Evaluative Means For Detecting Inflammatory Reactivity
Description of Invention:
Dysregulations of neuroendocrine stress responses have profound effects on the immune system that are associated with various autoimmune/inflammatory disorders such as rheumatoid arthritis (RA) and psychiatric conditions such as depression and post traumatic stress disorder (PTSD). Inventors from NIMH had previously found that the hypothalamic pituitary adrenal (HPA) hormonal axis, which acts as a regulatory checkpoint between the neuroendocrine and the immune system, is dysregulated in such disorders. Further research now shows that in particular, dysregulation in the secretion of corticotropin releasing hormone (CRH) from the hypothalamus contributes to these conditions. Therefore, the HPA axis, CRH and CRH receptors can serve as major targets for drug development and diagnosis of these diseases.
This patent covers the development of therapeutics and diagnostics for autoimmune/inflammatory diseases that affect millions of people. The patent proposes the use of a wide variety of classes of HPA axis active agents to treat inflammatory illnesses. The patent claims specifically predict that an HPA agonist can be used to treat arthritis. The usefulness and applicability of the patent also extends to the CRH receptor antagonists (e.g., CRH R1 antagonist, Antalarmin) that are now being developed for the treatment of depression and PTSD. Diagnostically, this invention can be used to identify individual susceptibility to autoimmune/inflammatory diseases. Testing of the HPA axis to predict and select responders and non-responders to HPA agonists and CRH receptor antagonists could provide an approach for safe application of such therapeutic agents to a larger proportion of the target population. For example a subject found to have a low HPA axis responsiveness based upon the methods as described in the patent, would be predicted to have a greater risk of developing adrenal insufficiency while being treated with this new class of drugs. Such individuals could then be treated accordingly to prevent adverse events while on CRH antagonist therapy.
Currently, such predictive approaches are not used routinely in clinical settings. The potential of this invention to diagnose and treat certain diseases in a predictive fashion makes it an excellent candidate for simultaneously developing therapeutics and the associated diagnostics. Antalarmin – which is being developed through an NIH initiative - has passed preliminary assessment at the FDA and will soon be in phase I human trials. The inventors found Antalarmin to be effective in reducing clinical arthritis score in rats by 50%, possibly through its blockade of CRH’s peripheral pro-inflammatory effects.
Given that an estimated 43 million people in the United States alone have arthritis or other rheumatic conditions, and that this number is expected to reach 60 million by 2020, this patent holds great potential in further development of therapeutics and diagnostics for autoimmune/inflammatory diseases.
Inventors:
Esther M. Sternberg et al. (NIMH)
Patent Status:
DHHS Reference No. E-289-1988/2 --
U.S. Patent 5,209,920 issued 11 May 1993
Relevant Publication:
F. Eskandari et al., "Neural immune pathways and their connection to inflammatory diseases," Arthritis Res. Ther. 2003, 5(6):251-265.
E.L. Webster et al., "Corticotropin releasing hormone (CRH) antagonist attenuates adjuvant induced arthritis: Role of CRH in peripheral inflammation," J. Rheumatol. 2002 Jun 29(6):1252-1261.
J.I. Webster et al., "Neuroendocrine regulation of immunity," Annu. Rev. Immunol. 2002 20:125-163.
For Additional Information Please Contact: Tara L. Kirby Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4426
Email: tarak@mail.nih.gov
Fax: (301)402-0220
