Congential Adrenal Hyperplasia

AN INVESTIGATIONAL NEW TREATMENT FOR CLASSICAL CONGENTIAL ADRENAL HYPERPLASIA (CAH)

Corticotropin-Releasing Factor (CRF) is a central nervous system-based, hypothalamic hormone that acts on specific CRF receptors to stimulate the release of adrenocorticotropin hormone (ACTH). The primary role of ACTH is the stimulation of synthesis and release of adrenal steroids including cortisol. Blockade of CRF receptors in the pituitary has been shown to decrease the release of ACTH and subsequently attenuate the production and release of adrenal steroids and potentially alleviate the symptoms associated with diseases ranging from endocrinology to psychiatry.

We have a strategic position in the CRF field through our intellectual property portfolio and relationship with experts in the neuropsychiatric field. We have patents covering two receptor subtypes termed CRF1 and CRF2, and we have pending patent applications on small molecule organic compounds modulating the CRF receptors.

Targeting CRF1 for the treatment of Classical CAH

Congenital Adrenal Hyperplasia. Classical CAH is a rare genetic disorder affecting 20,000-30,000 people in the United States. The condition results in an enzyme deficiency altering the production of adrenal steroids. Because of this deficiency, the adrenal glands have little to no cortisol biosynthesis resulting in a potentially life-threatening condition. If left untreated, classical CAH can result in salt wasting, dehydration and eventually death. Even with cortisol replacement, persistent elevation of ACTH from the pituitary gland results in excessive androgen levels leading to virilization of females including precocious puberty, menstrual irregularity, short stature, hirsutism, acne and fertility problems.

Corticosteroids are the current standard of care for classical CAH. They are used to both correct the endogenous cortisol deficiency and reduce the excessive ACTH levels and androgen excess. However, the dose and duration of steroid use required to suppress ACTH is well above the normal physiological level of cortisol; resulting in bone loss, growth impairment, and Cushing’s syndrome as common and serious side effects. Through modulation of CRF, we hope to lower ACTH levels in individuals with CAH. In doing so, the goal would be to reduce the amount of exogenous corticosteroid necessary for classical CAH patients.