New developments in the search for treatments for Stargardt disease

Posted on: Thursday, January 31st, 2019

Researchers funded by Retina UK have contributed to the early development of potential new treatments for Stargardt disease, with their findings recently published in the journal Genetics in Medicine.

Stargardt disease principally affects central vision, with onset usually occurring during adolescence or young adulthood, and is frequently caused by errors in a gene known as ABCA4. However, in many cases, no faults can be found in the sections of the gene that code for the building block ‘ingredients’ of the ABCA4 protein, meaning that there are no clues to guide scientists in the development of treatments. Profs Frans Cremers and Rob Collin, at Radboud UMC in The Netherlands, are leading a team searching for hidden mutations in these cases.

A regular genetic test only examines part of each gene, disregarding non-coding sections known as ‘introns’. These sections are ‘edited out’ during protein construction by a process known as splicing. However, mutations within introns can still have a significant influence on how the coding regions are edited and interpreted by the cell’s protein-building machinery, often resulting in a faulty protein.

With the help of funding from Retina UK, the researchers have developed a fast, cost-effective method of scanning the entire length of the ABCA4 gene, including the introns. The team’s new method has enabled them to find several intron mutations in cells from people living with Stargardt’s and they have gone on to develop a kind of molecular patch, described as a “band aid”, to cancel the harmful effects of these mutations.

“Errors in the DNA cause a disturbed function of the proteins in our eyes” explained Prof Collin. “With such a ‘band-aid’ we can block the mistakes, and by masking the mutations, the cells will eventually start producing good proteins again.”

The band aid is made from a synthetic form of RNA, the molecule that acts as an intermediary to translate the genetic code in DNA into proteins. It is delivered to the retina via an injection into the eye. This RNA molecular patch approach has already proved successful for other conditions such as Leber’s Congenital Amaurosis, where it is showing promise in clinical trials. However, each different mutation requires its own specific band aid, so obtaining a genetic diagnosis will be essential for those living with inherited retinal disease who may be able to benefit from these treatments in future. You can read more about genetic testing here.

Retina UK has been able to contribute to this ground-breaking research thanks to your generous support. Help us maintain the momentum in the search for treatments.