Does fludarabine have a beneficial effect in recessive dystrophic epidermolysis bullosa?

Linked Article: Vanden Oever et al. Br J Dermatol 2021; 185:380-390. Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic disorder. Patients with RDEB experience severe painful blistering and skin fragility due to separation of two layers of the skin: the dermis and epidermis. This occurs because type VII collagen (C7) is deficient or absent in the skin. C7 is a major component responsible for tethering the epidermis to the dermis. The skin heals with disfiguring scarring, and patients are at risk of secondary infection and an aggressive form of squamous carcinoma, a type of skin cancer. There is currently no cure but there are encouraging results from some experimental treatments. One treatment is haematopoietic stem cell transplantion, where the engrafted cells appear to increase the amount of C7 (a process called deposition) over the long-term. Unfortunately, this treatment requires long term immunosuppression and this is particularly risky in patients with RDEB, who are prone to infections. The authors, based in Minneapolis, USA, explored whether any of the drugs used in chemotherapy treatment used before transplant might have an effect on C7 deposition. They found that fludarabine influences the production of C7 in affected cells in RDEB. They describe various mechanisms for this effect. They stress the need to determine how much the increased C7 deposition following haematopoietic stem cell transplantation is because of the engrafted cells, and how much is from the patient's own cells stimulated by drugs such as fludarabine. They caution that drugs may cause deposition of non-functional C7, which could be harmful. Unfortunately, fludarabine is generally too toxic to use in patients with RDEB, but there is the possibility of less toxic analogues that could have the same desirable effect on C7 deposition and have clinical benefit.