46 results about "Sickle cells" patented technology

The invention relates to novel hemoglobin compositions, particularly novel recombinant mutant hemoglobin compositions, which eliminate or substantially reduce 1) the creation of heart lesions, 2) gastrointestinal discomfort, 3) pressor effects, and 4) endotoxin hypersensitivity associated with the administration of extracellular hemoglobin compositions in various therapeutic applications. Applications described include treatments for anemia, head injury, hemorrhage or hypovolemia, ischemia, cachexia, sickle cell crisis and stroke; enhancing cancer treatments; stimulating hematopoiesis; improving repair of physically damaged tissues; alleviating cardiogenic shock; and shock resuscitation.

The present invention provides a therapeutic method for treating an inflammatory response caused by a sickle cell crisis, comprising administration of an effective amount amount of an A2A adenosine receptor agonist. Optionally, the method includes administration of a type IV PDE inhibitor (e.g., rolipram).

A method of preventing pain in a sickle cell patient is disclosed. The method includes orally administering to the patient, an amount of an active agent effective on oral administration to inhibit binding of the patient's sickle erythrocytes to P-selectin on the patient's vascular endothelium. The inhibition may be evidenced in a number of ways. The active agent administration inhibits the adhesion of sickle erythrocytes to vascular endothelium in the patient, thereby preventing patient pain associated with vascular occlusion. Also disclosed are compositions useful in practicing the method.

This invention provides methods utilizing a microfluidic device that can quickly and accurately discern differences in deformability between individual cells and sets of cells and continuously fractionate populations of cells based on their deformability. This information may be important in disease diagnosis and treatment efficacy monitoring. For example such a device may be able to determine the stage of malarial infection by using red blood cell deformability. Additionally, methods of the invention may be used as a tool to screen drugs that can make cells more flexible in diseases such as sickle cell anemia that causes sickle cell crises. The relatively low manufacturing and operation costs of methods of the invention enable this device to be used in resource-limited settings to diagnose and monitor disease.

The present invention relates to methods of treating sickle cell disease comprising reducing, in a subject in need of such treatment, the adherence between sickle RBCs and leukocytes. It is based, at least in part, on the discovery that leukocytes play a direct role in the initiation of venular occlusion. The present invention further provides for methods for identifying agents which decrease SS-RBC / leukocyte adherence and for animal models which may be used to further elucidate the mechanism of vaso-occlusion in sickle cell crises.

Provided are methods for the detection and diagnosis of sickle cell. The methods are based on the discovery that abnormal levels of selected analytes in sample fluid, typically blood samples, of patients who are at risk are supportive of a diagnosis of sickle cell. At least two new biomarkers for sickle cell are thus disclosed, Eotaxin and Monocyte Chemotactic Protein-1. Altogether the concentrations of eleven analytes provide a sensitive and selective picture of the patient's condition, namely, whether the patient is suffering from sickle cell. Other important biomarkers for sickle cell are described, including but not limited to IL-12p40, SHBG, MMP-9, Adiponectin, Haptoglobin, FGF basic, IgM, Growth Hormone, Factor VII. Kits containing reagents to assist in the analysis of fluid samples are also described.

A specific dosage regimen of buprenorphine achieves pain relief from painful episodes due to sickle cell disease. The dosage regimen comprises administering to a patient in need of pain relief from sickle cell disease at least one BTDS transdermal patch. Alternatively, the dosing regimen comprises administering to the patient (1) a first buprenorphine-containing transdermal dosage form for a first dosing period; (2) administering to the patient a second buprenorphine-containing transdermal dosage form for a second dosing period, where the second dosage form comprises the same dosage of buprenorphine as, or a greater dosage of buprenorphine than, the first dosage form; and (3) administering to the patient a third buprenorphine-containing transdermal dosage form for a third dosing period, where the third dosage form comprises a greater dosage of buprenorphine than the second dosage form.

According to the present invention, there is provided a delivery vehicle including sickle red blood cells carrying a moiety. The moiety can be any type of diagnostic or therapeutic agent. The present invention further provides for a method of diagnosing systemic hypoxia, acidosis, or hypertonicity by administering sickle red blood cells to a patient and detecting the location of the sickle red blood cells. Additionally, the present invention provides for a method of therapeutic treatment of systemic hypoxia, acidosis, or hypertonicity by administering sickle red blood cells to a patient. Further, the present invention provides for a delivery vehicle that specifically localizes or concentrates at systemic hypoxia, acidosis, or hypertonicity areas. The delivery vehicle is used in diagnosing and therapeutically treating these areas of hypoxia, acidosis, or hypertonicity also. The present invention further provides for a method of making the delivery vehicle described herein.

Sickle cell patients atypically experience exaggerated inflammatory responses to pathogens that normally cause mild respiratory infections in non-sickle cell humans. There appears to be heightened inflammatory responses to pathogens in combination with hypoxia in sickle cell disease. The novelty of this invention provides a new paradigm to explain the exaggerated inflammatory response of sickle cell disease to pathogens especially when accompanied by hypoxic stress. In particular, sickle cell chest injury and other complications associated with ischemia-reperfusion injury caused by vaso-occlusion can involve co-stimulation of the NALP-3 inflammasome by pathogen associated molecular patterns (PAMPs) and hypoxic-induced danger associated molecular patterns (DAMPs), leading to exaggerated pro-inflammatory responses marked by increased IL-1β secretion and subsequent induction of neutrophilic inflammation. This invention thereby provides the immunologic, biologic and biochemical rationale for IL-1β targeted therapies in sickle cell disease to block the pathological effects of IL-1β that leads to exaggerated inflammatory expressions, including neutrophilic inflammation.

A composition that includes a nanoparticle. The nanoparticle includes a shell which encapsulates sulfated non-anticoagulant heparin (SNACH). The shell includes poly L-arginine. The SNACH is ionically or covalently bonded to the poly L-arginine. A method for treating a disorder of a subject includes: administering to the subject a therapeutically effective amount of the composition for treating the disorder. The disorder is a vascular disorder, a complication of the vascular disorder, or a combination thereof.

The present disclosure is in the field of genome engineering, particularly targeted modification of the genome of a hematopoietic stem cell. Disclosed herein are methods and compositions for altering the expression or for correcting one or more genes encoding proteins involved in a genetic disease (e.g., producing proteins lacking, deficient or aberrant in the disease and / or proteins that regulate these proteins) such as sickle cell disease. The present invention describes compositions and methods for use in gene therapy and genome engineering.

The invention provides compositions and methods for delivering carbon monoxide (CO) to subjects suffering from inflammatory, cardiovascular, Sickle Cell, and other disease. The compositions are liquids, including Newtonian and non-Newtonian liquids, such as pastes, gels, foams, emulsions, and other non-gaseous compositions, in which CO is dissolved at an amount that, when administered to a patient, provides a therapeutically or prophylactically effective amount of CO to the patient. The compositions can be provided in many forms, including in bottles or cans.

The present invention provides compounds useful as medicaments for the treatment of sickle cell disease and diseases characterized by undesirable or abnormal cell proliferation. These compounds are substituted triarylmethane compounds or analogs thereof, wherein one or more aryl groups are partially substituted by heteroaryl, cycloalkyl or heterocycloalkyl groups and / or wherein the quaternary carbon is replaced by a different atom such as silicon, germanium , nitrogen or phosphorus substitution. They inhibit mammalian cell proliferation, inhibit the Gardos channel in cytoplasm, reduce sickle cell dehydration and / or delay red blood cell sickling and deformation.

This patent is an evolution of U.S. Pat. No. 4,216,770 named “sickle cell therapeutic treatment”. That patent is one in which blood is taken out of the subject and treated with anti-sickling agents which are then washed out. In this application blood is removed from a subject and instead filtered to remove diseased cells. The option to introduce anti-sickling agents is then left as a possible option. The filtered cells are then returned to the subject. This technology is superior to other treatments since it can help end sickle cell crises before permanent damage it done. Instead of sickled cells breaking down within the body where they compound damage, they are removed before they can cause problems. More deformable and useful blood cells are retained in the circulation.

Some embodiments of the methods and compositions provided herein relate to modifying hemoglobin loci, such as hemoglobin-related mutations including sickle cell mutations. Some embodiments relate to modification of a sickle cell mutation through introduction of a phosphodiester DNA strand break at the site of the sickle cell mutation.

Resistance of randomly dispersed and oxygen-starved lung tumor cells to chemo- and radiotherapy constitutes the vast majority recurrences and death from lung cancer. We use sickle cells derived from humans with sickle cell anemia to target oxygen-deprived tumor cells that persist and multiply after conventional treatment. Transfused sickle cells selectively occluded tumor microvessels and shut down blood flow to these oxygen-deprived pockets leading to tumor cell death and complete shrinkage of aggressive lung tumors. Combining the sickle cells with a vascular disrupting agents and radiation injure and narrow tumor blood vessels, amplified the scale of sickle cell-induced blood vessel closure and tumor cell killing. The strength of the tumor killing produced by this combination exceeded that of either agent alone or combined with conventional anti-angiogenics, chemotherapy or radiation. Combinatorial sickle cells-Combretastatin treatment thereby constitutes a major advance toward eradicating treatment-resistant tumor cells and reducing the frequency of lung cancer recurrence.

A phytochemical composition for treatment of sickle cell anemia has been developed. The composition is a solid mixture of inorganic salts and various organic compounds of herbal origin and obtained by extracting a mixture of five herbs namely Piper guineenses seeds, Pterocarpus osum stem, Eugenia carophyllum fruit, Sorghum bicolor leaves and Curcuma longa tuber with aquous solution of sodium / potassium bicarbonate and sodium / potassium carbonate and then concentrating the extract to obtain a powder. Also described are methods of preparation of extraction product and method of its use for treatment of sickle cell disease afflicted patients.

The #β-hemoglobinopathies #β-thalassemia (BT) and sickle cell disease (SCD) are the most frequent genetic disorders worldwide. These diseases are caused by mutations causing reduced or abnormal synthesis of the β-globin chain of the adult hemoglobin (Hb) tetramer. Here, the inventors intend to improve HSC-based gene therapy for β-thalassemia and SCD by developing an innovative, highly infectious LV vector expressing a potent anti-sickling β-globin transgene and a second biological function either increasing fetal γ-globin expression (for β-thalassemia and SCD). More particularly, the inventors have designed a novel lentivirus (LV), which carry two different functions: βAS3 gene addition and gene silencing. This last strategy allows the re-expression of the fetal γ-globin genes (HBG1 and HBG2) and production of the endogenous fetal hemoglobin (HbF). Elevated levels of HbF and HbAS3 (Hb tetramer containing βAS3-globin) will benefit the β-hemoglobinopathy phenotype by increasing the total amount of β-like globin that will: (i) reduce the alpha precipitates and improve the alpha / non alpha ratio in β-thalassemia, and (ii) reduce the sickling in SCD. This combined strategy will improve the β-hemoglobinopathy phenotype at a lower vector copy number (VCN) per cell compared to a LV expressing the βAS3 alone.

Improving the antioxidant capacity in an animal by increasing the level of glutathione in the blood or tissue of the animal comprising providing a composition containing beta-casein to the animal for consumption, where the beta-casein comprises at least 75% by weight of one or more beta-caseins not capable of producing beta-casomorphin-7 on enzymatic digestion. Uses include as an oxidant, for treating or preventing the symptoms of cancer, inflammation, kwashiorkor (protein deficiency), seizure, autism, Down's syndrome, chronic fatigue syndrome, Alzheimer's disease, Parkinson's disease, sickle cell anaemia, liver disease, cystic fibrosis, HIV, AIDS, infection, heart attack, stroke, and diabetes, avoiding or reducing the effects of aging, promoting the recovery of tissue following physical exercise, and promoting fertility.

The invention provides compositions and methods for delivering carbon monoxide (CO) to subjects suffering from inflammatory, cardiovascular, Sickle Cell, and other disease. The compositions are liquids, including Newtonian and non-Newtonian liquids, such as pastes, gels, foams, emulsions, and other non-gaseous compositions, in which CO is dissolved at an amount that, when administered to a patient, provides a therapeutically or prophylactically effective amount of CO to the patient. The compositions can be provided in many forms, including in bottles or cans.

A transdermal patch for the treatment of Sickle Cell Ulcers is provided. The patch can facilitate the delivery of an iron chelator, such as DFO. The DFO can be encapsulated in a reverse micelle to enhance penetration into and absorption by the dermis. The patch can be used to accelerate healing and reduce pain associated with Sickle Cell Ulcers.

The present invention provides a compound of Formula (I) and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are PRMT5 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat cancer, sickle cell, and hereditary persistence of foetal hemoglobin (HPFH) mutations.