Let’s Chat About…Gene Therapy News for LCA13, LCA1, LCA2, and LCA4

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One of Britain’s top ophthalmologists delivered promising research news on several forms of Leber congenital amaurosis, including LCA13 (RDH12), LCA1 (GUCY2D), LCA2 (RPE65), and LCA4 (AIPL1).

Prof. Michel Michaelides, with more than a dozen LCA studies and clinical trials in the works, shared the news in a recent Hope in Focus webinar episode called Let’s Chat About…Gene Therapy for LCA.

Dr. Michaelides affably covered a range of topics, from preclinical molecular studies and research heading into human trials, to types of gene therapy and the importance of patient voices in developing treatments and cures for LCA and other rare inherited retinal diseases (IRDs). You can click here to view the session.

Dr. Michaelides is Head of Clinical Ophthalmology at MeiraGTx, where he is a founding member. He is a Professor of Ophthalmology at University College London Institute of Ophthalmology in the Department of Genetics. He also serves as a Consultant Ophthalmologist at Moorfields Eye Hospital in the departments of Inherited Eye Disease, Medical Retina, and Paediatric Ophthalmology.


Prof. Michel Michaelides

Based in the United Kingdom, Dr. Michaelides received a career development award – an honor rarely given to applicants outside the United States – from the Foundation Fighting Blindness. He also received fellowships from Moorfields and the Casey Eye Institute.

He gave a glimpse of the ophthalmic work in progress at MeiraGTx, a clinical-stage gene therapy company headquartered in New York and London. The biotech focuses on developing potential curative treatments for patients living with serious diseases, including IRDs and Age-Related Macular Degeneration.


LCA13 (RDH12):

Research into LCA13 (RDH12) is progressing, with an ongoing natural history study underway in the UK and US, and clinical trials in the offing.

“In terms of a treatment trial, there are plans to initiate a trial in 2022,” Dr. Michaelides said.

The prospective natural history study has sites in London and Michigan, with potentially more European and US sites opening.


MeiraGTx researchers presented preclinical work on LCA1 (GUCY2D) at the European Society of Gene and Stem Cell Therapy. The studies included retinal organoid work, which is where researchers study a retina in a dish, a retina generated from patient cells.

“These are often generated from skin or blood cells, and that allows you to recapitulate the retinal condition in a dish and tryout different therapies,” he said. “Preclinical data is promising and supports development of a gene therapy for GUCY2D.”

LCA2 (RPE65):

Researchers presented Phase 2 promising data on what Dr. Michaelides called an optimized strategy in treating LCA2 (RPE65). Meira is gearing up for a pivotal Phase 3 clinical trial, beginning the first half of this year. Researchers also are conducting an RPE65 natural history study to find out more about the effects and progression of the disease on patients.


MeiraGTx is also conducting a study on LCA4 (AIPL1), an exceedingly rare and severe form of the disease in which children have profoundly reduced vision from birth.

“There is a narrow window of opportunity (for treatment) because the retina degenerates and thins out by the age of 4 years. Treatment needs to be before 4 years of age. MeiraGTx has manufactured a gene therapy that they are making available under a Specials license in the UK.”

So far, four children have been treated with the unlicensed medicine or what is known as compassionate-use therapy because of the limits in administering the treatment. All four have been from abroad, with one from the US, however, any ability to track the children’s progress has been stalled by travel restrictions imposed because of the COVID-19 pandemic.

“We haven’t been able to see them again to see to what extent it has had any beneficial effect. There haven’t been any safety concerns, but we haven’t really been able to determine whether it’s working as yet.”

The treatment is available globally to any child, but for now treatments have halted because the London hospital where the children underwent surgery no longer has the capacity to do more treatments.

A search for another UK site continues, but Dr. Michaelides told the webinar questioner with a child living with AIPL1 to contact him or MeiraGTx to learn more about the treatment.

LCA Gene Therapies

Dr. Michaelides also described the types of gene therapy.

LUXTURNA®, the only gene therapy federally approved for any inherited condition in the United States, targets a form of LCA caused by the RPE65 gene. People with RPE65 cannot make a protein needed by the retina, tissue at the back of the eye that converts light into signals to the brain, enabling sight. The therapy, developed by Spark Therapeutics, involves injecting under the retina in each eye a human-engineered virus containing copies of a normal gene, so cells can express the protein.

Another type of therapy performs like genetic tape, targeting a specific mistake and sending a message trying to correct the mistake.

ProQR in the Netherlands uses ribonucleic acid (RNA) ocular therapies. Unlike gene therapy that provides new DNA to cells (e.g., LUXTURNA®), RNA therapy modifies or provides RNA to patients’ cells. The company is working on the treatment for LCA10 (CEP290) that entails repeated serial intravitreal (into the jelly of the eye) injections that target the faulty message of the CEP290 gene.

“It targets a common specific sequence variant in the CEP290 gene; it targets the message, trying to correct the message, and because it’s the message, you need to keep repeating those injections on a several-monthly basis.

“The Phase 3 trial running at the moment is fully recruited and one expects readout from that trial some time in 2022.”

A third type of therapy is gene editing that corrects a genetic fault at the level of the genetic DNA blueprint. The biotechnology companies Editas Medicine of Cambridge, Mass., and Allergan of Ireland are working on the CEP290 mutation using gene-editing technology called CRISPR, which entails finding a specific bit of DNA inside a cell and using gene editing to alter that piece of DNA.

“So rather than the message, they’re actually going to the blueprint,” he said.

The treatment, characterized as one-and-done, is done by subretinal injection.

Patient Voices Vital to LCA Research and Treatments

Dr. Michaelides also emphasized that finding new LCA treatments and cures fundamentally depends on the voices of patients.

“There’s nothing more important,” he said. “And I’m not saying this because I’m on this Zoom. Patients teach me about their conditions.”

As medicine has evolved, so has the patient community and the medical community.

“We’re in a very different era from when I started training. When I started, ‘the doctor knew everything. We’re the experts. We don’t need anyone else’s help.’ We’re a long way from that now. It’s OK not to know everything; it’s a relatively new thing, to not need to appear to know everything.”

Research now requires a team effort where everyone brings something to the table: “It’s a win-win. Buy into the study; key to designing it; perform better on assessment; gather more useful information.

“It’s really important to listen to the patients; they’re going to give you all the information you need.”

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