35 results about "Hemoglobinopathy" patented technology

The present invention is directed to the use of immunomodulatory compounds, particularly members of the class of compounds known as IMiDs™, and more specifically the compounds 4-(Amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione and 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione, to induce the expression of fetal hemoglobin genes, genes essential for erythropoiesis, and genes encoding alpha hemoglobin stabilizing protein, within a population of CD34⁺ cells. These compounds are used to treat hemoglobinopathies such as sickle cell anemia or β-thalassemia, or anemias caused by disease, surgery, accident, or the introduction or ingestion of toxins, poisons or drugs.

The invention relates to methods and uses of modulating fetal hemoglobin expression (HbF) in a hematopoietic progenitor cells via inhibitors of BCL11A expression or activity, such as RNAi and antibodies.

The invention relates to methods of using compositions comprising EPO-mimetic peptides to treat anemia. The invention relates to methods of treating disorders characterized by the insufficient amounts of erythrocytes and hemoglobulin in the blood due to myelodysplastic syndrome (MDS) or by hemoglobinopathies, such as alpha- or beta-thalessemia or sickle cell disease.

Compositions and methods of treating anemia, cancer, AIDS, or severs beta -chain hemoglobinopathies by administering a therapeutically effective amount of phenylacetate or pharmaceutically acceptable derivatives thereof or derivatives thereof alone or in combination or in conjunction with other therapeutic agents. Pharmacologically-acceptable salts alone or in combinations and methods of preventing AIDS and malignant conditions, and inducing cell differentiation are also aspects of this invention.

Retroviral gene therapy vectors that are optimized for erythroid specific expression and treatment of hemoglobinopathic conditions are disclosed.

This disclosure provides compositions and methods for improving erythrocyte dysfunction or treating a hemoglobinopathy or a thalassemia (e.g., sickle cell disease or β-thalassemia).

Methods of using one or more fumaric acid esters or pharmacologically active salts, derivatives, analogues, or prodrugs thereof to increase expression of fetal hemoglobin (HbF) are disclosed. The methods typically include administering to a subject an effective amount of one or more fumaric acid esters optionally in combination or alternation with hydroxyurea to induce HbF expression in the subject in an effective amount to reduce one or more symptoms of a sickle cell disorder, a hemoglobinopathy, or a beta-thalassemia, or to compensate for a genetic mutation is the human beta-globin gene (HBB) or an expression control sequence thereof. Pharmaceutical dosage units and dosage regimes for use in the disclosed methods are also provided.

Substituted benzimidazole and 3H-imidazo[4,5-b]pyridines or formula I: where X and Y respectively are selected from: (i) N and N; and (ii) N and CR⁴; A² is selected from: a C₅ heteroarylene group, containing 2 or 3 ring heteroatoms, where the bonds to L1 and the core are β to one another; L¹ is selected from: (i) ^A1—O—CH₂—^A2; (ii) ^A1—CH₂—O—^A2; (iii) ^A1—C(═O)—NH—^A2; (iv) ^A1—CH(OH)—^A2; (v) ^A1—CH₂—NH—C(═O)—^A2; (vi) ^A1—S—CH₂—^A2; (vii) ^A1—CH₂—S—^A2; (viii) ^A1—CH₂—^A2; and (ix) ^A1—CH(CH₃)—O-^A2; A1 is phenyl, optionally substituted by F or CF₃; their use as pharmaceuticals, and in particular, in treating cancer and hemoglobinopathies.

The presently disclosed subject matter provides for expression cassettes that allow for expression of a globin gene or a functional portion thereof, vectors comprising thereof, and cells transduced with such expression cassettes and vectors. The presently disclosed subject matter further provides methods for treating a hemoglobinopathy in a subject comprising administering an effective amount of such transduced cells to the subject.

Recombinant lentiviral vectors having a region encoding a functional β-globin gene; and large portions of the β-globin locus control regions which include DNase I hypersensitive sites HS2, HS3 and HS4 provides expression of β-globin when introduced into a mammal, for example a human, in vivo. Optionally, the vector further includes a region encoding a dihydrofolate reductase. The vector may be used in treatment of hemoglobinopathies, including β-thalessemia and sickle-cell disease. For example, hematopoietic progenitor or stem cells may be transformed ex vivo and then restored to the patient. Selection processes may be used to increase the percentage of transformed cells in the returned population. For example, a selection marker which makes transformed cells more drug resistant than un-transformed cells allows selection by treatment of the cells with the corresponding drug.

The present disclosure provides improved genome editing compositions and methods for editing a BCL11A gene. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of a hemoglobinopathy.

The invention relates to method of treating or inhibiting progression of hemoglobinopathy in a subject in need thereof comprising inhibiting interaction between LRF-BTB and CHD protein-LBD.

The present disclosure provides improved multiplex genome editing compositions and methods. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of a hemoglobinopathy, a cancer, an infectious disease, an autoimmune disease, an inflammatory disease, or an immunodeficiency.

A DNA construct containing an erythroid lineage-specific promoter operably linked to a nucleotide coding sequence of interest and a method of using the same in the prevention or treatment of a hematopoietic disorder such as a hemoglobinopathy are described. Further disclosed are erythroid-specific promoters and erythroid-specific enhancers that can be used in the DNA construct.

The present invention provides an assay, suitable for neonatal screening of hemoglobinopathies by quantitatively determining the presence of at least one pair of hemoglobin (Hb) variants, determining the ratio between the signals obtained from each variant; and, based on that ratio, determining whether the tested subject is afflicted or not.

The present invention provides compounds (such as compounds of formula I-a) that induce γ globin expression and pharmaceutical compositions thereof. Such compounds may have beneficial therapeutic effects. Compounds and compositions described herein may be used to treat hemoglobinopathies such as β-thalassemia and sickle cell anemia. (I-a)