131 results about "Sickle Cell Diseases" patented technology

The present disclosure relates to compositions and methods of increasing levels of fetal hemoglobin (HbF) in cells. The present disclosure further relates to methods for treating patients suffering from blood cell diseases, including those associated with reduced amounts of functional adult hemoglobin (HbA), such as sickle cell disease and β-thalassemias

The invention relates to the technical field of stem cells, in particular to a lentivirus envelope plasmid combination and application thereof, a lentivirus and a packaging method thereof and a method for transduction of hematopoietic stem cells. The invention provides an envelope plasmid combination for lentivirus packaging, which is composed of lentivirus packaging plasmids containing VSVG glycoprotein and lentivirus packaging plasmids containing BaEV glycoprotein in a ratio of 3: 7. The invention further provides a method for transduction of the hematopoietic stem cells by the lentivirus, the method is simple and convenient to operate, the long-term dryness of the hematopoietic stem cells in vitro can be maintained, efficient and stable transduction of the hematopoietic stem cells can be realized, and the transduction rate is greater than 90%. The lentivirus transduction method hematopoietic stem cells can be used for hematopoietic stem cell gene therapy hematopoietic system genetic diseases, such as severe combined immunodeficiency, beta-thalassemia and sickle cell disease, Wiskott-Aldrich syndrome and the like, and the application prospect is good.

The invention relates to substituted pyrazolo piperidine carboxylic acids, their salts and to processes for their preparation, and also to their use for preparing medicaments for the treatment and / or prophylaxis of diseases, in particular cardiovascular and cardiac diseases, preferably heart failure with reduced and preserved ejection fraction (HFrEF, HFmrEF and HFpEF), hypertension (HTN), peripheral arterial diseases (PAD, PAOD), cardio-renal and kidney diseases, preferably chronic and diabetic kidney disease (CKD and DKD), cardiopulmonary and lung diseases, preferable pulmonary hypertension (PH), and other diseases, preferably neurodegenerative diseases and different forms of dementias, fibrotic diseases, systemic sclerosis (SSc), sickle cell disease (SCD), wound healing disorders such as diabetic foot ulcer (DFU).

The disclosure provides compositions and methods for the treatment and / or prevention of sickle cell disease.

In certain embodiments, a lentiviral vector for the treatment of sickle cell disease (SCD) is provided. In certain embodiments, the vector comprises an expression cassette that encodes that an anti-sickling β-globin gene and an shRNA that inhibits expression of a BCL11A gene (BCL11A shRNA) wherein said expression cassette is in reverse orientation in the vector; a β-globin locus control region (LCR) comprising a reduced length hypersensitive site 1 (HS1) sequence, a reduced length hypersensitive site 2 (HS2) sequence, a reduced length hypersensitive site 3 (HS3) sequence, and a reduced length hypersensitive site 4 (HS4) sequence, where said anti-sickling β-globin gene is operably linked to the human β-globin locus control region.

Methods for treating Sickle Cell Disease (SCD) comprising administering a BTKi, such as at least one compound chosen from (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile (rilzabrutinib) and pharmaceutically acceptable salts thereof, are disclosed.

The invention relates to haptoglobin or a nucleic acid encoding haptoglobin for use in treating or preventing of exaggerated erectile response and / or preventing permanent erectile dysfunction. In addition, the invention relates a pharmaceutical composition for use in treating or preventing exaggerated erectile response and / or preventing permanent erectile dysfunction, wherein the pharmaceutical composition comprises an adeno-associated viral (AAV) vector with a transgene encoding a haptoglobin gene. The exaggerated erectile response may be priapism, for example priapism associated with sickle cell disease (SCD).

Provided herein are crystalline salt and free base forms and amorphous forms of a compound having the following formula (I): (I) Compound 1. Also provided are pharmaceutical compositions comprising such crystalline and amorphous forms, processes for their manufacture and their use for the treatment of various conditions such as hemolytic anemia, sickle cell disease and MDS (very low risk MDS, low risk MDS, lower risk MDS and / or moderate risk MDS).

A 2-aminoarylthiazole derivative or a pharmaceutically acceptable salt or solvate thereof, in particular masitinib or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of sickle cell disease in a patient in need thereof. Also, a 2-aminoarylthiazole derivative or a pharmaceutically acceptable salt or solvate thereof, in particular masitinib or a pharmaceutically acceptable salt or solvate thereof, for use in the prevention and / or treatment of acute chest syndrome (ACS) in a sickle cell disease patient in need thereof.

Aspects of the present disclosure provide anti-TMPRSS6 antibodies and methods of using the same to promote hepcidin expression and treat iron overload related disorders such as hemopigmentation, sickle cell disease, thalassemia, hemolysis, Diamond-Blackfan anemia, myelodysplastic syndrome (MDS), and blood transfusion.

The present invention relates to inhibitors of protein fucosylation. More specifically, the present invention relates to carbocyclic compounds of formula (I) useful as inhibitors of protein fucosylation, or for the treatment of cancer, autoimmune diseases, infectious diseases, inflammatory diseases, or sickle cell diseases.

The present invention relates to nicotinamide mononucleotide derivatives of Formula (I)for use in the treatment and / or prevention of a blood disorder, especially sickle cell disease. The present invention further relates to pharmaceutical compositions comprising compounds of Formula (I) for use in the treatment and / or prevention of a red blood cell disorder, especially sickle cell disease.

Provided herein is a method of treating a blood disorder such as sickle cell disease or a β-hemoglobinopathy with an Embryonic Ectoderm Development (EED) inhibitor as described herein.

The invention concerns a method for determining, by flow cytometry, the hemoglobin content of each erythroid cell of a set of erythroid cells. This method applies in particular to determining the hemoglobin content of each red blood cell of a set of red blood cells. The invention also concerns a method for determining the amount of red blood cells transfused into a patient and for monitoring the therapeutic efficacy of a treatment for sickle cell disease or β-thalassemia.

The present invention relates to products and compositions and their uses. In particular, the invention relates to nucleic acid products that interfere with the expression of the TMPRSS6 gene or inhibit its expression and to therapeutic uses such as for the treatment of hemochromatosis, porphyria and hematological disorders such as β-thalassemia, sickle cell disease and iron overload from transfusions or myelodysplastic syndrome.

The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which bind to P-selectin. The invention also relates to multimeric binding complexes of polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold that are binders of P-selectin. The invention also includes drug conjugates comprising said peptides and complexes, conjugated to one or more effector and / or functional groups, to pharmaceutical compositions comprising said peptide ligands, complexes and drug conjugates and the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by a cell adhesion molecule, such as P-selectin, including vaso-occlusive crisis and sickle cell disease-related conditions, cancer, or COVID-19.

Methods and compositions for increasing hemoglobin levels (e.g., fetal hemoglobin) and / or gamma-globin in a cell or subject by the administration of at least one FTP A inhibitor and / or at least one TIPRL inhibitor to the cell or subject is disclosed. In another aspect methods of treating and / or preventing a hemoglobinopathy (e.g., sickle cell disease) or thalassemia in a subject by the administration at least one PTPA inhibitor and / or at least one TIPRL inhibitor to the subject in need thereof are further disclosed.

The present invention relates to nicotinamide mononucleotide derivatives of formula (I) for use in the treatment and / or prevention of blood disorders, in particular sickle cell disease. The invention also relates to a pharmaceutical composition comprising the compound of formula (I) for use in the treatment and / or prevention of erythrocyte disorders, in particular sickle cell disease.

The subject disclosure relates to microbiome-based agents, compositions and methods for treatment or prevention of pain, osteoarthritis, and other complications in a subject (e.g., a subject with a sickle cell disease). In particular, the present disclosure relates to compositions comprising probiotic microorganisms and uses of such compositions for treating, preventing or reducing pain and osteoarthritis in a subject.

The present invention relates to a nicotinamide mononucleotide derivative of formula (I) which is used for treating and / or preventing blood disorders, especially sickle cell disease. The present invention also relates to a pharmaceutical composition comprising a compound of formula (I) which is used for treating and / or preventing red blood cell disorders, especially sickle cell disease.

The present disclosure provides compositions and methods for the treatment and / or prevention of sickle cell disease.

Disclosed herein are potency assays for a gene therapy treatment for sickle cell disease. Also disclosed herein are methods for measuring relative potency of a drug product used for the treatment of sickle cell disease.

The present application relates to the use of idasanutlin, or a pharmaceutically acceptable salt, a solvate, an isomer, or a functional derivative thereof for the treatment of hemoglobinopathies, including sickle cell disease, thalassemia, sickle cell beta thalassemia (Hb S / β Th), and leukocytosis as well as myeloproliferative conditions, polycythemia, and acute and chronic hemolytic anemia. It was found that idasanutlin increases HbF levels in multipotent erythroleukemia, hematopoietic stem cells, and sickle cell disease cells to provide another therapy for treatment of sickle cell disease.

Disclosed herein are methods of mobilizing hematopoietic stem and progenitor cells (HSPC) in a subject in need thereof, the methods include administering one or both of (1) an inhibitor of the polymerization of hemoglobin S and (2) a P-selectin or E-selectin inhibitor, prior to administering a hematopoietic stem cell mobilizing agent.

A product, composition, suspension and / or method to dissolve vaso-occlusive clots in vivo in a sickle diseased subject utilizing Target-specific Thrombolytic Urokinase Spheres (TTUS). The TTUS can target vaso-occlusive clots in vivo and then lyse the obstructive blood clots with high efficiency can be intravenously administered to a subject in need thereof. The TTUS are configured to dissolve vaso-occlusive clots by converting plasminogen in blood of the subject into plasmin molecules that dissolves the clot. The nanospheres can encapsulate an enzymatically active bioreactive agent, such as urokinase. Since the active enzyme is targeting and binding essentially only to obstructive clots, there is minimal risk of side-effects to the subject. The nanospheres are less than one micron in diameter, resulting in a size much smaller than red blood cells.

A method of mobilizing CD34 + cells in a subject suffering from sickle cell disease (SCD) is provided. The method comprises the following steps: a therapeutically effective amount of CXCR4 inhibitory peptide shown as SEQ ID NO: 1 and a therapeutically effective amount of natazumab are applied to a subject, and the natazumab and the CXCR4 inhibitory peptide are sequentially applied. Also provided is the use of mobilized cells for subsequent treatment of SCD in gene therapy.

The present invention relates to nicotinamide mononucleotide derivatives of Formula (I)for use in the treatment and / or prevention of a blood disorder, especially sickle cell disease. The present invention further relates to pharmaceutical compositions comprising compounds of Formula (I) for use in the treatment and / or prevention of a red blood cell disorder, especially sickle cell disease.

The present application relates to use of a hypoxia-inducible factor-prolyl hydroxylase inhibitor (HIF-PHI) in rare anemia. Specifically disclosed in the present application is use of certain hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) in the treatment of anemia of myelodysplastic syndromes (MDS anemia), beta-thalassemia (β-thalassemia), and / or sickle cell disease (sickle cell anemia, SCD anemia).

Compounds and methods for preventing and / or treating one or more symptoms of sickle cell diseases (SCD) by administering at least one of the compounds are provided. The compounds are chemically modified to increase bioavailability and activity, e.g., so that the compounds prevent adhesion and sickling of red blood cells (RBCs).

Embodiments herein provide specially designed synthetic BCL11A-targeting microRNAs for RNA polymerase II expression, and methods of use to treat hemoglobinopathies, such as sickle cell disease or thalassemia, by increasing the expression levels of fetal hemoglobin levels.