Limbal stem-cell therapy for RDEB

Contents:

Limbal stem cells for treatment of corneal wounds in Epidermolysis Bullosa

Investigator: Professor Jakub Tolar, Professor of Paediatrics

Institution: Department of Paediatrics, University of Minnesota, USA

Grant: Commissioned and funded by The Sohana Research Fund - $250,000 Completed

Lay summary

Corneal damage in RDEB patients results in great discomfort and in reduced quality and loss of vision. For those affected, this remains one of the least treatable problems of RDEB disease. As blood and marrow transplantation does not correct cells in the eye—leaving patients still vulnerable to painful corneal abrasions—we want to develop an alternative treatment that creates genetically corrected cells for use directly in the eye.

RDEB and other genetic diseases are caused by “typos” (mutations) in the DNA in our cells. DNA is “written” with four unique “letters” (molecules) in various combinations and in strings as long 3.2 billion of these letters in an exact, specific order. Alteration to as little as one of these letters can cause a genetic disease like RDEB.

We plan to take a small corneal biopsy from a patient and use a form of gene surgery on these cells to permanently correct the “typos” that cause a lack of type VII collagen production. We have a technology that can cut the DNA in an exact location, remove the error, and carefully and specifically replace the normal order of letters.

With the typo permanently corrected in these cells, we hope to give them back to the patient. The corrected cells will then produce the missing type VII collagen and the corneal damage will not continue. We have already successfully performed this gene surgery in our laboratory to correct skin cells.

We are optimistic that we can generate gene-corrected corneal cells that could greatly improve the lives of people with RDEB, whose only options today are supportive care and resilience.

Changes in future research.

The last 10 years of RDEB research have been revolutionary. Therapies like gene therapy and protein therapy are now physically possible, and the first trials in cellular therapy (local injection of fibroblasts and mesenchymal stromal cells, systemic infusion of mesenchymal stromal cells, and long-term systemic therapy by blood and marrow transplantation) are well underway and under constant improvement.

Our research team has always been guided, motivated and inspired by people with RDEB and their families. Throughout the hundred-year history of this disease, they have coped with insurmountable obstacles and continued to be resilient. With this kind of need, we know they have waited long enough. We see our work as part of global effort to cure RDEB, an effort that is seeing new kinds of success and will build on the discoveries of the past 10 years.

What is important about this research?

“We know that what EB patients and families want is a cure. DEBRA funding is helping us make advances that will lead to improved therapies and hopefully, a cure.”

Dr Jakub Tolar Dr Jakub Tolar is the Director of the Stem Cell Institute and a Professor at the University of Minnesota. His research led to the first use of bone marrow transplant as a therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB). He is now developing new treatments using cells from the RDEB patients themselves. He is exploring both naturally occurring, self-corrected cells and gene-edited cells as protein-producing sources for skin wounds and for whole-body therapy. Dr Tolar and his team are working hard to move these ideas from the laboratory to the clinic.