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, 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.

The virus ins injected into the eye through syringe which is connected to a hydraulic pump - © Jon Brett, Eye Research Group Oxford — *The virus ins injected into the eye through syringe which is connected to a hydraulic pump - Photo: © Jon Brett, Eye Research Group Oxford*

A key factor in AMD is the complement system, a system of proteins in our immune system that fights bacteria. In macular degeneration, these proteins are over-active and start to attack the retinal cells, in a similar way to how they would attack bacteria.

Professor MacLaren, who also ran the first gene therapy clinical trials from Oxford for rarer causes of blindness, Choroideremia and retinitis pigmentosa, explained:

“We’re harnessing the power of the virus, a naturally occurring organism, to deliver the DNA into the patient’s cells. When the virus opens up inside the retinal cell it releases the DNA of the gene we have cloned, and the cell starts making a protein that we think can modify the disease, correcting the imbalance of the inflammation caused by the complement system.

“The idea of this gene therapy is to ‘deactivate’ the complement system, but at a very specific point at the back of the eye, so the patient would otherwise be unaffected by it, and we hope that in future it will slow down the progression of macular degeneration.”

He added:

“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.”

Gene therapy first to 'halt' most common cause of blindness - BBC News
British woman is first in the world to undergo gene therapy for most common form of blindness - The Telegraph
Oxford woman first to undergo gene therapy - Oxford Mail
UK surgeons hail ‘world first’ op to tackle leading cause of sight loss - ITV News