Method of Treating Immune Pathologies with Low Dose Estrogen
OHSU # 0496
- Halina Offner, SM.Neurology
Combination therapy with low doses of estrogen and an immunotherapeutic agent offers a more effective alternative treatments to ameliorate central nervous system (CNS) symptoms in autoimmune disease, specifically, multiple sclerosis (MS).
Multiple sclerosis is a debilitating neurological autoimmune disease with a higher incidence in women. Relapse rates are known to decrease in women during late pregnancy, when estrogen levels are high. High levels of estrogen are associated with protection from multiple sclerosis in humans and in the animal model, experimental autoimmune encephalomyelitis (EAE), by inhibiting production of inflammatory cytokines and stimulating anti-inflammatory cytokines.
While high dose estrogen therapy offers protection against autoimmune disease it has undesirable side effects. This invention provides a method of ameliorating the neurological effects of MS with low dose estrogen therapy by combining it with an existing immunotherapeutic agent such as glatiramer acetate, interferon β, and T-cell receptor (TCR) peptides. Together, TCR protein and low dose estrogen has shown to induce almost complete protection against EAE. The synergistic effects of combination therapy in inhibiting pathogenic immune responses have great potential for MS treatment and other autoimmune diseases.
• More than 400,000 Americans affected with MS
• More than 2.5 million people around the world have the disease
• MS patients develop clinical signs at about age 30, and require increasing care as their disease progresses and their productivity decreases over the duration of their normal lifespan
• There is no cure for MS. Current treatments include symptom modifying agents that attempt to reduce disease activity and progression, symptom treatment, and methods to improve life functions
•The MS therapeutics market is one of the largest for CNS disorders, with revenues of over $8 billion in 2009 and expected to exceed $12.5 billion by 2015.
There are currently 7 FDA-approved injectable MS therapeutics on the market: interferon β-1b (Avonex, Betaseron, Extavia, Rebif), glatiramer acetate (Copaxone), mitoxantrone (Novantrone), and natalizumab (Tysabri). On September 22, 2010 Gilenya (fingolimod), a drug developed by Norvatis was approved, becoming the first oral MS therapy in the United States. Merck Serono’s oral cladribine is in Phase III and is anticipated to launch at the start of 2011. A few other compound candidates in the MS drug pipeline are daclizumab, dimethyl fumarate, laquinimod, and duloxetine hydrochloride. Our invention provides an extension to MS therapeutics by means of combination therapy with low dose estrogen. Combination therapy is more effective and allows a lower dose of drug to be used than required alone, which reduces potential side effects.
Dr. Halina Offner is a Professor in the Department of Neurology at Oregon Health & Science University with a joint appointment in the Department of Anesthesiology and Peri-Operative Medicine. Her research interests include multiple sclerosis, experimental autoimmune encephalomyelitis, influence of sex hormones on autoimmunity, neuroimmunology, and stroke. Dr. Offner’s work is extensively published, with over 250 articles and book chapters in press.
Bebo BF Jr, Fyfe-Johnson A, Adlard K, Beam AG, Vandenbark AA, Offner H. Low-dose estrogen therapy ameliorates experimental autoimmune encephalomyelitis in two different inbred mouse strains. J Immunol. 2001;166:2080-9
Offer H, Adlard K, Zamora A, Vandenbard AA. Estrogen potentiates treatment with T-cell receptor protein of female mice with experimental encephalomyelitis. J Clin Invest. 2000;105:1465-72
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|Published||Patent Cooperation Treaty||WO01085154|
|Issued||European Patent Convention||0580383.1|
|Issued||Germany||601 29 550.1-08|
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