A Ray of Hope: Adrenal Hyperplasia may Get a Cure Soon

Scientists have developed the first humanized mouse model for a rare hereditary condition.

For the first time, mice with a faulty human gene responsible for a rare genetic illness called congenital adrenal hyperplasia have been created.

The discovery, presented at the 25th European Congress of Endocrinology, could aid in the development of new medicines for those suffering from the most common kind of congenital adrenal hyperplasia.

Congenital Adrenal Hyperplasia: A Collection of Hereditary Diseases

Congenital adrenal hyperplasia (CAH) is a collection of hereditary diseases that affects approximately one in every 15,000 births.

Congenital Adrenal Hyperplasia (CAH) - Causes, Symptoms, Diagnosis and Treatment
Congenital adrenal hyperplasia (CAH), also known as adreno-genital syndrome, is an inherited genetic condition that affects the adrenal glands. CAH is caused by deficiency of enzymes needed for steroid hormone synthesis.

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Mimicking congenital adrenal hyperplasia in mice can open new pathways for its cure in humans.

Mutations in the CYP21A2 gene cause the adrenal glands - a pair of tiny organs placed atop the kidneys - to generate low levels of cortisol and excessive amounts of androgen hormones such as testosterone in the most common form, known as 21-hydroxylase deficiency.

This results in early puberty, girls with male appearance, and a variety of health complications. Currently, steroid hormone replacement therapy is used for treatment, but this may often have harmful side effects.

In this study, researchers from the University Hospital Carl Gustav Carus in Dresden, Germany, replaced the gene Cyp21a1 in mice with the human gene CYP21A2 carrying a mutation.

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They found that the genetically modified mice at 20 weeks had enlarged adrenal glands while expressing the human mutated gene.

In addition, similarly to the human disease, the mutation caused both male and female mice to have low levels of corticosterone – the main stress hormone in mice that is the equivalent to cortisol in humans – and other hormonal imbalances.

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Although animal models for congenital adrenal hyperplasia exist, this is the first to reproduce the human condition in mice and able to survive without any treatments ().

Mice Mimic Congenital Hyperplasia Symptoms; Paving way for Further Studies

“Our mice accurately mimic the symptoms seen in human patients,” said lead author Shamini Ramkumar Thirumalasetty. “For example, the female mutant mice also have issues with fertility, which we believe is most probably due to the hormonal imbalances triggered by congenital adrenal hyperplasia.”

This mouse model will now allow the team to study the mechanisms of the disease and find the most effective treatments.

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“Although novel treatments are being developed to minimize the side effects of steroid hormones, these drugs lack effective in vivo models for pre-clinical testing,” said Ms. Thirumalasetty. “Our mouse can serve as an excellent model to test novel drugs and treatment options for patients with congenital adrenal hyperplasia, such as stem cell therapies, and will facilitate the transition from basic research to the clinic.”

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