Inside out: regenerative medicine for recessive dystrophic epidermolysis bullosa

Abstract

Epidermolysis bullosa is classified as a genodermatosis, an inherited genetic skin disorder that results in severe, chronic skin blistering with painful and life-threatening complications. Although there is currently no cure for epidermolysis bullosa, concurrent advances in gene and stem cell therapies are converging toward combinatorial therapies that hold the promise of clinically meaningful and lifelong improvement. Recent studies using hematopoietic stem cells and mesenchymal stromal/stem cells to treat epidermolysis bullosa have demonstrated the potential for sustained, effective management of the most severe cases. Furthermore, advances in the use of gene therapy and gene-editing techniques, coupled with the development of induced pluripotent stem cells from patients with epidermolysis bullosa, allow for autologous therapies derived from a renewable population of cells that are patient-specific. Here we describe emerging treatments for epidermolysis bullosa and other genodermatoses, along with a discussion of their benefits and limitations as effective therapies.

Profiling Immune Expression to Consider Repurposing Therapeutics for the Ichthyoses

“…For disorders in which the mutation reduces gene and protein expression, progress has been made through introducing the normal gene and expanding corrected cells for skin transplantation for life-threatening junctional (Hirsch et al, 2017;Mavilio et al, 2006) and dystrophic forms (Siprashvili et al, 2016) of epidermolysis bullosa. Furthermore, the ability to introduce corrected genes into stem cells promises to both improve transplantation of corrected cells and potentially direct introduction systemically to reach target sites (Vanden Oever et al, 2018). Newer technology using gene editing has yet to reach human trials for skin disease, but it is showing great potential in vitro and in early animal models.…”

Thymosin β4: potential to treat epidermolysis bullosa and other severe dermal injuries

“…There is an urgent need to find an effective treatment for EB patients. A variety of current clinical studies are focusing on gene and/or cell therapy as well as on either topical or systemic drug treatments [18][19][20][21][22][23] (clinicaltrials.gov) (table 1). Such studies are progressing and offer hope for the patients.…”

“…Some gene therapy approaches have used or will use intradermal injections of genetically modified autologous fibroblasts (FCX-007), intravenous infusion of genetically modified stem cells (IMP-allo-APZ2-EB), topical gene therapy (KB103), viral transfer of the collagen VII gene to keratinocyte sheets (LZRSE-Col7A1), autologous genetically modified epidermal cells as grafts, and genetically corrected epidermal autografts (ATMP). Cellbased therapy using autologous stem cells is progressing in the clinic with several sites starting trials for EB patients using either adipose stem cells or mesenchymal stromal cells [18,20,21]. The expected development time for gene and/or cell therapy and potential high cost suggest that these approaches may not be available soon or to all patients.…”

Genodermatozy – patogeneza i diagnostyka molekularna

“…Dlatego też każdorazowo badanie genetyczne powinno obejmować nie tylko chorego, ale również jego rodziców. Dodatkowym elementem, który w erze terapii spersonalizowanych zaczyna mieć coraz większe znaczenie, jest również możliwość zaproponowania pacjentowi specjalistycznego programu leczniczego zindywidualizowanego w zależności od rodzaju uszkodzonego genu lub występowania określonych mutacji [40,45,46].…”