Target 5000 Project Update

Target 5000 aims to provide genetic testing for the estimated 5,000 people in Ireland who have a genetic retinal condition.

These conditions include, among others; retinitis pigmentosa (RP), Usher syndrome, Stargardt disease, Leber hereditary optic neuropathy (LHON), Leber congenital amaurosis (LCA), choroideremia, and retinoschisis.

Target 5000 is now an all-Ireland endeavour, with two sites in Dublin and one in Belfast. To date, almost 500 people have been tested.

Dr Paul Kenna, one of the clinicians carrying out the work, explains what is involved in the testing process: “A patient can expect an in depth clinical examination. This is then combined with a genetic analysis which allows us to examine in detail the sequence of individual building blocks; the two go hand in hand”

As part of our commitment to this project, Fighting Blindness is funding two clinical fellows. Dr Emma Duignan will be working with Dr Paul Kenna in the Eye and Ear Hospital, and Dr Tahira Saad with Mr David Keegan in the Mater Hospital. Their appointments to work specifically on Target 3000 will accelerate the process for patients.

Benefit for Patients – A Precise Diagnosis

Until now, one of the challenges confronted by someone with an inherited retinopathy was the lack of a precise diagnosis. It is often impossible to tell which specific type of retinal disease a patient has based on simply looking at the eye, because these are some of the most complicated of all genetic conditions, involving almost 200 genes.

Dr. Kenna explains this in more detail: “Target 5000 offers the possibility of genetic diagnosis for anybody in the country with a clinical diagnosis of inherited retinal degeneration. Ultimately, for any inherited retinal condition, the true diagnosis is at the genetic level. I see many patients where it is quite easy to make a clinical diagnosis of retinitis pigmentosa (RP) but we know that RP at a genetic level is extremely varied, with many different genes causing different forms. I can’t say which of the many genes could actually be causing the patient’s RP through a clinical examination: that can only be done at the molecular genetic level, by actually examining the genes. That essentially is what Target 5000 is.”

Dr Matthew Carrigan, a postdoctoral researcher working in the Genetics Department in Trinity College, Dublin, reaffirms the benefits for patients of taking part in the project: “This will give patients information about the heritability of their condition and enable a more accurate clinical diagnosis. Most importantly, however, it enables patients to access therapies targeted to specific genes and mutations, many of which are in the advanced stages of clinical trials right now.”

Benefits for Research – Access to Clinical Trials

We are entering an extremely exciting time in retinal research. Dr Kenna states: “When I started working with Fighting Blindness in the late 1980’s, it was a very exciting time for researchers but now it is a very exciting time for patients”. Research projects have now advanced through basic research to first stage clinical trials. Many of these therapies will rely on repairing the specific gene abnormality for each individual. This is why it is vital that we identify the exact genetic profile of people affected by retinal degenerative conditions.

Knowing which of your genes are affected and where the mutations occur in individual cases means arriving at a complete diagnosis. This information will lead to better future therapies and possible inclusion in future clinical trials.

DNA Sequencing

So how do they do it? The researchers use a process called DNA sequencing. Dr Carrigan explains how this process works: “The aim is to sequence DNA in order to find the mutation or mutations causing the condition. To achieve that goal, we’re using a targeted-sequencing approach, in which the “exons” of genes known to be involved in retinopathy are extracted and sequenced en masse. The data is then reassembled and computationally aligned to the human genome before being analysed for regions which do not match the “reference” sequence. This approach enables large areas to be covered at single-base resolution – even a single changed DNA letter can be sensitively detected by this technique.”

National Patient Registry

There is also another important aspect to this project and that is the creation of a patient registry of individuals in Ireland who have inherited retinal diseases. It is vitally important that we have a fully comprehensive list of all individuals in Ireland with these conditions as this will enable us to identify patients who are eligible for clinical trials, adding to the global bank of knowledge about inherited retinal conditions and ultimately advancing the progress of treatments and cures for blindness.

For more information about Target 5000 or to register your interest, please contact our research manager Maria Meehan on 01 6789 004 or target5000@fightingblindness.ie.