Where is Pex1 normally expressed in the mouse retina (e.g. what cell types)?
PEX1 is concentrated at the inner segment and outer plexiform layer in both mouse and
human retina.
Why did you choose subretinal vector delivery in the mouse model?
We selected subretinal delivery to best access our target cells – the outer retina, where
the retinal phenotype originates in this model.
What about side effects (cataract, etc.)? In the mouse model, how long did it take for the
retina to re-attach after injection?
There were no detectable structural or functional side effects post-injection. The retina
had re-attached when it was visualized histologically 2 months post-injection.
Given the limited data on the natural history of PEX-associated retinopathy – do you plan
deep phenotyping studies? For how long?
Yes. We have completed and published a retrospective analysis of vision in a large ZSD
cohort as part of a retrospective natural history study. We recently launched a funded
longitudinal prospective natural history study assessing retinal pathology and functional
vision in participants of various ages (clinicaltrials.gov NCT06190626). This study will
identify the optimal treatment window and clinical outcomes for this population.
Assessments will be performed yearly for 5 years, but we expect informative results even
after the first tests.
Do you observe any structural protection of photoreceptors and bipolar cells in addition to
the functional improvements in the gene therapy-treated mutant mice?
Yes. We have seen striking improvements in photoreceptor and RPE structure in our more
recent studies.