Researchers at University College London’s Institute of Ophthalmology have successfully performed a proof-of-concept study that has highlighted the potential for a new treatment for Fuchs endothelial corneal dystrophy (FECD).
Funded by Fight for Sight, the study was published in The American Journal of Human Genetics and highlighted the potential of a targeted antisense oligonucleotide (ASO) therapy to treat FECD patients with a mutation in the TCF4 gene.
FECD affects the inner layer of the cornea, with patients usually showing symptoms at the age of 50 and over. Currently, the only treatment for the condition in order to restore vision and prevent blindness is corneal transplantation.
Leading the study, Dr Alice Davidson aimed to identify both known and new genetic causes of corneal endothelial dystrophies (CED) and find out if there is an overlap of relevant genes between common and rare types of CED.
Dr Davidson’s work was supported through an early career investigator award from Fight for Sight.
The study demonstrated that the formation of RNA aggregates have a toxic effect and underlie the pathology of FECD.
Using a corneal endothelial cell (CEC) model derived from FECD patients, Dr Davidson revealed that the repeated expansion of three DNA bases, known as a triplet repeat, results in the formation of the toxic nuclear RNA aggregates.
She also found that antisense oligonucleotide (ASO) treatment resulted in reduced RNA aggregates in patient cells, and a reduction in the toxic downstream effects of the RNA foci.
As an ASO-based treatment, Dr Davidson believes that it could offer an innovative therapeutic approach to benefit the majority of individuals affected by the condition.
Dr Davidson explained: “We have developed an ASO drug which targets a specific genetic mutation that is responsible for approximately 75% of FECD cases. Using patients’ corneal cells grown in the lab, we have demonstrated the utility of this treatment and with continued research and investment we hope our proof-of-concept study will pave the way for a new effective and less invasive way to treat this common and sight-threatening condition.”