A highlight of our Annual General Meeting was a lengthy discussion about our Target 5000 research project, between Fighting Blindness members, Dr. Paul Kenna and Mr. David Keegan (pictured left).
We opened our discussion with Paul Kenna leading us through the history of the project which began with Professor Pete Humphries in Trinity and his team’s breakthrough discovery in 1989 showing that rhodopsin was the first gene responsible for any type of retinitis pigmentosa (RP). David Keegan acknowledged what a huge contribution this initial identification made in opening doors for Irish ophthalmology researchers on a global stage and how it has been so influential to the work that has followed.
Although this research occurred 25 years ago, Paul explained that through Genable Technologies, they are now developing gene therapy based medicines for rhodopsin linked dominant RP that will soon enter clinical trials. He also emphasised the huge contribution to research that Fighting Blindness investment has made in gene discovery and research into inherited retinal degenerations that has led us to this new frontier in medicine.
What is Target 5000?
“There are many treatments that are in clinical trials for these varied conditions; however entry into many of these trials will require that the causative gene be identified for each person” explained Paul. David emphasised again the importance of the project; “Nobody with an inherited retinal degeneration truly has a precise diagnosis unless that person knows which gene is responsible for their condition.”
David and Paul also explained that sometimes when they look at the back of the eye they are happy that they can diagnose a specific condition, but when the gene sequencing is performed it can often come back with a completely different diagnosis as the genetic diagnosis is more specific than any eye exam available. They also described that there are now 180 genes known to be associated with inherited retinal degenerations and this number will top 200 soon.
Both doctors were in agreement on their focus for Target 5000 saying “The last thing we want is for Irish patients to be hearing about clinical trials and not able to access them”.
Questions From Fighting Blindness Members
How is this testing different to previous blood samples I may have given for research in the past?
Paul Kenna: In essence the objective of this study is essentially the same; we trying to find the gene and show that a mutation within it causes the condition. What has changed is that the technology has improved drastically. It used to be laborious to perform gene hunting, and that is why it was easier to look in large families. We were actually quite successful with this method and we identified three previously unknown genes. As a result of improved technology, it is now possible to give a genetic diagnosis to 60-70% of people, and it is only a matter of time before they find them all. To put this in context, when the first entire human DNA sequence was worked out 10 years ago, it took 10 years to complete and $3 billion. We can now sequence a sample in a matter of days for $5,000.
Why do we need to have an eye exam along with giving a blood sample?
David Keegan: The eye exam is as important as the blood sample for DNA sequencing, as neither test gives us a full clinical detail on its own. We only get the full picture when these are tied together delivering the most precise diagnosis possible.
What has been the progress with Target 3000?
Paul: We have been recruiting patients for the past few years from all over the country. The reason that a person needs to attend either my own or David’s clinic is because the electrophysiology test is an important part of the eye exam and there are relatively few places in Ireland this can be performed.
We have started to get information back from our first pool of patients, but this is not a quick process. In about 60% of cases, we would estimate that the gene would be one that has been previously shown to be causative and linked to a retinal degeneration. Even in this best case scenario, it can take a year to validate the result.
In most other cases, there may be four or five genes that could be causative – because we know that we are only looking for one gene, we then generally go out to the wider family in order to identify the true cause for the retinal degeneration. It does still take time, and there are no quick answers, but we need to be extremely sure of any result we give back to our patients. This is an academic project at present and there is an onus on us and a responsibility to deliver the best information back.
David: A lot of the work has been laid down by Professor Jane Farrar and Paul in Trinity, the groundwork and the logistics. We have worked out the responsibility of giving a putative diagnosis, the handling of the bloods and finding out the gene. We are consulting with Professor Andrew Green in Our Lady’s Hospital Crumlin regarding genetic counselling and through Fighting Blindness support we have been able to hire two clinical fellows to assist in the clinics.
I was initially told that numbers were restricted for this study– Can I now take part?
Initially we had restricted the numbers of people to this study to work out some of the logistics, but this is no longer the case. If you have an inherited retinal degeneration, and you would like to take part then you should contact us.
Should a whole family present together at the clinic?
The affected person who wishes to take part in the study will be tested to begin with and the rest of the family doesn’t need to be present at this clinic together. Once the first affected member is tested then arrangements can be made for the rest of the family to be seen. It’s also worth bearing in mind that, if possible, having information about your family tree when it comes to sight loss will help greatly at this stage.
Are people with recessive RP included in this study?
We actually have already included a number of individuals with recessive disease in Target 3000. For this study it doesn’t really matter whether the condition is dominant, recessive or X-linked. We want to see everyone and include everyone. It may be more difficult to find the gene but we want to be inclusive.
I think a close relative or friend of mine should take part in Target 3000, but they don’t seem keen – can I sign them up?
Consent of the affected individual to take part in Target 3000 is crucial. We cannot sign anyone up to take part in the project without their approval. Fighting Blindness are always here to talk to anyone about the process if this is required.
I’m on the list and I haven’t been called? / How do I check if I’m on the list?
For either of these scenarios please contact Fighting Blindness Research Manager Maria Meehan on 01 6789 004 or firstname.lastname@example.org to check your status.