Patricia Biasutto, born and raised in Venezuela and now heading ProQR’s LCA research and development team in Leiden (The Netherlands), has multiple reasons for being optimistic. Obviously, as a biotech scientist looking for a treatment for LCA, she cannot confirm that there is a breakthrough. Not yet. “We have definitely found something. ProQR’s team has developed a molecule that shows promising results in laboratory tests. In collaboration with various academic centers we have made tremendous progress and in 2017 we will take development to the next phase: clinical trials.”
Change the lives of patients
In search for the one molecule that may change the lives of the 2,000 patients (see text box) that suffer from LCA10, Biasutto and her colleagues applied what she describes as “the amazing innovative retinal organoid model of ‘optic cups’.” She explains, in a short lecture: “Before we can test our molecule in patients we first need to find out whether it works.
For LCA10 we had no good models to test this in and you cannot just take an eye from a patient! We worked together with the University College London (UCL) that recently developed this amazing technique where you can take a bit of skin from an LCA10 patient and turn the cells into stem cells and basically grow retinas in the laboratory. We were one of the first companies to use this 3D organoid model and with it show that sepofarsen does exactly what we hoped it does in the closest representation of a patient’s retina.”
The key to patient benefit
In the laboratory, the team found confirmation that the sepofarsen molecule restores the RNA sequence of the CEP290 protein that has a very important role in keeping photo-receptor cells (rods and cones) alive in the retina. In LCA10 patients, this protein is not formed. Hence, the photo-receptor cells in the retina die and – with that – the ability to see. “Restoring production of this protein may be the key to keep the retinas intact and prevent blindness. The next, exciting step will be clinical testing in patients.” Until now, every one of these steps, every new test produces another ‘green light’. “Seeing the molecule perform well in the ‘optic cup’ model is truly exciting. It is the sensation that scientists, like me, flourish on”.
Patricia calls the process of becoming aware of the molecule’s potential “a very fulfilling experience” and “an amazing feeling”. “But as much as I celebrate it, the life-changing moment has yet to come. That will have to come when the molecule actually proves to be effective in a patient. We took the first step – or hurdle. There is a green light, but we need more of them.”