Developing an Investigational Gene Therapy for Congenital Adrenal Hyperplasia
Pre-screening for the ADventure Trial for Adult CAH has begun! Click the ADventure Trial button for more information about the trial, or read below for more information about Adrenas and the ADvance-CAH gene therapy program.ADventure Trial
ABOUT CLASSIC CONGENITAL ADRENAL HYPERPLASIA
Congenital adrenal hyperplasia (CAH) is a group of genetic disorders that affect the adrenal glands, which produce hormones that help regulate the body’s metabolism and stress response. Adrenas Therapeutics is developing an investigational gene therapy for classic CAH due to 21-hydroxylasedeficiency, which is the most common cause of CAH.
Classic CAH due to 21-hydroxylase deficiency involves mutations in the CYP21A2 gene that is essential for making the hormones cortisol and aldosterone. People with a non-working CYP21A2 gene have hormonal imbalances that cause metabolic issues as well as problems related to excess accumulation of androgens. This accumulation along with the underlying inability to produce sufficient cortisol and/or aldosterone can lead to acute, life-threatening events called adrenal crisis.
There are two forms of classic CAH for which Adrenas is developing its investigational gene therapy:
- Salt-wasting classic CAH - People living with this type of CAH cannot produce enough cortisol and aldosterone (which helps maintain normal fluid volume and blood pressure in the body, along with proper levels of sodium and potassium).
- Simple-virilizing classic CAH - People living with this type of CAH can produce some aldosterone but cannot make enough cortisol.
INVESTIGATIONAL GENE THERAPY FOR CLASSIC CAH
Medicines such as steroids are available to help treat classic CAH, however even with careful medication management, adults and children living with CAH are at higher risk for life-threatening adrenal crisis caused by low levels of cortisol and/or aldosterone. Some studies have even shown that CAH can be associated with a shortened lifespan. Lifelong steroid treatment can have significant side effects, including metabolic and bone disease, obesity, psychiatric effects, and effects on the cardiovascular and immune systems. These treatments often fail to control excess hormone (androgen) levels, leaving people with unmanaged symptoms that can impact fertility, decrease quality of life, and the resulting abnormal daily rhythm of hormone production can also lead to fatigue and sleep problems.
Gene therapy is an approach for treating genetic diseases such as CAH. The Adrenas investigational gene therapy is designed to use an AAV5 vector to deliver a functioning copy of the CYP21A2 gene, which provides instructions for making an enzyme called 21-hydroxylase. Through the addition of a functioning CYP21A2 gene, the Adrenas investigational gene therapy approach has the potential to offer something that no other treatment for CAH can offer: it may enable a person living with CAH to produce cortisol and aldosterone in response to the body’s rhythms, stress levels and the demands of daily living. If successful, this may allow people living with CAH to reduce their steroid doses or even eventually allow them to stop taking steroids entirely. The Adrenas investigational gene therapy will be administered in one intravenous (IV) dose.
ADVANCE-CAH GENE THERAPY PROGRAM OVERVIEW
Adrenas’ goal is to provide a safe and effective gene therapy treatment for adults and children living with classic CAH through the ADvance-CAH gene therapy program. The first stage of the Adrenas program is a clinical trial to evaluate the safety and tolerability of the investigational gene therapy in adults with classic CAH, as well as to identify an optimal dose range for future studies. This clinical trial is called the ADventure Trial, click here for more information on the trial and potential participation.
We will initiate clinical studies in children when sufficient data have been collected and analyzed from adult clinical trial participants. In comparison to adults with CAH, children with CAH represent a unique population with distinct developmental and physiological differences, and Adrenas recognizes the critical need for pediatric patients with CAH to have alternatives to the current treatment options.
The Adrenas gene therapy approach is based on research by Pierre F. Bougneres, MD, PhD, a pediatric endocrinologist at University Hospitals of Paris-Sud Bicêtre. Dr. Bougneres has treated patients with endocrine diseases such as CAH for over 30 years and conducted research that showed it was possible to safely modify CAH phenotypes in an animal model that mimics the human disease. Dr. Guangping Gao, PhD, is an important advisor to Adrenas Therapeutics. Dr. Gao, a pioneer in adeno-associated virus (AAV) gene therapy and leader of the Horae Gene Therapy Center at the University of Massachusetts Medical School, has developed several novel approaches for treating people with gene therapy using different AAV vectors.
Evidence from testing the Adrenas investigational gene therapy for classic CAH in an animal model of CAH due to 21-hydroxylase deficiency has shown that an AAV5 gene therapy approach resulted in correction or modification of hormonal imbalances associated with the condition. Other studies in animals have also shown that the gene therapy remains active in the adrenal gland of animals over months (the entire length of the animal study), supporting the idea that this therapy could have a lasting effect in people living with CAH. Studying gene therapy in these animal models is an important step before moving to clinical trials in people living with CAH. The AAV5 serotype Adrenas is using for its investigational gene therapy approach is also being studied in other rare disease gene therapy clinical trials.
Information and support are available for families affected by CAH from advocacy organizations such as:
Families can also access resources on gene therapy, endocrinology, drug development and understanding clinical trials by visiting:
- American Society of Gene & Cell Therapy
- Endocrine Society
- European Society for Pediatric Endocrinology
- European Society of Gene and Cell Therapy
- Hormone Health Network
- Pediatric Endocrine Society
Adrenas Presentations and Posters
2019 European Society of Gene & Cell Therapy Poster
2021 Endocrine Society Annual Meeting Poster
Gene Therapy Webinar (June 2020)
Adrenas Therapeutics, a subsidiary of BridgeBio Pharma, is a biotechnology company focused on developing a treatment for CAH caused by a mutation in 21-hydroxylase. Adrenas is led by a team of experienced biotechnology executives. Together with people living with CAH and physicians, the company aims to develop a safe and effective gene therapy treatment for CAH.
For specific questions related to the Adrenas clinical program, please email: email@example.com