Millions of people worldwide suffer from vision-threatening inherited eye diseases. Recent breakthroughs in genetics have identified the molecular biology cause of disease in many patients, however too large proportion still lacks a genetic diagnosis. Understanding the pathological process in molecular biology level gives important information how the disease manifests and progresses. Knowing the genetic cause of disease is also the first crucial step of developing novel therapeutic applications. By applying a translational approach, Dr Kaukonen’s group aims to identify new genes and gene variants accountable for inherited eye diseases, and to develop novel therapeutic approaches to treat them.
People are not the only ones affected with inherited diseases: e.g. purebred pet dog populations have accidentally been enriched with spontaneous recessive mutations as a result of the breed-creation schemes. To date, over 550 disease-causing gene variants have been reported (www.OMIA.org) – and the diseases and genes are very similar to those observed in people. Due to its unique genome structure, public health information databases and large dog DNA biobanks (such as the famous one in Helsinki, www.koirangeenit.fi), gene mapping is facilitated in dogs.
Dr Kaukonen combines veterinary ophthalmology expertise to state-of-the-art genomic analyses, and has successfully characterised several novel spontaneous canine models, new genes and even a novel mode of maternal inheritance to different inherited eye diseases. Key collaborators in this program include Prof Hannes Lohi and the clinicians in the Finnish Veterinary Ophthalmology Consortium, which she leads.
For long, safe and effective treatments were lacking for inherited eye diseases. However, in 2017, the world’s first gene therapy drug, Luxturna®, was approved to treat patients with RPE65 mutations causing inherited retinal degeneration. Another important milestone was met in 2020, when Jennifer Doudna and Emmanuelle Charpentier were awarded the Nobel Prize in Chemistry on their discovery of CRISPR-gene editing that enables direct and permanent correction of mutations in patient DNA. Since these breakthroughs, multiple other gene therapies have been approved and more are in clinical trials. However, majority of patients with inherited eye diseases still lack curative treatment – something Dr Kaukonen’s group in its part is aiming to change for better.
Inherited retinal dystrophies are usually genetically heterogenous, however situation in Finland is somewhat different with a strong founder effect of pathogenic variants in the CERKL gene. We are currently developing new gene replacement and gene editing vectors to develop novel treatment for CERKL-associated retinal dystrophy. We are also characterising the pathogenic CERKL variants in further details. Key collaborators in this program include Prof Robert E. MacLaren group at the University of Oxford, Docent Joni Turunen group at the Folkhälsan Research Center, Docent Kirmo Wartiovaara group at the University of Helsinki and Assoc Prof Soile Nymark group at the Tampere University.