We thank Drs. Naiki and Fukami for their letter (1) concerning the Endocrine Society’s recently updated Clinical Practice Guideline for congenital adrenal hyperplasia (CAH) (2), and we regret overlooking their paper reporting the use of adeno-associated virus (AAV) for the experimental treatment of CAH in genetically engineered mice (3). A comprehensive review of gene therapy approaches to CAH was beyond the scope of the Practice Guidelines, but readers interested in this topic may note that the AAV vector used by Naiki et al. (3) targeted Cyp21a1 to muscle, whereas others have used another AAV vector to target green fluorescent protein directly to the mouse adrenal (4).
Genetic approaches to treating CAH are in their infancy and will require extensive additional research before human therapy may be considered. The committee drafting the Practice Guidelines considers oral hormonal replacement therapy to be safe and effective; hence, any genetic therapy will need to become routine in other disorders before it can be used in CAH.
Acknowledgments
Disclosure Summary: R.J.A. and W.L.M. are consultants for Adrenas Therapeutics, Inc. Other disclosures are listed in Appendix B (2).
Glossary
Abbreviations:
- AAV
adeno-associated virus
- CAH
congenital adrenal hyperplasia
References
- 1.Naiki Y, Fukami M. Letter to the Editor: “Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline.” J Clin Endocrinol Metab. 2019;104(6):1926–1927. [DOI] [PubMed] [Google Scholar]
- 2. Speiser PW, Arlt W, Auchus RJ, Baskin LS, Conway GS, Merke DP, Meyer-Bahlburg HFL, Miller WL, Murad MH, Oberfield SE, White PC. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(11):4043–4088. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Naiki Y, Miyado M, Horikawa R, Katsumata N, Onodera M, Pang S, Ogata T, Fukami M. Extra-adrenal induction of Cyp21a1 ameliorates systemic steroid metabolism in a mouse model of congenital adrenal hyperplasia. Endocr J. 2016;63(10):897–904. [DOI] [PubMed] [Google Scholar]
- 4. Perdomini M, Dos Santos C, Goumeaux C, Blouin V, Bougnères P. An AAVrh10-CAG-CYP21-HA vector allows persistent correction of 21-hydroxylase deficiency in a Cyp21-/- mouse model. Gene Ther. 2017;24(5):275–281. [DOI] [PubMed] [Google Scholar]