An interview with Professor Michel Michaelides

Groundbreaking clinical trial into leber congenital amaurosis

The secret to the professor’s success, he said, is to keep questioning. 

“One of my biggest learnings is to never take anything for granted or at face value, especially if there’s a dogma or a belief that this can’t be done or that something is impossible to treat. So, I guess it's always being a bit sceptical, critical and not taking anything for granted in terms of accepting that something can't be done.”

The best example of that, he said, is his research into one of the most severe forms of LCA, which is caused by the AIPL1 gene. The condition manifests at birth or early childhood.

Prof. Michel Michaelides was the lead investigator and lead author for a clinical study in a Lancet paper.

The trial restored vision to children who had previously experienced only light sensitivity.

Life-changing improvements in babies’ vision

Through a clinical study conducted at Great Ormond Street Hospital, four babies have experienced life-changing improvements in their vision following pioneering eye gene therapy.

The children went from only perceiving light to being able to see objects and record vision using standard child-friendly tests.

“There was no doubt, and you could see the behaviour was so dramatically improved. It's genuinely miraculous. The first time it really came home, we were presenting this at a closed meeting with retina specialists and a paediatric retina specialist came up to us and said, ‘you've cured blindness’.” Said Prof. Michaelides.

Lasting changes in vision

He added: “I just got an email today, actually, from one of the children, from the second group of 7 children treated, who's in Thailand, about how he is learning how to write. He's working on his handwriting. That would have been inconceivable, right? And the first children are out to five years now, so we know it lasts at least five years.”

Working in partnership

The revolutionary genetic treatment was delivered with experts from Moorfields Eye Hospital and University College London Institute of Ophthalmology, Great Ormond Street Hospital and The Evelina London Children’s Hospital, with the support of gene therapy company MeiraGTx.

Michel is a founding Member of the company and its head of clinical ophthalmology.

MeiraGTx was also awarded an Innovation Passport Designation for the gene therapy from the MHRA. The designation can accelerate the time to market and patient access. As a result, MeiraGTx is applying for marketing approval in the UK for its AIPL1 gene therapy. 

In the footsteps of legends: Professor Michaelides' early career

As a junior working in ophthalmology, he discovered a passion for understanding the retina, which he says he thought “was the most interesting bit of the eye.”

“It [the retina] was the underlying cause of the commonest causes of visual failure in the western world. There were laser treatments that could be done, which I enjoyed delivering and thought, ‘oh, I think I might want to specialise in the retina’.”

An introduction to research in inherited eye conditions

Prof. Michaelides took time out to dedicate two years to a research degree with Tony Moore at Moorfield Eye Hospital and UCL at the Institute of Ophthalmology. “At that time, I had no idea who Tony Moore was,” he said.

“He turned out to be a legend in the field of inherited retinal disease. And the project was on cone and cone-rod dystrophies. Those two years initiated my passion for inherited retinal disease.”

“We were very productive both in the laboratory in terms of molecular genetics and seeing lots of patients and families who were incredibly generous with their time.

"And so, I met a lot of people with different conditions. I learned a great deal about those conditions and published information to put out into the world and hopefully help others do more research and learn more about these diseases and give them greater visibility,” said Prof. Michaelides.

Achromatopsia work supported by Fight for Sight

It was while working with Professor Moore that Prof. Michaelides received the 2010 Hans and Mrs Gertrude Hirsch award for his research into new treatments for the inherited retinal disease achromatopsia.

Specifically, to explore gene replacement therapies for the condition, which impacts the cone photoreceptors and may be suitable for clinical trials. 

The award scheme, administered by Fight for Sight, was established with funding from the estate of the late Dr Hans Hirsch.

“Achromatopsia is the first condition that I became familiar with during my research degree, which is a bit ridiculous given it affects one in 30,000 people. So, it's one of the rarest conditions we see, but it's not rare for those patients. So, I got to do lab-based research,” said Prof. Michaelides.

“I was doing genetic screening for patients with achromatopsia. And it was painstaking. It took forever. So, I had panels of 50 patients who Tony had identified in clinic with clinically diagnosed achromatopsia.

I was involved in trying to identify the gene that caused their condition.”

“At that point, there were three genes that were known and one of those we identified at UCL. So, I was doing the genetic screening and then I was seeing patients clinically trying to discern between the different types of achromatopsia.

"To do that I was doing both colour vision and psychophysical testing with one of the legends in colour vision, John Mollon.”