A genetic diagnosis for RP

James Birtley is a Retina UK supporter and volunteer who is living with retinitis pigmentosa. He is also a scientist with a particular interest in the structure of proteins, the complex molecules that form the building blocks of our bodies.

Earlier this year, James took up the opportunity attend a workshop in the USA focused on the specific gene that causes his RP. He has kindly written an account of this experience for us:

My life reached a major turning point in 2018 when I was formally diagnosed with retinitis pigmentosa (RP). The ophthalmic consultant at the John Radcliffe Hospital in Oxford recommended genetic testing and I enthusiastically accepted. But little did I know the exciting journey that this decision would take me.

The nurse took some blood and within a few months a letter arrived with an Oxford post mark. I was excited and nervous at its presence. The results were unambiguous and confirmed a long-held suspicion of familial autosomal dominant RP (my mum had RP too). I felt elated that they had identified the molecular reason for my eye disease and lucky to be one of the about 50% of patients to receive a genetic diagnosis. To get to this point, our amazing NHS screened my DNA against a panel of 111 eye genes of interest and they found I had a genetic alteration (a mutation) in an eye-cell membrane protein called peripherin 2 (PRPH2).

I had never heard of PRPH2. I then did what most people do in such circumstances and began to search the internet. The first ports of call were Google, Wikipedia, and PubMed. I could see a plethora of facts and information on this gene and hundreds of scientific articles explaining its involvement in rod and cone cell physiology and its association with eye disease when things go wrong. But this was not enough for me.

I then decided to extend my searches to RP groups on Facebook – crucially, there are several with more than 10,000 members each, spread across the globe. I searched the posting history using PRPH2 and quickly found and connected to individuals also affected by mutations in this gene. I never expected genetic networking to be so straightforward. I exchanged many messages including hundreds with the California-based Ken MacKenzie, who also has a mutation in PRPH2 and is active in making a difference medically in this space. He had already found many others affected by mutations in PRPH2 before I arrived on the scene. He also had the good fortune to connect with the Nixons, a wealthy family based in San Diego, also afflicted with a mutation in PRPH2. Importantly, they established the Nixon Foundation which specifically funds PRPH2 research. They are highly proactive in this space and are funding high impact research to make a difference by forging collaborations with the US-based Foundation Fighting Blindness and the Shiley Eye Institute at the University of California San Diego.

In March 2023, the Nixon Foundation funded a PRPH2-focused three-day workshop at the Hilton Torrey Pines, in La Jolla – one of the world epicentres for academic and commercial biomedical research. The ultimate aim of the workshop was to bring patients, charities and world-leading researchers from both academia and industry with PRPH2 biology and retinitis pigmentosa expertise together under one roof.  Approximately 120 people were in attendance, half being patients and their families and the other half investigators. A primary objective of the meeting was to help raise awareness of PRPH2 mutations and establish a community of patients affected by them, a group of which already meets online every second month. Other important aims were to facilitate the sharing of knowledge and experiences, understand and join up the current research landscape, and identify key gaps and identify the steps needed to address them. The event was incredibly successful in bringing researchers together and led to the forging of new collaborations, having even already led to the publication of new science.

By pure coincidence, the 3D molecular structure of the PRPH2 protein was elucidated in November 2022 by an academic research group from the Netherlands and, being a scientist and an expert in protein structures myself, I was invited to explain their results to the audience. This gave me the wonderful opportunity to explain how mutations in proteins can give rise to genetic diseases and specifically to the one that brought us all together in La Jolla on this occasion.  This was an amazing experience and it also allowed my family to enjoy a great holiday at the end.

A crucial outcome of the meeting was that we will all meet again in the next few years to discuss progress in the research that the Nixon Foundation with the Foundation for Fighting Blindness have decided to support following the huge success of the workshop – an incredibly happy outcome which gives us all more hope in the difficult fight against RP.

I had limited expectations of what genetic testing for RP might achieve but I am astounded by what unfolded. A few years later I have access to a large and expanding network of fellow patients, friends and scientists, along with far greater hope for what the future may bring than what I started with.

Retina UK is keen to facilitate treatments for everyone living with inherited sight loss. With around 300 causative genes, this is a challenge. However, in-depth research on one particular gene can generate findings and resources that can be useful in other cases, and we will encourage the researchers we fund to consider how the outcomes of their work can be more broadly applied.

In addition, many research groups are investigating potential therapies that could work regardless of the underlying genetic fault, so could be relevant for large proportions of the Retina UK community. For example, we are currently funding a project to investigate an “off the shelf” stem cell treatment.

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