ESPE Yearbook of Paediatric Endocrinology

J Clin Endocrinol Metab. 2020; 105(9): 3103–3107.https://pubmed.ncbi.nlm.nih.gov/32629476/

In this narrative review, the authors discuss the potential role of novel regenerative therapies for the treatment of adrenal insufficiency, including gene therapy and cell replacement strategies. More specifically, the authors discuss the heterogeneity in adrenal function in patients with Addison disease, including numerous case reports of spontaneous remission. The authors cite recent studies showing that, shortly after the onset of Addison disease, residual adrenal function might be restored using B-lymphocyte-depleting immunotherapy and ACTH treatment. The rationale is that ACTH stimulates the differentiation of the persisting progenitor or stem cells, while B-cell depletion prevents destruction of the newly differentiated cells (1). Furthermore, the cell turnover of the adrenal cortex limits the time-span of the effectiveness of gene therapy (2). A more promising strategy is adrenal cell transplantation, which is potentially curative. Research foci in this strategy include alternative cell sources, novel biomaterials that have been developed to improve cell viability of engineered cells upon implantation, and cellular therapies based on pluripotent stem cells (3).

Finally, the authors discuss the potential use of adrenal cells as a source for regenerative therapies of nonadrenal neurodegenerative diseases. More specifically, chromaffin cells from the adrenal medulla have been considered as a potential source of dopamine producing cells to treat neurodegenerative conditions, such as Parkinson disease (4).

Reference: 1. Napier C, Gan EH, Mitchell AL, Gilligan LC, Rees DA, Moran C, Chatterjee K, Vaidya B, James RA, Mamoojee Y, Ashwell S, Arlt W, Pearce SHS. Residual Adrenal Function in Autoimmune Addison’s Disease-Effect of Dual Therapy with Rituximab and Depot Tetracosactide. J Clin Endocrinol Metab. 2020; 105(4): e1250–e1259.2. Markmann S, De BP, Reid J, Jose CL, Rosenberg JB, Leopold PL, Kaminsky SM, Sondhi D, Pagovich O, Crystal RG. Biology of the Adrenal Gland Cortex Obviates Effective Use of Adeno-Associated Virus Vectors to Treat Hereditary Adrenal Disorders. Hum Gene Ther. 2018; 29(4): 403–412.3. Steenblock C, Rubin de Celis MF, Delgadillo Silva LF, Pawolski V, Brennand A, Werdermann M, Berger I, Santambrogio A, Peitzsch M, Andoniadou CL, Schally AV, Bornstein SR. Isolation and characterization of adrenocortical progenitors involved in the adaptation to stress. Proc Natl Acad Sci U S A. 2018; 115(51):12997–13002.4. Boronat-Garcia A, Guerra-Crespo M, Drucker-Colin R. Historical perspective of cell transplantation in Parkinson’s disease. World J Transplant. 2017; 7(3): 179–192.