Sickle Cell Patents (Class 514/815)
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Patent number: 6946457Abstract: This invention provides a method of treating a subject afflicted with sickle cell disease which comprises administering to the subject an amount of an antiviral agent effective to inhibit sickling of a cell in the subject, so as to thereby treat the subject afflicted with sickle cell disease. This invention also provides a method of inhibiting polymerization of hemoglobin which comprises contacting the hemoglobin with an amount of an antiviral agent effective to inhibit polymerization of the hemoglobin, so as to thereby inhibit polymerization of the hemoglobin. This invention further provides a method of inhibiting sickling of a cell which comprises contacting the cell with an amount of an antiviral agent effective to inhibit polymerization of hemoglobin in the cell, so as to thereby inhibit sickling of the cell.Type: GrantFiled: April 6, 2001Date of Patent: September 20, 2005Assignee: The Trustees of Columbia University in the City of New YorkInventors: Robert H. DeBellis, Bernard F. Erlanger
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Patent number: 6919374Abstract: It has now been found that N-L-alpha-aspartyl-L-phenylalanine 1-methyl ester (APM) lowers whole blood viscosity in patient, including those suffering from sickle cell disease and plasma cell dyscrasias. Upon in vivo APM treatment patients experienced a significant lowering of whole blood viscosity. In vitro addition of APM to patients samples having elevated whole blood viscosity resulted in reduced viscosity over time. These in vivo and in vivo results identify APM as a therapeutic agent for molecular diseases which lead to elevated whole blood viscosity. A method by which APM treatment can be monitored is also disclosed.Type: GrantFiled: September 21, 2000Date of Patent: July 19, 2005Assignee: Oklahoma Medical Research FoundationInventor: Carl V. Manion
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Patent number: 6635631Abstract: The present invention is directed to complexes comprising iron in the ferric state and a hydroxypyrone. The present invention is also directed to methods of making such complexes and to the use of such complexes in the treatment and prevention of iron deficiency disorders including iron deficiency anaemia.Type: GrantFiled: October 25, 2001Date of Patent: October 21, 2003Assignee: Vitra Pharmaceuticals, Ltd.Inventors: Michael Arthur Stockham, Robert Charles Hider
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Patent number: 6339080Abstract: The present invention is directed to complexes comprising iron in the ferric state and a hydroxypyrone. The present invention is also directed to methods of making such complexes and to the use of the complexes in the treatment and prevention of iron deficiency disorders including iron deficiency anaemia.Type: GrantFiled: December 9, 1997Date of Patent: January 15, 2002Assignee: Vitra Pharmaceuticals Ltd.Inventors: Michael Arthur Stockham, Robert Charles Hider
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Patent number: 6087398Abstract: The present invention provides a method of treating sickle cell anemia comprising the step of administering to an individual in need of said treatment a therapeutically acceptable dose of reducing agent. In yet another embodiment of the present invention, there is provided a method of pharmacologically correcting a post-translational modification of the .beta.-actin protein in sickled erythrocytes, comprising the step of contacting said sickled erythrocytes with a pharmacologically effective dose of a reducing agent. In still yet another embodiment of the present invention, there is provided a method of identifying a drug for use in treating sickle cell anemia. Any drug which hastens the HDSS Core Skeleton dissociation rate is tested by the in vitro ternary complex dissociation assay to test whether its effect is on HDSS beta-actin. Furthermore, drugs can be tested by the oxygenation-deoxygenation cycling assay for its ability to block ISC formation in vitro.Type: GrantFiled: March 1, 1996Date of Patent: July 11, 2000Assignee: South Alabama Medical Science FoundationInventor: Steven R. Goodman
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Patent number: 6083984Abstract: Two new forms of prodrug for phenylacetate, of even congeners of phenylalkanoic acid and phenylalkenoic acids, which are the phenylalkanoic or phenylalkenoic esters of glycerol, or the ethyl esters of phenylalkanoic acid or phenylalkenoic acids. These forms of the drugs provide a convenient dosage form of the drugs. The prodrugs of the invention are useful to treat patients with diseases of nitrogen accumulation, patients with certain .beta.-hemoglobinopathies, anemia, and cancer.Type: GrantFiled: May 25, 1999Date of Patent: July 4, 2000Assignee: Brusilow Enterprises LLCInventor: Saul W. Brusilow
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Patent number: 6060510Abstract: Two new forms of prodrug for phenylacetate, of even congeners of phenylalkanoic acid and phenylalkenoic acids, which are the phenylalkanoic or phenylalkenoic esters of glycerol, or the ethyl esters of phenylalkanoic acid or phenylalkenoic acids. These forms of the drugs provide a convenient dosage form of the drugs. The prodrugs of the invention are useful to treat patients with diseases of nitrogen accumulation, patients with certain .beta.-hemoglobinopathies, anemia, and cancer.Type: GrantFiled: May 25, 1999Date of Patent: May 9, 2000Assignee: Brusilow Enterprises LLCInventor: Saul W. Brusilow
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Patent number: 5968979Abstract: Two new forms of prodrug for phenylacetate, of even congeners of phenylalkanoic acid and phenylalkenoic acids, which are the phenylalkanoic or phenylalkenoic esters of glycerol, or the ethyl esters of phenylalkanoic acid or phenylalkenoic acids. These forms of the drugs provide a convenient dosage form of the drugs. The prodrugs of the invention are useful to treat patients with diseases of nitrogen accumulation, patients with certain .beta.-hemoglobinopathies, anemia, and cancer.Type: GrantFiled: January 13, 1998Date of Patent: October 19, 1999Assignee: Brusilow Enterprises LLCInventor: Saul W. Brusilow
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Patent number: 5919755Abstract: The invention is to a method for stimulating the production of fetal hemoglobin in a mammal having a hemoglobinopathy, comprising administering heme or a derivative thereof.Type: GrantFiled: July 28, 1997Date of Patent: July 6, 1999Assignee: Leiras OYInventors: Mauno Kangasaho, Klaus Relander
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Patent number: 5885621Abstract: Disclosed are methods for treating a patient identified as having a hemoglobinopathy that is characterized by a reduced affinity of hemoglobin for oxygen. The methods involve providing gaseous nitric oxide and/or carbon monoxide for (i) inhalation by the patient or (ii) ex vivo treatment of the patient's erythrocytes. Alternatively, a nitric-oxide-releasing compound can be administered to the patient.Type: GrantFiled: April 4, 1997Date of Patent: March 23, 1999Assignee: The General Hospital CorporationInventors: C. Alvin Head, Warren M. Zapol
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Patent number: 5846528Abstract: The use of recombinant adeno-associated virus (AAV) virions for delivery of DNA molecules to muscle cells and tissue in the treatment of anemia is disclosed. The invention allows for the direct, in vivo injection of recombinant AAV virions into muscle tissue, e.g., by intramuscular injection, as well as for the in vitro transduction of muscle cells which can subsequently be introduced into a subject for treatment. The invention provides for sustained, high-level expression of a delivered nucleotide sequence encoding erythropoietin, and for in vivo secretion thereof from transduced muscle cells such that systemic delivery is achieved.Type: GrantFiled: January 16, 1997Date of Patent: December 8, 1998Assignees: Avigen, Inc., Johns Hopkins UniversityInventors: Gregory M. Podsakoff, Gary J. Kurtzman
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Patent number: 5800819Abstract: A phytochemical composition for treating sickle cell disease is provided. The composition is a cold water extraction product of a mixture containing Piper guineenses seeds, Pterocarpus osum stem, Eugenia caryophyllum fruit, Sorghum bicolor leaves and potash.Type: GrantFiled: January 21, 1997Date of Patent: September 1, 1998Assignee: National Institute for Pharmaceutical Research and Development Federal Ministry of Science and TechnologyInventors: Charles Wambebe, P. O. Ogunyale, K. S. Gamaniel, R. N. Nasipuri, J. I. Okogun, Babatunde Samuel, Akin Olusola, Abayomi Orisadipe
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Patent number: 5750132Abstract: The present invention relates to methods of lessening the severity and frequency of adverse effects associated with administration of extracellular hemoglobin comprising administration of a smooth muscle relaxant. Preferred smooth muscle relaxants are terbutaline and nifedipine, which can be administered in a prophylactic treatment, responsive regimented treatment or responsive intermittent treatment.Type: GrantFiled: May 26, 1995Date of Patent: May 12, 1998Assignee: Somatogen, Inc.Inventor: Michael J. Gerber
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Patent number: 5669396Abstract: Methods are described for treating sickle cell disease, and in particular, detection and treatment of vaso-occlusive crisis in sickle cell disease. Antibodies are employed which bind competitively and suppress adhesion of sickle erythrocytes to autologous lymphocytes.Type: GrantFiled: January 16, 1996Date of Patent: September 23, 1997Assignee: President and Fellows of Harvard CollegeInventors: David Eric Golan, Hemant Sadashiv Thatte, Alexandru Cristian Bageac
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Patent number: 5585399Abstract: The present invention relates to a method of using a preparation of triacylglycerol which contains unsaturated fatty acids having no more than two double bonds to preserve normal erythrocyte deformability, to improve microcirculation, to protect myocardium against ischemic damage and to suppress arrhythmia in ischemic heart, i.e. to protect cells and tissues of a mammalian body against various forms of mechanical and chemical injuries.Type: GrantFiled: January 18, 1994Date of Patent: December 17, 1996Inventors: Chuang-Ye Hong, Li-Ju Lai, Sheau-Farn Yeh
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Patent number: 5569675Abstract: This invention relates to novel methods of increasing the level of fetal hemoglobin (HbF) in a subject and methods of treating, preventing or ameliorating .beta.-globin or other HbF-related disorders by increasing the level of HbF in a subject in need of such treatment comprising administering one or more compounds of the Formulae (I), (II), or (III):(I) XCH.sub.2 --CHX--CHX--C(.dbd.O)--O--Z(II) CH.sub.3 --CO--CH.sub.2 --C(.dbd.O)--O--Z(III) CH.sub.3 --CH.sub.2 --CO--C(.dbd.O)--O--Zwherein:X is H, or one of X only may be OH;Z is --CHR--O--C(.dbd.O)R', --CHR--O--C(.dbd.Type: GrantFiled: March 7, 1994Date of Patent: October 29, 1996Assignees: Bar Ilan University, Mor Research Applications Ltd.Inventors: Ada Rephaeli, Abraham Nudelman, Matityahu Shaklai
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Patent number: 5447720Abstract: A composition and method of treatment of hemoglobinopathies, such as, for example, sickle cell disease and thalassemia, wherein an inventive extract used in such treatment is obtained from alfalfa and other certain plant materials, preferably using a hydroxide base and hexane. In the most preferred embodiment, the plant material is first extracted with 1,1,1-trichloroethane and a hydroxide base, followed by extraction with hexane. The polar acidic compounds present in alfalfa and other plant materials selectively dissolve in the hexane phase and exhibit good antisickling activity in vitro. Further, these active compounds which comprise the inventive extract are effective in vivo by significantly alleviating the many clinical manifestations of sickle cell disease and thalassemia experienced by the affected patients.Type: GrantFiled: July 6, 1993Date of Patent: September 5, 1995Assignee: Sunday O. FaduluInventor: Sunday O. Fadulu
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Patent number: 5439939Abstract: This invention relates to treatment of betaglobin disorders, such as sickle-cell anemia and beta-thalassemia, by administering compositions of isobutyramide.Type: GrantFiled: March 17, 1992Date of Patent: August 8, 1995Assignee: Children's Hospital Medical Center of Northern CaliforniaInventor: Susan P. Perrine
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Patent number: 5273992Abstract: The present invention provides a chemical class of active compounds to be used as efficacious drugs in the treatment of sickle cell disease. The active compounds include imidazole derivatives, nitroimidazole derivatives, and triazole derivatives. These compounds are to be administered by any preferred route of administration including oral, intramuscular, intravenous, and any other parenteral route. If desired, these drugs may also be administered transmucosally, or subcutaneously, or using a dermal patch on the skin. In addition, the methodology is effective for both long term and short term therapy; may be employed prophylactically and/or therapeutically; and may be used in emergency, acute crisis clinical situations.Type: GrantFiled: November 2, 1992Date of Patent: December 28, 1993Assignee: Beth Israel Hospital Assoc. Inc.Inventors: Carlo Brugnara, Seth L. Alper
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Patent number: 5225447Abstract: The major component of the carbonate fraction of free acids extractable from alfalfa has shown excellent control of symptoms in patients with sickle cell disease. Its structure has been established by proton NMR spectrometry as being 16-hydroxy-9Z,12Z,14E-octadecatrienoic acid and closely related compounds, such as simple esters, amides, triglycerides, or other derivatives of the carboxylic acid function, and a method for its synthesis from linseed oil or methyl linolenate has been developed. The product from linseed oil, both in the form of the initially formed triglyceride and in the form of its free acid obtained by saponification, is useful for the treatment of sickle cell disease.Type: GrantFiled: February 14, 1992Date of Patent: July 6, 1993Assignee: Omex International, Inc.Inventor: Alfred J. Weinheimer
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Patent number: 5177208Abstract: A method for preventing the sickling of sickle cells in a patient having sickle cell disease, the method which comprises administering to the patient a therapeutically effective amount of a compound having the formula: ##STR1## wherein X.sup.- is selected from the group consisting of iodide, chloride, bromide, hydroxyl, nitrite, phosphate and acetate.Type: GrantFiled: January 13, 1992Date of Patent: January 5, 1993Inventor: Michael Wilburn
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Patent number: 5108754Abstract: A method for preventing the sickling of sickle cells in a patient having sickle cell disease, the method which comprises administering to the patient a therapeutically effective amount of a compound having the formula: ##STR1## wherein X.sup.- is selected from the group consisting of iodide, chloride, bromide, hydroxyl, nitrite, phosphate and acetate.Type: GrantFiled: February 8, 1991Date of Patent: April 28, 1992Inventor: Michael Wilburn
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Patent number: 5025029Abstract: A method is provided for inhibiting the .gamma. to .beta.-globin switching in subjects afflicted with .beta.-globin disorders. The method is particularly adapted for ameliorating the clinical symptoms of sickle cell anemia by periodically introducing butyrate, or certain isomers, homologs, analogs or chemical variations thereof, into the bloodstream of the subject prior to natural completion of the switching process.Type: GrantFiled: May 4, 1990Date of Patent: June 18, 1991Assignee: Children's Hospital Medical Center of Northern CaliforniaInventor: Susan Perrine
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Patent number: 5006512Abstract: The invention provides novel therapeutic usages of inhibitors of a potassium channel of the cells. Since the increase of the intracellular calcium concentration is known to trigger various reactions which destroy the cells, the prevention of calcium entry by calcium channel blockers are known to be beneficial in protecting cell membranes in ischemic and traumatic injuries. However, the importance of potassium ions in cell injuries has not been well recognized. Using charybdotoxin (which is not a calcium channel blocker, but is a potassium channel blocker), the inventor found that this compound as well as related compounds have protecting effects in brain is chemia, liver ischemia and spinal cord injury at an extremely low concentration (0.05-0.14 mg/kg body weight). In in vitro experiments, these compounds inhibited the irreversible denaturation of sickle red cell membranes caused by sickling-unsickling stress at an extremely low concentration (2.times.10.sup.-8 M).Type: GrantFiled: December 22, 1988Date of Patent: April 9, 1991Inventor: Tsuyoshi Ohnishi
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Patent number: 4904678Abstract: Method of providing anti-sickling of red blood cells in sickle cell anemia patients without hemolyzing said cells, using thiocyanates alone, or together with Vitamin B.sub.6.Type: GrantFiled: August 25, 1987Date of Patent: February 27, 1990Assignee: Jerome J. NorrisInventor: Oji A. Chima
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Patent number: 4851404Abstract: A therapeutic method of treatment of hemoglobinopathy by administration of a drug capable of blocking the Ca.sup.+2 channel in and out of muscle cells. Drugs known to possess this capability are 1,4-dihydropyridines, .beta.-phenethylamines, benzothiazepines, ethylenediamines and diaryl alkyl amines. These drugs are known to block the influx of Ca.sup.+2 into the cardiac muscle and are known to be useful in treatment of such heart muscle conditions as angina. It has now been unexpectedly discovered that such drugs can be used to treat hemoglobinopathy.Type: GrantFiled: January 15, 1985Date of Patent: July 25, 1989Assignee: Miles Inc.Inventor: S. Tsuyoshi Ohnishi
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Patent number: 4835146Abstract: Treatment of sickle cell disease using danazol.Type: GrantFiled: June 8, 1987Date of Patent: May 30, 1989Assignee: University of MiamiInventors: William J. Harrington, Yeon S. Ahn, Ravindra Mylvaganam
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Patent number: 4822821Abstract: A method is provided for inhibiting the .gamma. to .beta.-globin switching in subjects afflicted with .beta.-globin disorders. The method is particularly adapted for ameliorating the clinical symptoms of sickle cell anemia by periodically introducing into the bloodstream of the subject prior to natural completion of the switching process .alpha.-amino-n-butyric acid, butyric acid, isomers or salts thereof, insulin, histone deacetylase inhibitors, or mixtures thereof.Type: GrantFiled: October 10, 1986Date of Patent: April 18, 1989Assignee: Children's Hospital Medical Center of Northern CaliforniaInventor: Susan Perrine
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Patent number: 4751244Abstract: The present invention is directed to compounds of the general formula I and pharmaceutically acceptable salts thereof: ##STR1## wherein: R.sup.1 =HO or HOOC(CH.sub.2).sub.x CHR.sup.2 NH--;R.sup.2 =H, lower alkyl, benzyl or --CH.sub.2 OH;x=0 or 1;A=--(CH.sub.2).sub.n -- or ##STR2## n=1 to 5; and Y=H, Cl or OCH.sub.3Z=H or Clm=0 or 1R=lower alkyl;with the proviso that where R.sup.1 =OH, Y is H or Cl and m is 1, n is 4 or 5.The present invention is also directed to an antisickling pharmaceutical carrier and an antisickling agent of the general formula (I) (without the proviso) and pharmaceutically acceptable salts thereof.Type: GrantFiled: April 30, 1987Date of Patent: June 14, 1988Assignees: Merck & Co., Inc., The University of PittsburghInventors: Donald J. Abraham, Otto W. Woltersdorf, Jr., Edward J. Cragoe, Jr.
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Patent number: 4731381Abstract: The present invention is directed to a method of treating a person for sickle cell anemia comprising administering to the person a therapeutically effective dosage of a compound of the general formula (I) and pharmaceutically acceptable salts thereof: ##STR1## wherein: R=ethyl, propyl or isopropyl; and ##STR2##Type: GrantFiled: April 4, 1986Date of Patent: March 15, 1988Assignee: Merck & Co., Inc.Inventors: Donald J. Abraham, Edward J. Cragoe, Jr., Otto W. Woltersdorf, Jr.
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Patent number: 4704402Abstract: A method of treating a person for sickle cell anemia including administering to the person a therapeutically effective dosage of the compound ##STR1## wherein at least one R=Cl, BR, CH.sub.3 or OCH.sub.3 and each other R=H, R'=H or CH.sub.3 and n=1, 2, 3, 4 or 5. The compound is preferably selected from the group consisting of clofibrate, clofibric acid, p-chlorophenoxyacetic acid and phenoxyacetic acid. It is preferably administered in solid dosage form and may advantageously be employed in prophylactic treatment to resist sickle cell crises.Type: GrantFiled: November 21, 1983Date of Patent: November 3, 1987Assignee: University of PittsburghInventors: Donald J. Abraham, Donald Witiak
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Patent number: 4665058Abstract: The invention provides a new composition and method for the treatment of sickle cell anemia. The composition includes as an active ingredient an effective amount of the compound, phlorizin benzylazide: ##STR1## and an appropriate pharmaceutical excipient. Load and maintenance dosage ranges as well as effective blood concentration levels for the active ingredient are disclosed.Type: GrantFiled: March 16, 1985Date of Patent: May 12, 1987Assignee: The University of Kentucky Research FoundationInventors: Donald F. Diedrich, Christopher L. Maynard
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Patent number: 4613616Abstract: The present invention relates to polymeric iron chelators based upon hydroxamic acids having the general formula: ##STR1## wherein R is hydrogen or lower alkyl. The present compound is useful for the treatment of iron overload disorders particularly arising from iron poisoning and the disease .beta.-thalassemia otherwise known as Cooley's Anemia. The polymeric hydroxamic acids of the present invention exhibit high selectivity for iron, good water solubility for both the chelator and its iron complex, low toxicity and, most significantly, increased bioactivity, i.e., the ability to remove iron in vivo.Type: GrantFiled: July 20, 1984Date of Patent: September 23, 1986Assignee: Research CorporationInventors: Anthony Winston, D. V. P. R. Varaprasad
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Patent number: 4535183Abstract: This invention is directed to novel ether compounds of formula (I) ##STR1## which are of value in medicine in the palliation of haemoglobinopathies, in particular sickle-cell anemia, and also in the palliation of pulmonary dyefunction, protection from the effects of hypoxia and the radio-sensitization of tumours. The invention is also directed to methods for the preparation of the ether compounds, to pharmaceutical formulations containing them, the preparation of such formulations and the use of the compounds in human medicine. Also provided by the invention are intermediates of value in the preparation of the ether compounds, by the methods described, and the preparation of the intermediates.Type: GrantFiled: December 18, 1981Date of Patent: August 13, 1985Assignee: Burroughs Wellcome Co.Inventor: Geoffrey Kneen
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Patent number: RE36080Abstract: A method is provided for inhibiting the .gamma. to .beta.-globin switching in subjects afflicted with .beta.-globin disorders. The method is particularly adapted for ameliorating the clinical symptoms of sickle cell anemia by periodically introducing butyrate, .Iadd..alpha.-amino-n-butyric acid, .Iaddend.or .?.certain isomers, homologs, analogs or chemical variations thereof,.!. .Iadd.isobutyramide .Iaddend.into the bloodstream of the subject prior to natural completion of the switching process.Type: GrantFiled: June 18, 1993Date of Patent: February 2, 1999Assignee: Children's Hospital Medical Center of Northern CaliforniaInventor: Susan P. Perrine