SCIENTIFIC OVERVIEW
Addressing the debilitating effects of glucocorticoid (steroid) excess.
A new understanding of active steroid regulation.
Traditionally, physicians have focused on excess steroid levels circulating in the bloodstream. But what’s more important is the level of active steroids available intracellularly to cause toxicities in key tissues, such as the liver, adipose (fat), bone, and brain. Intracellularly, active steroids are predominantly regulated by HSD-1.
HSD-1 inhibition can reduce the ratio of active cortisol to inactive cortisone in the liver by 90%¹
How we’re modulating steroids.
By utilizing therapies that inhibit HSD-1 we can lower intracellular levels of active steroids in key tissues, thereby potentially reducing many of the adverse effects of steroid excess. Our proprietary HSD-1 inhibitor is being developed for endocrine disorders caused by an overproduction of cortisol: endogenous Cushing’s syndrome and autonomous cortisol secretion.
And maintaining their utility.
As HSD-1 does not appear to be a dominant factor in a range of immune responses, HSD-1 inhibition may not affect the anti-inflammatory efficacy of steroid medicines. This insight provides the basis for our combination therapy SPI-47, which combines our proprietary HSD-1 inhibitor with an effective steroid medicine. It is designed to treat patients with autoimmune diseases like PMR, potentially achieving the efficacy of steroids without many of the current side effects.
Health outcomes caused by excess glucocorticoids:
Diabetes
Impaired Healing
Weight Gain
Depression
Heart Disease
Insomnia
Bone Fractures
Glaucoma
Muscle Weakness
Memory Loss
Luis, Cushing’s patient
“Last year, I was diagnosed with Cushing’s syndrome. Though I had surgery, my tumor has reoccurred and continues to cause severe symptoms. Now, my only options involve all kinds of testing and multiple pills or injections every day. To top it off, every drug leads to side effects that are nearly as bad as the disease itself. I’m desperate for a better solution.”
Carl, ACS patient
“I’m the CEO of an investment firm. I’ve spent the last few years trying to hide my growing back pain, my struggle with diabetes, and worst of all, my constant brain fog. My doctor was never able to tell me why I have all these problems despite my healthy lifestyle. Now I know it’s because of ACS and the only treatment is to risk having surgery.”
Mary, PMR patient
“My arms and legs are growing stiffer by the day. After consulting my doctor, I was given two choices: Live with the increasingly painful symptoms of PMR or take a drug that is likely to worsen my hypertension and make me more susceptible to bone fractures – among other terrible side effects. Can I have a third option?”
¹ Liu, Wei, et al. American College of Clinical Pharmacology, 2013. https://accp1.onlinelibrary.wiley.com/doi/pdf/10.1002/cpdd.5.