Letter to the Editor: “Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline”

The Journal of Clinical Endocrinology & Metabolism recently published an Endocrine Society Clinical Practice Guideline for congenital adrenal hyperplasia (CAH) by Speiser et al. (1). The authors listed works by Tajima et al. (2) and Ruiz-Babot et al. (3) as preclinical research in gene therapy for 21-hydroxylase deficiency. These studies have undoubtedly opened the door to new therapeutic approaches to CAH. However, they have some limitations in terms of the clinical applicability of their findings. Tajima et al. (2) used an adenovirus vector, which can induce only a transient expression. Although the lentivirus vector used by Ruiz-Babot et al. (3) can produce long-term expression, the vector is integrated into genomic DNA and therefore may be associated with tumor genesis.

We published another approach in 2016 (4). In our study, we performed adeno-associated virus (AAV)-mediated transfer of the cytochrome P450 21-hydroxylase gene into the muscle tissue of 21-hydroxylase-deficient mice, inducing long-term expression without genomic integration (5). Indeed, multiple clinical trials for other congenital disorders, such as lipoprotein lipase deficiency (6) and aromatic l-amino acid decarboxylase deficiency (7), demonstrated the clinical effectiveness and safety of AAV-mediated gene transfer. Moreover, gene transfer into muscle tissue might be less invasive than direct adrenal induction by laparoscopy or catheterization in clinical practice. We demonstrated that an intramuscular injection was effective enough to ameliorate clinical severity throughout the life of 21-hydroxylase-deficent mice (4). Therefore, we propose that AAV-mediated transfer of cytochrome P450 21-hydroxylase into muscle tissue be considered as a potential approach in gene therapy for CAH.

Acknowledgments

Financial Support: This work is supported by a Grant-in-Aid for Scientific Research (C) (22591148, 25461575, 16K10005) from the Japan Society for the Promotion of Science.

Disclosure Summary: The authors have nothing to disclose.

Abbreviations:

Abbreviations:
 
• AAV

  adeno-associated virus

 
• CAH

  congenital adrenal hyperplasia

References