Rare Disease Report

Gene Therapy Helps Wound Healing in Rare Skin Disease

NOVEMBER 02, 2016
James Radke, PhD
Gene therapy to treat epidermolysis bullosa is showing great promise. This week in JAMA, Soprashvili et al report on their phase 1 clinical trial showing genetically corrected skin grafts to be effective in the majority of grafts applied (24 grafts on 6 wounds in 4 patients).
Based on the results, a phase 2 study is currently underway by Abeona Therapeutics.

Phase 1 Study

This was a phase 1 clinical trial involving 4 patients with severe recessive dystrophic epidermolysis bullosa who had wounds suitable for grafting of at least 100 cm2. Patients with undetectable type VII collagen keratinocyte expression were excluded.
Skin cells from the 4 patients were transduced with good manufacturing practice–grade retrovirus carrying full-length human COL7A1 and assembled into epidermal sheet grafts. A total of 24 type VII collagen gene–corrected grafts (approximately 35 cm2) were transplanted onto 6 wounds in each of the patients.
The primary outcome measure was safety but type VII collagen expression and wound healing were also assessed at 3, 6, and 12 months after grafting.
The 4 male patients (mean age, 23 years [range, 18-32 years]) were all male with an estimated body surface area affected with recessive dystrophic epidermolysis bullosa of 4% to 30%.
All 24 grafts were well tolerated without serious adverse events.
Type VII collagen expression at the dermal-epidermal junction was demonstrated on the graft sites by immunofluorescence microscopy in 9 of 10 biopsy samples (90%) at 3 months, in 8 of 12 samples (66%) at 6 months, and in 5 of 12 samples (42%) at 12 months.
Wounds with recombinant type VII collagen graft sites displayed 75% or greater healing at 3 months (21 intact graft sites of 24 wound sites; 87%), 6 months (16/24; 67%), and 12 months (12/24; 50%) compared with baseline wound sites.
These results are extremely encouraging given that wound in these patients may go unhealed for months to years due to the inability of the skin to stay attached to the underlying dermis and can cover a large percentage of the body.
In a press release, Timothy J. Miller, PhD, President and CEO of Abeona Therapeutics said, "The clinical data demonstrate that EB-101 gene therapy corrected the underlying genetic deficit in RDEB (recessive dystrophic epidermolysis bullosa) patient wounds for months to over a year, and the wounds closed -- which is remarkable for a disease where the patient's skin can blister and erode every day."

About Epidermolysis Bullosa

Epidermolysis bullosa (aka 'the worst disease you've never heard of') is a group of devastating, life-threatening genetic skin disorders impacting children that is characterized by skin blisters and erosions all over the body. 
The most severe form, recessive dystrophic epidermolysis bullosa, is characterized by chronic skin blistering, open and painful wounds, joint contractures, esophageal strictures, pseudosyndactyly, corneal abrasions and a shortened life span. Patients with recessive dystrophic epidermolysis bullosa lack functional type VII collagen (C7) owing to mutations in the gene COL7A1 that encodes for C7 and is the main component of anchoring fibrils that attach the dermis to the epidermis.
Epidermolysis Bullosa patients suffer through intense pain throughout their lives, with no effective treatments available to reduce the severity of their symptoms.
A couple years ago, we talked with Robert Ryan who summed up the disease quite well in this clip below.



Siprashvili Z,  Nguyen NT,  Gorell ES, et al.  Safety and Wound Outcomes Following Genetically Corrected Autologous Epidermal Grafts in Patients With Recessive Dystrophic Epidermolysis Bullosa. JAMA. 2016;316:1808-1817. doi:10.1001/jama.2016.15588

Image courtesy wikimedia commons.

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