Induced pluripotent stem cells (IPSC) were a big advance in stem technology in 2007, being able to take skin cells from a person and make stem cells was amazing for us as research scientists. We were sent some of the first IPSC created and, in 2009, published our first paper showing that we could make RPE from iPSC.

The benefit of using IPSC meant we could take a cell from a patient with inherited disease, and make that same diseased cell in a dish. Ultimately this means we can use the cells to find out more about the disease, the early mechanisms, and work out ways of fixing the disease in the cells. So, in 2011 I went to Boston to learn how to make IPSCs and brought that method back to London. We then established an iPSC bank, as a resource for researchers working on eye disease. We have over 40 cell lines from patients with various inherited retinal dystrophies in that bank, including yours.

I was interested in using iPSC to understand RPE disease. At the time, Best disease was one of those RPE diseases that we didn’t know much about, so I started working with Tony Moore and Andrew Webster, and recruited patients with Bestrophinopathies (Best disease, ADVIRC and ARB). I then applied for a project grant from the Macular Society to fund this work, and in 2015 I received my first independent funding which allowed me to start my research on Bestrophinopathies. The initial project was to find out more about the disease, what happens to BEST1 in patients and why mutations in this gene cause such a variety of issues and various diseases. We’re now working on testing CRISPR (clustered regularly interspaced short palindromic repeats), genome editing, as a therapy for the dominant bestrophinopathies, Best Disease and ADVIRC, again I applied to the Macular Society for funding, and received another grant, which started in 2018.

Your cells are being used in the second project. We’ve been able to make RPE from your cells and we found that the BEST1 protein is not expressed in the correct place in the RPE cell. We are now using CRISPR editing to switch off the faulty copy of the gene in your cells. Before lockdown we managed to cut out some of your faulty BEST1 gene using CRISPR, we think this is enough to switch off that faulty copy. So we’re now just waiting to start back in the labs so that we can see what has happened to the cells, hopefully getting rid of the bad copy of BEST1 will mean that the healthy copy will go to the right place in the cell and do its job there.

The project would not have been possible without funding from the Macular Society, so they have been instrumental in driving this project forward. We plan to test the CRISPR editing approach in other patient cells to take this forward as a therapy, essentially performing a clinical trial in a dish, to make sure it works before taking it anywhere near patients.

In terms of how much is needed for the research into Bestrophinopathies- it’s like the old question, how long is a piece of string? I received two project grants from the Macular Society, each for £170,000. So £340,000 has paid for 5 years of research into the disease. We would need to raise further funding to take this forward as a therapy.

Further details about research into Bestrophinopathies and potential therapies can be found here https://www.ucl.ac.uk/ioo/research/research-labs-and-groups/carr-lab/bestrophinopathies-resource-pages/research/research.