Gene Therapy for Congenital Adrenal Hyperplasia
What is congenital adrenal hyperplasia?
Congenital adrenal hyperplasia (CAH) is a genetic disorder of the adrenal glands that causes a deficiency of or overabundance of three types of hormones: cortisol (which regulates energy, blood pressure and blood sugar and helps us recover from a sudden illness) aldosterone (which governs the amount of salt and water in the body) androgens (which control the development of male characteristics)
These hormone imbalances can lead to serious illness, atypical genitalia, early puberty, growth concerns and other problems.
How is gene therapy used to treat congenital adrenal hyperplasia?
Children with classic congenital adrenal hyperplasia have mutations in the CYP21A2 gene. This causes a deficiency of 21-hydroxylase, an enzyme essential for making cortisol and aldosterone.
Gene therapy for classic CAH uses a viral vector to deliver functional copies of the CYP21A2 gene, so the adrenal glands can properly make 21-hydroxylase. This restores the ability to make cortisol and aldosterone. The gene therapy is delivered in one intravenous (IV) dose.
Participants in the clinical trial will be followed for five years.
The ultimate goal of the gene therapy is to restore the adrenal glands’ normal function: responding to the body’s natural signals by releasing the right amount of hormones to react to stress, illness and daily living without additional medication.
CAH treatment options at CHOP
Currently, individuals with CAH must take daily medication to replace missing hormones and take “stress doses” if they are ill or injured to prevent life-threatening events called adrenal crises. Lifelong treatment is required.
Children with CAH are followed by experienced clinicians in CHOP’s Congenital Adrenal Hyperplasia Program, which is part of the Adrenal and Puberty Center. Each child receives an individualized care plan, and parents and caregivers are trained in how to administer daily medications, watch for symptoms of an adrenal crisis and treat any crises.
Clinical trials for CAH
Children’s Hospital of Philadelphia is a site of a clinical study for a gene therapy called AAV BBP-631 from Adrenas Therapeutics, a subsidiary of BridgeBio. This study is designed to evaluate the safety, tolerability and efficacy of AAV5-based BBP-631 in individuals 18 years and older who have been diagnosed with classic congenital adrenal hyperplasia.
If AAV BBP-631 is shown to be safe and effective in adults, a clinical trial for younger patients with classic CAH is planned.