TCD SCIENTISTS have made a breakthrough in tackling a common form of retinitis pigmentosa (RP) which can eventually lead to blindness.
The breakthrough tackles the rhodopsin gene alterations that cause the most common form of RP, which is an inherited condition. This form affects 19,000 people in the EU and 300 people in Ireland of the estimated 3,000 people who have RP in this country.
Rhodopsin-linked RP is variable and at least 150 different alterations in the gene have been identified in RP families worldwide. This makes developing a gene-based therapy very complex, if not impossible, if the treatment targets the specific alteration.
Researchers in the Smurfit Institute of Genetics in TCD have been working for 20 years to identify the genes and a potential treatment for RP. The condition is caused by gene mutations which lead to the degeneration of photoreceptors at the back of the eye.
The paper is being published today in the leading international gene therapy journal Molecular Therapy.
The research has been undertaken by a team led by Dr Paul Kenna, a clinical ophthalmologist, Prof Jane Farrar and Prof Peter Humphries. The senior research scientist in the team is Dr Sophia Millington-Ward. The research is funded by Science Foundation Ireland, Fighting Blindness Ireland and the National Neurovision Research Institute (US).
The rhodopsin-linked form of RP is caused by a mutant form of the rhodopsin gene. The therapy works by switching off both copies of the gene, the normal and the altered copies. Simultaneously, a replacement rhodopsin gene is introduced which has been subtly altered so it cannot be suppressed. It encodes normal protein which allows the photoreceptors to work normally. The research restored visual function in mice with a dominant rhodopsin-linked form of RP exactly replicating the form of the disease which affects humans.
It is hoped to trial the therapy on a larger mammal, probably a pig, and eventually move on to human trials.
Prof Farrar said the research’s implications stretched far beyond RP. “It is directly relevant. It pertains to a lot of dominant diseases potentially.” She said the key to finding a cure was to suppress the mutant gene causing the problems. As it is the dominant gene, it is harder to treat. “It is very exciting. It is the first time it has been shown that this approach works for what we call a dominant disease where the mutant protein is driving the disease process.”
