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United States Patent (10) Patent N0.: US 7,288,257 B2 Powell (45) Date of Patent: Oct

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United States Patent (10) Patent N0.: US 7,288,257 B2 Powell (45) Date of Patent: Oct US007288257B2 (12) United States Patent (10) Patent N0.: US 7,288,257 B2 Powell (45) Date of Patent: Oct. 30, 2007 (54) DIAGNOSIS AND TREATMENT OF HUMAN 5,342,788 A 8/1994 Kunst et a1. .............. .. 436/500 DORMANCY SYNDROME 5,691,456 A 11/1997 AdamcZyk et al. ....... .. 530/405 6,087,090 A 7/2000 Mascarenhas ................ .. 435/4 (76) Inventor: Michael Powell, 150 Catherine Lance, 2003/0007941 A1 1/2003 Cornelius et a1, Suite 1, Grass Valley, CA (US) 95945 ( * ) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 OTHER PUBLICATIONS U.S.C. 154(b) by 199 days. _ Hannah V. Carey, The American Physiological Society, Physical _ Rev 83; Mammalian Hibernation: Cellular and Molecular (21) Appl' NO" 10/444’845 Responses to Depressed Metabolism and Low Temperature, 2003, (22) Filed: May 23, 2003 PP' 1153'1181' _ _ _ Primary ExamineriRuth A Davis (65) Pnor Pubhcatlon Data (74) Attorney, Agent, or F irmiBorson LaW Group, PC; D. US 2003/0228628 A1 Dec. 11, 2003 Benjamin Borson Related US. Application Data (57) ABSTRACT (60) Provisional application No. 60/382,913, ?led on May $112002’ provlslonal apphcanon NO‘ 60/383’271’ New methods for diagnosis of human dormancy syndrome e on May 24’ 2002' are provided. Human dormancy syndrome is characterized (51) Int C1 by elevated serum ratio of rT3/iT 3 compared to a population 1462K 3'9/00 (2006 01) of normal subjects from Which subjects suffering from A 61K 38/22 (200601) ?bromyalgia, chronic fatigue, obesity, dementias including A 61K 38/27 (200601) AlZheimer’s Disease and related dormancy conditions are C1 2 Q 1/00 (200601) excluded, and the presence of one or more ?ndings related ' A / A / A to reduced activity including torpor, chronic fatigue, insulin (52) US. Cl. ..................... .. 424/1981, 435 4, 55330033839, resistance, dementias, Obesity and the like' Treatment of _ _ _ human dormancy syndrome is directed toWard increasing (58) Field of Classi?cation Search ........... .. 424/ 198.1; H3 levels or decreasing {[3 levels’ or both’ using pharma_ _ _ 435/4; 539/380’ 399 ceutical and/or behavioral methods. Other conditions that See apphcanon ?le for Complete Search hlstory' are associated With HDS can also be treated using T3 (56) References Cited therapy, With or Without ~speci?c psychological, behavioral or pharmaceutical therapies. U.S. PATENT DOCUMENTS 5,158,978 A 10/1992 Rubin ...................... .. 514/567 6 Claims, 3 Drawing Sheets U.S. Patent Oct. 30, 2007 Sheet 1 0f 3 US 7,288,257 B2 Relationships between FM, PTSD and HDS Clinical Finding m PTSD HDS Slow wave sleep impaired yes yes yes Irritable Bowel Synhdrome (IBS) yes yes yes, low VIP HPA dysregulation yes yes yes High CRH yes yes yes sympathetic hyperactivity yes yes yes CSF substance P increased increased yes pain perception increased increased serotonin low low yes prolactin increased increased increased growth hormone response blunted blunted yes oxytocin levels low low yes nitric oxide metab abnormal yes yes yes cerebral blood flow centralized centralized yes cognitive function impaired impaired yes orthostatic hypotension yes yes fatigue yes yes yes exercise intolerance yes yes yes mitochondrial impairment yes yes yes hypervigilance yes yes yes compulsivity yes yes detachment/dissociation yes yes depression/anxiety increased increased signi?cant emotional trauma yes yes N/ A impaired NK cell activity yes yes yes FIGURE 1 U.S. Patent Oct. 30, 2007 Sheet 2 0f 3 US 7,288,257 B2 Correlations of FM and Hypothyroidism m Hyp othygoidism Slow Wave sleep impaired yes (8,1 1) yes (157,158) IBS yes (15,16) yes (159,160) HPA dysregulation yes (1922) yes (161-163) High CRH yes (27,28) yes ([62-164) sympathetic hyperactivity yes (32-34) yes (165,166) CSF substance P increased (3941) increased (167-169) pain perception increased (45-47) ? serotonin low (51»53) low (170,171) growth hormone response blunted (61-63) blunted (172,173) oxytocin levels low (65,66) low (174,175) nitric oxide metab abnormal yes (39,52,71) yes (176,177) cerebral blood ?ow centralized (73-75) reduced (178,179) cognitive function impaired (80-82) impaired (180,181) orthostatic hypotension yes (87-89) yes (182) fatigue yes (90-92) yes (1 83) exercise intolerance yes (96-98) yes (184) mitochondrial impairment yes (97,102,103) yes (185,186) hypervigilance yes (104-106) (7) compulsivity yes (15,110) yes (187,188) detachment/dissociation yes (82,113) coma possible depression/ anxiety increased (116-118) increased (189) signi?cant emotional trauma yes (121-125) N/A impaired NK cell activity yes (128-130) yes (190,191) FIGURE 2 U.S. Patent Oct. 30, 2007 Sheet 3 of 3 US 7,288,257 B2 Effects of Dormancy on Physiological Systems Physiological Variable Dormancy Fibromyalgia rT3 high high T3 low low Serotonin low low Melatonin low low Oxytocin low low Prolactin high high Substance P high high HPA axis activity high high Muscle weakness yes yes Exercise intolerance yes yes Memory impairment yes yes low oxygen consumption yes yes Femalezmale Predominance yes yes FIGURE 3 US 7,288,257 B2 1 2 DIAGNOSIS AND TREATMENT OF HUMAN produced in the liver and kidney and released into the blood DORMANCY SYNDROME stream, although most cells have the capacity to convert T4 to T3 or rT3. RELATED APPLICATIONS T3 is metabolically active and stimulates production of cellular energy, and generally is an activator of tissues and This application claims priority under 35 U.S.C. §119 to organs. T3 acts by di?‘using into cells, Where it interacts With US. Provisional Patent Application Ser. No: 60/382,913, a cellular protein Which transports the T3 to the cellular ?led May 23, 2002, and US. Provisional Patent Application nucleus. T3 then acts by stimulating gene transcription to Ser. No: 60/383,271 ?led May 24, 2002, each application produce messenger ribonucleic acids (mRNA) of certain herein incorporated fully by reference. genes. Translation of the T3-induced mRNA produces cel lular proteins that promote cellular activation. In contrast, FIELD OF THE INVENTION rT3 has opposing effects, at least partially by inhibiting the action of T3, by Way of competitively inhibiting T3 nuclear This invention relates to methods for diagnosing and receptors in cells. treating human dormancy syndrome, a constellation of con Thus, the balance betWeen the effects of T3 and rT3 can ditions heretofore unrelated to each other, including ?bro determine the state of cellular activation. In Euthyroid Sick myalgia, autoimmune diseases, coronary artery disease, Syndrome (ESS), conversion of T4 to T3 is inhibited and breast cancer, prostate cancer and AlZheimer’s disease. conversion of T4 to rT3 is elevated. According to the American Thyroid Association, this condition does not War BACKGROUND 20 rant treatment. The American Psychiatric Association rec ogniZes the use of T3 for treatment of depression, and levels of T3 are often decreased in patients With depression, as Well Fibromyalgia is knoWn as a diffuse periarticular muscu as patients With ?bromyalgia. Patients With ?bromyalgia can loskeletal pain syndrome, primarily affecting femalse (90%) have elevated levels of rT3. Dormant animals have elevated and is associated With insomnia, cognitive impairment, 25 rT3 levels. fatigue and depression. Fibromyalgia is also knoWn to be The so-called “Wilson’s Syndrome” is reported to be associated With elevated levels of substance P (SP) in the diagnosed in patients having rT3 and T3 levels, reduced cerebrospinal ?uid (CSF), decreased levels of serotonin body temperature, and clinical ?ndings of arthritis, muscular (5-HT) and a hyperactive hypothalamic-pituitary-adrenal and joint aches, elevated cholesterol and several other ?nd (HPA) axis. The pathophysiological mechanisms underlying 30 1ngs. ?bromyalgia are unknoWn, and the condition is considered Dementias are important causes of morbidity in people uncurable. Exercise, cognitive behavioral therapy and anti suffering from one or more of a variety of underlying depressant medication have been shoWn to diminish the disorders. Typically, dementias present as decreased mental severity of symptoms in some patients, but most patients clarity, decreased memory and complaints of loW energy remain in an unremitting state of illness. Standard laboratory 35 levels, resulting in reduced physical activity. In some tests are normal for most patients having ?bromyalgia, and patients, dementias also present With depression. there is no evidence for autoimmune disease. Interestingly, Treatment of dementias has been limited by the lack of there is an association of ?bromyalgia With a signi?cantly understanding of underlying physiological and pathophysi higher incidence of childhood and adult physical and emo ological mechanisms leading to decreased mental function tional abuse and/or trauma. HoWever, these ?ndings have 40 ing. Treatment of dementias typically are relatively ineffec not been reconciled until the discovery of this invention. tive, and many patients suffering from dementia, especially The hormone triiodithyronine (T3) is a product of the the elderly, do not improve. This is especially true of patients thyroid gland. T3 is synthesiZed in the thyroid gland and is suffering from AlZheimer’s disease, Which is progressive released as thyroxine (T4). T4 is released from the thyroid and ultimately can be fatal. Because of the paucity of gland in response to, among other things, a pituitary hor 45 effective therapies, intense efforts are taking place to under mone, thyroid hormone releasing factor. stand the underlying causes of dementias, including that The hormone L-3,3',5,5',-tetraiodothyronine (L-thyronine associated With AlZheimer’s disease, and to provide effec or T4) is a product of the thyroid gland. T4 is an inactive tive treatments for such conditions. hormone When it is released into the blood stream by the Latasa et al. reported that the [3-amyloid protein, a major thyroid gland.
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