Technology
Introduction
We all face daily stresses, and the way they affect us depends on many parameters such as the type of stress, its intensity, its duration and whether we see a possible solution. Stress is beneficial when experienced sporadically to handle manageable emergencies.
Stress is bad when experienced chronically in ways that challenges homeostasis irreversibly. At that time every organ can be affected: our skin, gastrointestinal tract, lungs, cardiovasculature, immune, reproductive and central nervous systems.
Two receptors and three native peptides constitute the CRF machinery known to be “A” if not “THE” key controllers of the effects of stress.
Sentia Medical Sciences Inc. has exclusive rights to CRF antagonists (the astressin family members) known to curb excessive stress responses. Whereas unmanageable stress will contribute to diseases or lead to relapses, CRF antagonists will lead to remissions and contribute to recovery.
CRF
Corticotropin Releasing Factor (CRF) is a peptide that stimulates the release of adrenal corticotropic hormone (ACTH), which in turn stimulates the release of corticosteroids from the adrenal cortex. These CRF ligands exert their biological actions on target cells through activation of two CRF receptors, broadly distributed throughout the central nervous system and in several peripheral tissues. CRF plays a major role in the maintenance or restoration of homeostasis by stimulating the activity of the hypothalamicpituitary- adrenal (HPA) axis. It also acts within the brain or locally to modulate the immune, reproductive, gastrointestinal, skin and cardiovascular functions, as well as catecholamine release, drug withdrawal, behavior, mood, and anxiety. CRF signaling is thus a key component of the multifaceted acute response to stress and overactivity of this pathway and has a role in the pathophysiology of various neuroendocrine and psychiatric illnesses related to stress.
The Rivier laboratory has extended the use of his unique "MultiAmide Constrained OligoPeptide" platform (MACOP) to the development of potent and effective receptor antagonist at the CRF receptors: astressin C (a non-selective long acting antagonist) and astressin2-B (a CRFR2-selective antagonist). Astressin C blocks all of the biological actions of CRF and, in preclinical studies, prevents both stress and anxiety-related behaviors induced by CRF. Astressin2-B selectively blocks CRFR2-mediated mostly immune an cardiovascular stress responses. For patients suffering from stress-related disorders, Sentia offers the only potential therapeutic agents that effectively treat their disorder by targeting the root cause of the condition. Irritable bowel syndrome (IBS) is a stress-induced disorder characterized most commonly by cramping, abdominal pain, bloating, constipation, or diarrhea. IBS causes debilitating and disabling discomfort and distress. IBS sufferers may be unable to work, attend social events, or even travel short distances. IBS affects up to 20% of the US population, predominantly women, with associated costs to society running in the billions of dollars.
Hypothesis
CRF peptide antagonists will neutralize the acute or chronic physical or emotional injuries and age-related stresses and reset an unbalanced system to its original homeostatic state (i.e., trigger remissions). This novel concept is based on the observation of the dramatic effects of CRF antagonists on hair regrowth and opens the door to multiple clinical applications that involve the skin, gastrointestinal, immune, cardiovascular, reproductive, or other systems.
Observation
Aging CRF-overexpressing mice that have lost hair on their back, will recover a full coat of hair within two weeks of cessation of treatment consisting of five daily injections of a peptide CRF antagonist.
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sc administration of Astressin B (5ug/mouse) for 5 consecutive days |
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Astressin B injected intraperitoneally (ip) for 5 consecutive days, in adult (alopecic) CRF-Over-expressing mice induces pigmentation and hair re-growth. A, time 0; B, 3 days after last injection and C, 4 weeks after last injection. |
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Astressin B injected subcutaneously (sc) for 5 consecutive days, induces pigmentation and prevents hair loss in young CRF-Over-expressing mice (ABCD) as compared to saline sc-administered controls (EFGH) at times 1, 4, 8 and 16 weeks post last administration. |
Intellectual Property
Exclusive Rights: U.S. application No. 11/766,012, filed June 20, 2007 and PCT No . PCT/US20 07/071695 "Methods for Promoting Hair Growth". CRF antagonists, Patent #s 6,323,312, 5,874,227, 5,777,073 and 7,141,546.
US. Provisional Patent Application No. 61/426,428 "Improved cyclic CRF antagonists"
