The Visionaries: Sight for sore eyes

The eye has been a focus for several companies and academics to realise the potential of stem cell therapy. As the eye is immunoprivileged there is less chance of rejection or immune response. Also, end outcome is easier to access, and if required the cells can be directly observed at site of transplantation
The Institute of Opthalmology (IoO), UCL is at the forefront of most of developments with pioneering research, moving forward basic science into clinical trials.
Currently there are 2 clinical trials being undertaken in the UK in opthalmology using cell ular therapy: At Newcastle University using ex-vivo expanded limbal stem cells, and Advanced Cell Technology using Retinal pigmented epithelial (RPE) cells for Stargardt's disease at Moorfields Eye Hospital and Princess Alexandra Eye Pavillion, Edinburgh

Professor Francisco Figueiredo at Newcastle University is leading a Phase II clinical trial using Autologous limbal stem cells for unilateral limbal stem cell deficiency. The trial involves taking limbal stem cells from the patients healthy eye, which are then grown on an amniotic membrane expanded ex vivo and transplanted onto the eye. This can be used to treat patients who have had damage to their eye by acid/alkali that is very painful. Results from their first trial, showed significant decrease in pain in every patient and improvement in eye sight. The GMP manufacture for the current clinical trial is undertaken at the Newcastle Bioscience Cellular Therapy Facility. Look at this presentation for more details of the IMP manufacture.

Other research targeted towards treating similar indications, involves Professor Julie Daniels, Institute of Opthalmogy, and her team, in partnership with TAP Biosystems, for development of a biomimetic cornea. This has developed with the RAFT (real architecture for 3D tissues) production technology which creates a natural collagen scaffold that can replicate features of the stem cell niche and deliver a corneal tissue equivalent. This is still at the pre-clinical trial stage. Professor Daniels has already treated 25 patients so far for corneal damage (see here)

Advanced Cell Technology are undertaking a phase I/II clinical trial at Moorfields Eye Hospital with RPE cells generated from human embryonic stem cells in patients with Stargardt's disease. These cells are injected into the sub-retina of the eye in suspension. This is a safety and tolerability study using increasing doses (number of cells). Secondary outcome measures will assess cell engraftment.

Similar to the ACT trial, Pete Coffey, of Institute of Opthalmogy, UCL, is working in collaboration with Pfizer Neusentis to develop RPE cells derived from hECSs delivered a membrane for patients with age related macular degeneration (AMD). By transplanting the cells on a membrane they are hoping to overcome inherent problems observed with the majority of all stem cell therapies, engraftment. This is also particularly relevant to the disease state as for AMD the bruch's membrane is damaged. With a backing of a major pharma, the first of it's kind in stem cell therapy, has huge implications with many content to sit on the sidelines and watch out any developments.

Further down the line is Professor Robin Ali, and his team at IoO/UCL, producing photoreceptor cells generated from embryonic stem cells. The research is very early stage, with many challenges in the mouse model still to be overcome before this can move forward into man. By utilising a 3D culture method they are able to mimic normal development and pick and purify the cells at the right stage to increase successful transplantations. A very exciting and important milestone towards curing blindness.

References & Links

Gonzalez-Cordero et al. Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina. Nature biotech. 2013

Kolli et al, Successful clinical implementation of corneal epithelial stem cell therapy for treatment of unilateral limbal stem cell deficiency  2010 Mar 31;28(3):597-610

Levis et al. Plastic Compressed Collagen as a Novel Carrier for Expanded Human Corneal Endothelial Cells for Transplantation Plastic Compressed Collagen as a Novel Carrier for Expanded Human Corneal Endothelial Cells for Transplantation. PLoS ONE 7(11)

London project to cure blindness

Schwartz, et al Embryonic stem cell trials for macular degeneration: a preliminary report Lancet, 379 (2012), pp. 713–720

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