Treatment of Hereditary Epidermolysis Bullosa: Updates and Future Prospects

Chao-Kai Hsu; Sheng-Pei Wang; Julia Yu-Yun Lee; John A. McGrath

Disclosures

Am J Clin Dermatol. 2014;15(1):1-6. 

In This Article

6 Bone Marrow Stem Cell Therapy

Bone marrow transplantation (BMT) is primarily indicated for hematological diseases, such as aplastic anemia and leukemia. However, because the pluripotent stem cells can differentiate into not only blood cells but also other functional cells, the scope of BMT has been expanded to encompass tissue regeneration and thereby treat genetic disorders. In 2010, a phase I clinical trial of whole BMT in six children with RDEB was reported.[25] Those transplants mostly involved myeloablation of the RDEB subjects' bone marrow followed by sibling-matched donor grafting. Decreased skin blistering (by up to 50 % in half; more than 50 % in the remainder) was noted and there was increased C7 in the skin of five of six subjects. Clinical improvement was also noted in the one individual who did not show an increase in C7; some children are now more than 5 years post-BMT and their skin remains much improved (unpublished data; personal communication, Dr J. Tolar, September 2013). One of the children reported in the trial died from graft failure and sepsis and a further child died from complications of the RDEB before grafting took place. Subsequently, new protocols for the use of BMT in RDEB patients have started to be developed— usually involving revisions to the immune-conditioning regimens and transplantation protocols (personal communication, Dr J. Tolar). Reduced intensity conditioning has significantly reduced the mortality of BMT in RDEB although substantial clinical improvement still occurs. Several patients have reported a reduction in blister severity from ~70 % of their skin surface to ~5 %, although none has been totally cured. The mechanism of action leading to the clinical and skin pathology improvement remains unclear since some patients continue to benefit long-term despite showing no increase in skin C7, especially in those who have undergone reduced intensity conditioning BMT. The optimal use and application of BMT in RDEB (and potentially in other forms of EB), therefore, remains in clinical development.

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