# Study of the Safety, Tolerability, and Efficacy of an iPS Cell-based Therapy for Recessive Dystrophic Epidermolysis Bullosa Delivered with a Spray on Skin Device

> **NIH NIH UG3** · UNIVERSITY OF COLORADO DENVER · 2023 · $538,200

## Abstract

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic disorder characterized by fragility
of the skin and mucous membranes. Affected individuals are born with open wounds and blisters which
become recurrent and/or chronic over time. Both the skin and mucosal epithelia heal with scarring, causing
fusion of the fingers and toes (pseudosyndactyly) and joint contractures, microstomia, and esophageal
strictures. Non-skin complications include failure to thrive, anemia, and osteopenia/osteoporosis. The course of
RDEB is unremitting, and patients surviving into adulthood have a high risk of developing aggressive
squamous cell carcinomas that can be fatal. Shortened life-expectancy is the norm for patients with
RDEB. There is no approved disease-modifying treatment for RDEB. Current therapies are palliative and focus
on promoting wound healing, nutritional support, and treating complications as early as possible.
 RDEB is caused by mutations in COL7A1, leading to absence or deficiency of functional collagen VII
(Col7), an integral component in the adhesion of epithelia to dermis in the skin and mucous membranes.
Remission from the open wounds of RDEB could be obtained if functional Col7 is replaced in the
skin. However, a durable remission can only be attained if an affected patient’s cells are genetically
corrected, and a sufficient number of renewable cells engraft back into wounds. This pilot, phase 1 study will
evaluate the safety and efficacy of one such approach in patients with RDEB who have the common
mutation c.7485+5G>A. Using an ex vivo approach, the patient’s skin cells will be genetically corrected and
reprogrammed into induced pluripotent stem cells (iPSCs) in an efficient one step process. The iPSCs will be
differentiated into functional keratinocytes and fibroblasts expressing Col7. These keratinocytes and fibroblasts
will be transplanted to the patient using a novel Spray-on-Skin device developed by AVITA Medical.
 The primary objective of this study is to evaluate the safety of this treatment approach. After treatment,
patients will be monitored for 1 year for the development of squamous cell carcinoma or teratomas within the
treated areas, immune reactions, and other adverse events. The secondary objectives are to provide proof-of-
concept data that the use of genetically corrected iPSC-derived keratinocytes and fibroblasts will function
normally and are an effective treatment for chronic wounds in patients with RDEB. The expression of Col7 and
formation of anchoring fibrils after treatment will be evaluated. In addition, wound closure and the durability of
wound closure compared to standard wound care will be studied. We hypothesize that this treatment will be
safe and well-tolerated and lead to the regeneration of histologically normal skin expressing Col7 that is not
prone to re-wounding. If successful, this work will lay the foundation for the development of iPSC-based
therapies for other monogenic diseases affecting ...

## Key facts

- **NIH application ID:** 10721324
- **Project number:** 1UG3AR082887-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Anna Lee Bruckner
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $538,200
- **Award type:** 1
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10721324

## Citation

> US National Institutes of Health, RePORTER application 10721324, Study of the Safety, Tolerability, and Efficacy of an iPS Cell-based Therapy for Recessive Dystrophic Epidermolysis Bullosa Delivered with a Spray on Skin Device (1UG3AR082887-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10721324. Licensed CC0.

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