The steep uphill path leading to ex vivo gene therapy for genodermatoses

Abstract

Cell therapy, gene therapy and tissue engineering have the potential to revolutionize the field of regenerative medicine. In particular, gene therapy is understood as the therapeutical correction of mutated genes by addition of a correct copy of the gene or site-specific gene modifications. Gene correction of somatic stem cells sustaining renewing tissues is critical to ensure long-term clinical success of ex vivo gene therapy. To date, remarkable clinical outcomes arose from combined ex vivo cell and gene therapy of different genetic diseases, such as immunodeficiencies and genodermatoses. Despite the efforts of researchers around the world, only few of these advanced approaches has yet made it to routine therapy. In fact, gene therapy poses one of the greatest technical challenges in modern medicine, spanning safety and efficacy issues, regulatory constraints, registration and market access, all of which need to be addressed to make the therapy available to rare disease patients. In this review, we survey at some of the main challenges in the development of combined cell and gene therapy of genetic skin diseases.

Education for the translation of Advanced Therapy Medicinal Products

“…A therapy, once established and certified, should be available and regularly applied to patients who need it to be publicly valuable. In the last years, we are witnessing the withdrawal from the market of many ATMPs that were not profitable enough for the companies selling them ( 37 – 39 ). These therapies—associated with high production costs—aim to treat rare diseases with a limited number of patients who can be treated worldwide.…”

Cost and availability of novel cell and gene therapies

“…However, once a therapy is successfully out of this first, biomedical “valley of death” and approved for use, it frequently encounters a second, economic “valley of death” that prevents its use in patients. This problem needs a solution for medical, ethical and economic reasons; readers are also refereed to recent articles dealing with the same problem for haematopoietic diseases (Aiuti et al , 2022 ; Halley et al , 2022 ) or genodermatoses (Palamenghi et al , 2022 ).…”