From the lab to the clinic: A/Prof Fred Chen

Unlocking the secrets of Stargardt disease

Stargardt disease is the most common form of juvenile macular disease, with many children being diagnosed before they even leave primary school. But despite its prevalence, this genetic disease often goes undiagnosed or is misdiagnosed.

Perth ophthalmologist and MDFA Research Grant recipient Associate Professor Fred Chen is working both to find treatments and to establish clinical pathways for patients.

“My one wish as an ophthalmologist and researcher in macular disease is that one day I can tell my patients, who are affected by whatever form of macular degeneration, that we have the treatment to prevent them from going blind, or to restore their vision.”

A/Prof Fred Chen

Stargardt disease – also called Stargardt dystrophy or fundus flavimaculatus – is a genetic eye disease caused by more than 1000 different mutations, or faults, within a single gene called the ABCA4 gene. It affects one in every 10,000 people, and is the most common of the 250 types of inherited retinal diseases that blind 15,000 Australians.

MDFA funding allowed A/Prof Chen to examine the vast spectrum of Stargardt disease in more than 100 patients in his dedicated retinal dystrophy clinic at the Lions Eye Institute (LEI).

Some of these patients lost their vision when they were as young as seven, while others only noticed symptoms in their 70s, when the condition may masquerade as AMD. This extreme spectrum of disease manifestation is due to the large number and varied severities of mutations of the ABCA4 gene, which causes the condition.

As well as identifying several new mutations of this gene, A/Prof Chen’s team used patients’ own skin cells to study the effect of different genetic faults to develop personalised treatments for these mutations.

Testing on minature retinas, grown in the lab

Through this project, A/Prof Chen and his team were able to grow miniature retina from skin cells. This will enable them to test and modify drugs using cells in the laboratory rather than using an animal model or risking patients’ eyes in the early stages of the development.

Alongside collaborators at the Australian Inherited Retinal Diseases Registry, Genetic Services of WA and Murdoch University, A/Prof Chen has also established a streamlined clinical pathway for assessing and diagnosing these patients.

People living with Stargardt disease are sometimes undiagnosed or misdiagnosed, so this pathway helps to identify and manage them correctly. These patients can then receive genetic counselling so they and their family can better understand the disease, as well as be considered for clinical trials.

Following A/Prof Chen’s MDFA project, LEI has been chosen as one of two clinical trial sites for Stargardt disease treatment in Australia, and in 2021, they are recruiting children with the condition for a clinical trial of a new drug that may prevent progression of the disease.

A/Prof Chen’s team earned an NHMRC Ideas Grant in 2020 and a Bowen Foundation Grant in 2021 to continue this ground-breaking work, which gives hope for an effective treatment in future.

Learn more about what makes A/Prof Chen tick, in this interview from 2017, when he was awarded the MDFA Research Grant.

Posted: 14 June 2021. This article first appear in our publication 10 Years of Impact: Reflecting on the impact of investing into macular disease research.