First Trial for Choroideremia Begins in England
November 4, 2011 - The first ever trial of a therapy for choroideremia began last week in Oxford, England. Choroideremia is an inherited retinal degenerative disease that results in progressive degeneration of the retina. It is due to a mutation in the REP1 gene, which is located on the X chromosome (is “X-linked”). This means that it generally affects males. The diagnosis is often made in childhood and usually leads to blindness in a man’s forties.
The first patient to receive gene therapy for choroideremia, Mr. Jonathan Wyatt, was treated at the John Radcliffe Hospital in Oxford in a clinical trial led by Professor Robert MacLaren of Oxford University. Mr. Wyatt is the first of 12 people in this initial (Phase 1) human trial. Each patient will undergo surgery to inject the therapeutic replacement gene into one eye, while the other eye will go without treatment so as to act as a control. Should the treatment prove to be safe and effective, however, the study team would later treat the second eye.
“[Choroideremia] has been recognised as an incurable form of blindness since it was first described over a hundred years ago,” says Professor MacLaren. “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.”
The novel gene treatment was developed by Professor MacLaren, at Oxford University, in collaboration with Professor Miguel Seabra of Imperial College London. It is designed to provide the gene whose function is missing in people with choroideremia, to stop the deterioration that gradually leads to blindness.
The treatment uses a specially engineered virus (called a “vector”) to deliver the new replacement gene into the cells of the retina. The virus is designed to trick the light-sensitive cells in the retina, as the rod and cone photoreceptors, into taking in the virus, but it has been engineered not to reproduce itself or cause any disease. Once the vector has been taken into the rods and cones, the gene is switched on and becomes active. With this particular gene therapy, the treatment could provide a one-time permanent correction of the disease, because the gene is expected 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.’
Although the aim of this Phase 1 trial is primarily to assess safety, it is likely also to produce data suggesting how effective the treatment is. The researchers estimate that it will take years to determine how effective and lasting the gene therapy will be.
‘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 choroideremia is slow,’ explains Professor MacLaren.
Dr. Ian MacDonald is a Canadian researcher who studies choroideremia. He has played an important role in developing screening tests for the choroideremia gene. "For many of us, researchers, patients and families, this is such an important step forward. This is the culmination of over 20 years of work in various laboratories, having started with the discovery of the gene in 1990, to now a form of genetic therapy. It provides great hope for everyone."