Can Gene Therapy Provide a Cure for Retinal Disease? An Early-Stage Clinical Trial Says “Maybe”

retina with choroideremia

A group of international researchers from the United Kingdom, the United States, the Netherlands, and Portugal have used gene therapy in a clinical trial to treat a small group of male subjects with choroideremia, a rare degenerative eye disease.

This early-stage clinical trial demonstrates potential for the use of gene therapy to treat a number of additional retinal diseases, including age-related macular degeneration.

The research, entitled Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial, was published online in the January 2014 issue of The Lancet. The Lancet publishes a weekly journal and six monthly specialty journals in the fields of global health, diabetes and endocrinology, oncology, neurology, respiratory medicine, and infectious diseases.

The authors are Robert E. MacLaren, Markus Groppe, Alun R. Barnard, Charles L. Cottriall, Tanya Tolmachova, Len Seymour, K. Reed Clark, Matthew J. During, Frans P. M. Cremers, Graeme C. M. Black, Andrew J. Lotery, Susan M. Downes, Andrew R. Webster, and Miguel C. Seabra, who represent the following institutions: University of Oxford, UK; Moorfields Eye Hospital, London, UK; Imperial College London, UK; Nationwide Children’s Hospital, Columbus, Ohio; Ohio State University Medical Center; Radboud University Medical Center, Nijmegen, Netherlands; St.Mary’s Hospital, Manchester, UK; University of Southampton, UK; University College London; and Universidade Nova de Lisboa, Lisbon, Portugal.

About Choroideremia

Choroideremia (kor-oy-dur-EE-mee-uh) is an X-linked recessive retinal degenerative disease and a rare inherited genetic disorder that causes progressive loss of vision due to degeneration of the choroid (the blood vessel layer of the eye) and retina (the light-sensitive nerve tissue in the eye). It affects males predominantly. Choroideremia is also referred to as CHM, because it is caused by a mutation in the CHM gene.

In childhood, night blindness is the most common initial symptom. As the disease progresses, there is loss of vision, frequently starting as an irregular ring that gradually expands both in toward central vision and out toward the extreme periphery.

The Choroideremia Research Foundation describes it as follows:

Choroideremia is a [genetic] eye disease that causes retinal degeneration and blindness. It is X-linked recessive, which means that normally males exhibit the disease and females are carriers (on their X chromosome). In rare cases, females are also affected. Night blindness is an early symptom of choroideremia, followed by loss of peripheral vision, depth perception, and eventual blindness. Intermediate stages of the disease include loss of visual acuity and color perception.

About the Research

From Gene Therapy May Help Against Rare Blinding Disease at WebMD:

[Lead author] MacLaren and his colleagues engineered a virus that would infect the patient’s retina but, instead of spreading disease, would instead release a DNA payload that would replace the defective gene with a working copy of the gene.

The phase 1 clinical trial involved six patients aged 35 to 63 – two with excellent vision, two with good vision, and two with damaged vision. In an operation similar to cataract surgery, doctors surgically detached the patients’ retinas and then injected the virus underneath, using a very fine needle.

Six months after the operation, patients with good or excellent vision retained that vision, but could see more in the dark when tested. Loss of night vision is an early sign of the disease, MacLaren said.

The two patients with damaged vision experienced improvement and were now able to read two and four more lines on [an eye] chart. Those improvements have lasted for two years in one patient and one year in the other, researchers reported.

“It’s too early to say the degeneration has stopped, but the vision we’ve seen in these two patients has been sustained at one year and two years,” MacLaren said in an interview.

A Research Summary from The Lancet

From Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial:

Methods: In a multicentre clinical trial, six male patients (aged 35-63 years) with choroideremia were administered [the engineered virus, via injection]. Visual function tests included best corrected visual acuity, microperimetry [a measurement of the regression or progression of retinal visual function], and retinal sensitivity tests for comparison of baseline [measurements] with six months after surgery.

Findings: Despite undergoing retinal detachment, which normally reduces vision, two patients with advanced choroideremia who had low baseline best-corrected visual acuity gained 21 letters and 11 letters (more than two and four lines of vision). Four other patients with near normal best-corrected visual acuity at baseline recovered to within one to three letters.

Interpretation: The initial results of this retinal gene therapy trial are consistent with improved rod and cone function that overcome any negative effects of retinal detachment. These findings lend support to further assessment of gene therapy in the treatment of choroideremia and other diseases, such as age-related macular degeneration.

Meet Josh Crary, Who Has Choroideremia

Josh Crary

“My vision problems started at birth. I had very poor eyesight and wore glasses from a very early age. When I was 13, my vision became really bad and I had to see a specialist, who made a drastic change in my prescription and diagnosed me with choroideremia (CHM). We did some family research and found that I’d inherited it from my mother. During the day she’s fine, but she has difficulty driving when it’s dark.”

“I was really upset when I realized my vision was going to continue to get worse. The way I handled it wasn’t the best – I was in big-time denial. I didn’t tell many people that I had problems seeing. When I was younger I really didn’t need too much assistance and could ‘hide’ it – or at least I thought I could.”

“Ten years ago I wouldn’t have admitted this, but when I think back, I wish I’d been a bit more open with my friends. I know they wanted to help me. There were many times when I needed help and didn’t ask for it. I just wanted to be ‘normal’ and not some kind of poster child.”

You can read Josh’s story in its entirety at the VisionAware website. You can reach Josh at

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