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Exploring the Potential of Gene Therapy to Treat Autosomal-dominant Retinal Disease in a Mouse Model

Exploring the Potential of Gene Therapy to Treat Autosomal-dominant Retinal Disease in a Mouse Model content

Prof. Debra Thompson, University of Michigan, USA

Commencing in September 2019, this 1 year project is supported by Fighting Blindness. Led by Prof. Thompson, the team will study the a potential therapy to treat autosomal-dominant retinal disease in a mouse model due to mutations in the RPE65 gene.

Retinitis pigmentosa (RP) refers to a group of inherited retinal disorders that affect the light sensitive photoreceptor cells of the retina which are important for vision. This condition causes progressive vision loss, initially presenting with a loss of peripheral (side) vision and followed by a loss of central vision. RP is highly variable in terms of the age of presentation, rate of progression and inheritance pattern.

There are over 70 genes known to be associated with RP, one of which is RPE65. This gene which has received much attention in recent years plays an important role in your visual cycle. To date, just one specific mutation has been identified that results in an autosomal-dominant type of inheritance – specifically this is recognised in the medical and research community as RPE65-D477G. In dominant disease, only one affected copy of the gene is required to cause retinal degeneration.

Scientists across the globe are investigating novel approaches whereby they can replace the faulty gene with a new and healthy version, this process is known as ‘gene-augmentation’. However, it is not yet known or fully understood if this same method could be applied in dominant forms of disease. The present project wishes to explore this concept further.

Using a mouse model genetically modified to mimic autosomal-dominant RP, the researchers will deliver healthy RPE65 to the back of the mouse retina. Using normal and untreated mice as a control, they will then monitor and study the treated mice over a period of time to determine whether the delivery of new RPE65 can override the negative effect of a dominant mutation.