Towards co-transplantation approaches to treat retinal degeneration: application of degradable hydrogels
Brief plain language background
Cell replacement therapy offers a promising approach for the treatment of advanced retinal disease. For many IRDs, this requires transplantation of photoreceptors alone, but in AMD, photoreceptors and RPE would likely need to be replaced. We have been at the forefront of photoreceptor replacement therapy since its inception; we have established protocols for the manufacture of clinical-grade human stem cell-derived cone photoreceptors that can restore visual function following transplantation into mouse models of end-stage retinal degeneration and are moving toward clinical trials for cone transplantation. Co-transplantation presents new surgical challenges around cell reflux and cell organisation so, working with collaborators in Oxford, we have developed biomaterials that support RPE sheet transplantation and identified a candidate hydrogel (details withheld) that aids photoreceptoronly transplantation, with the overarching aim of developing a photoreceptor/RPE co-transplantation approach.
This project tests whether hydrogel encapsulation can enable targeted photoreceptor delivery for maximum treatment effect.
What problem/knowledge gap does it help address
Photoreceptor replacement therapy offers a potentially disease agnostic treatment for reversing sight-loss and is now moving rapidly towards the clinic with a trial soon starting in the USA, and we expect to begin one in the UK within the next 18months. Looking ahead, more complex diseases like AMD may require replacement of both RPE and photoreceptors, bringing new levels of surgical complexity to achieve appropriate cell distribution and organisation within the grafted area, along with minimal reflux. This project seeks to carefully model and mitigate some of the surgical challenges around photoreceptor transplantation by employing hydrogel encapsulation to support targeted placement of donor photoreceptors with/without accompanying RPE, thereby establishing key parameters for progressing treatment development for retinal dystrophies encompassing RPE damage.
Aim of the project
To determine if and how donor photoreceptor encapsulation using biodegradable hydrogels improves cone photoreceptor transplantation outcome and whether this can be used to support photoreceptor/RPE co-transplantation approaches.
Potential impact on people with sight loss
This project directly supports work towards developing an effective cell replacement treatment for advanced retinal degeneration. In the first instance, the team seek to transplant single-cell suspensions of cones, but the subsequent aim will be to combine this with RPE sheet co-transplantation. It is conceivable that early results from this project may inform the first clinical trial that is already in development (within 2 yrs) but will undoubtedly directly contribute to any follow-up cone-only trials and photoreceptor/RPE co-transplantation approaches (within 5 yrs).