Dataset Information

Leading edge: emerging drug, cell, and gene therapies for junctional epidermolysis bullosa.

ABSTRACT:

Introduction

Junctional epidermolysis bullosa (JEB) is a rare inherited genetic disorder with limited treatments beyond palliative care. A major hallmark of JEB is skin blistering caused by functional loss or complete absence of major structural proteins of the skin. Impaired wound healing in patients with JEB gives rise to chronic cutaneous ulcers that require daily care. Wound care and infection control are the current standard of care for this patient population.

Areas covered

This review covers research and clinical implementation of emerging drug, cell, and gene therapies for JEB. Current clinical trials use topical drug delivery to manipulate the inflammation and re-epithelialization phases of wound healing or promote premature stop codon readthrough to accelerate chronic wound closure. Allogeneic cell therapies for JEB have been largely unsuccessful, with autologous skin grafting emerging as a reliable method of resolving the cutaneous manifestations of JEB. Genetic correction and transplant of autologous keratinocytes have demonstrated persistent amelioration of chronic wounds in a subset of patients.

Expert opinion

Emerging therapies address the cutaneous symptoms of JEB but are unable to attend to systemic manifestations of the disease. Investigations into the molecular mechanism(s) underpinning the failure of systemic allogeneic cell therapies are necessary to expand the range of effective JEB therapies.

SUBMITTER: Keith AR

PROVIDER: S-EPMC7392816 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Epidermolysis bullosa (EB) includes a group of rare skin diseases characterized by skin fragility with bullous formation in the skin, in response to minor mechanical injury, as well as varying degrees of involvement of the mucous membranes of the internal organs. EB is classified into simplex, junctional, dystrophic and mixed. The impact of the disease on patients is both physical and psychological, with the result that their quality of life is constantly affected. Unfortunately, there are still no approved treatments available to confront the disease, and treatment focuses on improving the symptoms with topical treatments to avoid complications and other infections. Stem cells are undifferentiated cells capable of producing, maintaining and replacing terminally differentiated cells and tissues. Stem cells can be isolated from embryonic or adult tissues, including skin, but are also produced by genetic reprogramming of differentiated cells. Preclinical and clinical research has recently greatly improved stem cell therapy, making it a promising treatment option for various diseases in which current medical treatments fail to cure, prevent progression, or alleviate symptoms. So far, stem cells from different sources, mainly hematopoietic and mesenchymal, autologous or heterologous have been used for the treatment of the most severe forms of the disease each one of them with some beneficial effects. However, the mechanisms through which stem cells exert their beneficial role are still unknown or incompletely understood and most importantly further research is required to evaluate the effectiveness and safety of these treatments. The transplantation of skin grafts to patients produced by gene-corrected autologous epidermal stem cells has been proved to be rather successful for the treatment of skin lesions in the long term in a limited number of patients. Nevertheless, these treatments do not address the internal epithelia-related complications manifested in patients with more severe forms.