Cortisol Modulation Therapeutic Platform
Hypercortisolism (Cushing Syndrome)
Cushing syndrome is a disorder that occurs when there is too much cortisol activity (hypercortisolism) over a long period of time. Cortisol is sometimes called the “stress hormone” because it helps your body respond to stress. Cortisol also helps maintain blood pressure, regulate blood sugar, reduce inflammation, and turn the food you eat into energy.
Cushing syndrome is caused by excessive cortisol-like medication, such as prednisone, or a tumor that either produces or results in the production of excessive cortisol by the adrenal glands.
Administration of a cortisol modulator decreases cortisol activity and reduces the symptoms of hypercortisolism.
Relacorilant Clinical Trial (GRACE)
Relacorilant Clinical Trial (GRADIENT)
Cancer
In cancers that express glucocorticoid receptors (GRs), such as pancreatic, ovarian, and breast cancers, cortisol suppresses programmed cell death (apoptosis). Chemotherapy is intended to provoke cell death. Medications that reduce cortisol’s activation of GR may make chemotherapy more effective.
Cortisol modulation may also aid the immune system in fighting cancer. A healthy body produces cancer cells, but the immune system destroys them. Cortisol suppresses the immune system. Modulating cortisol may counter this effect, allowing the immune system to better identify and eradicate tumor cells.
Androgen hormones are the predominant stimulators of growth in tumors of the prostate. Patients treated with an androgen receptor modulator develop colonies of cells in which cortisol becomes the tumor’s growth factor. Combining a cortisol antagonist with an androgen receptor modulator may block this cancer escape route
Relacorilant + Nab-paclitaxel Clinical Trial
CORT125281 + Enzalutamide Clinical Trial
Relacorilant + Enzalutamide Clinical Trial
Mifepristone + Pembrolizumab Clinical Trial
Antipsychotic-Induced Weight Gain
Atypical antipsychotic drugs form the basis of therapy for patients with various psychiatric diseases, including schizophrenia and bipolar disorder. Unfortunately, these medications often cause rapid and significant weight gain along with insulin resistance, leading to type 2 diabetes mellitus and hypertension. Reducing cortisol activity reduces insulin resistance, and may ameliorate weight gain and its consequences in patients taking antipsychotic medications.
Miricorilant Clinical Trial
Nonalcoholic Steatohepatitis (NASH)
Nonalcoholic fatty liver disease (NAFLD) is defined by excessive fat (steatosis) in the liver and can progress to NASH, which is defined by inflammation, cell death, and fibrosis. The progression to NASH is driven by multiple pathways involving lipid metabolism and steatosis, bile acid synthesis, and insulin resistance.
Cortisol helps regulate the body’s carbohydrate and lipid metabolism. Increased cortisol activity has been implicated in obesity, hyperglycemia, and NAFLD. Modulation of excess cortisol activity can improve insulin sensitivity, reduce triglycerides, and cause weight loss, suggesting that it may also alleviate the fat deposition in NASH.
Neurology
Hypercortisolism is commonly associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), a fatal disorder characterized by damage to motor neurons and progressive paralysis. Many patients with ALS exhibit adrenal hyperfunction, increased plasma cortisol, abnormal circadian rhythms.
Cortisol is a steroid hormone that is made in the adrenal glands and released into the blood. Chronically elevated cortisol levels promote neurodegeneration and neuroinflammation. By reducing the neurotoxic effects of excess cortisol activity, glucocorticoid receptor antagonism may benefit patients with ALS.
Psychiatry
Posttraumatic stress disorder (PTSD) is the most prevalent psychopathological consequence of exposure to traumatic events. Dysregulation of the biological systems that mediate the response to stress plays an important role in the pathophysiology of PTSD. One such biological system is the hypothalamic-pituitary-adrenal (HPA) axis – a self-regulated feedback system that mediates the body’s response to biological and psychological stress. Proper function of the HPA is essential to mental and physical health. Dysregulation of the HPA axis is a hallmark of PTSD. Cortisol modulation, which recalibrates the HPA axis, may have therapeutic benefit in patients with PTSD.
Addictive Disorders
Cortisol is essential to normal physiologic processes and healthy adaptation to stress. Data suggest that people with drug and alcohol addiction have disordered cortisol levels and rhythms that may perpetuate and exacerbate addictive behavior.
Mifepristone Treatment Clinical Trial
INIA Stress and Chronic Alcohol Interactions Clinical Trial
Mifepristone for the Prevention of Relapses Clinical Trial