Materials and methods for treating a patient with a hemoglobinopathy, both ex vivo and in vivo, and materials and methods for creating permanent changes to the genome that can result in at least one deletion, insertion, modulation, or inactivation of a transcriptional control sequence of a BCL11A gene in a cell by genome editing.

Materials and methods for treating a patient with a hemoglobinopathy, both ex vivo and in vivo, and materials and methods for creating permanent changes to the genome that can result in at least one deletion, insertion, modulation, or inactivation of a transcriptional control sequence of a BCL11A gene in a cell by genome editing.

A compound of the following general formula [I]:

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wherein each symbol has the same meaning as defined herein, or a pharmaceutically acceptable salt thereof, or a solvate thereof, and a pharmaceutical use of the same in treating organ transplant rejection, graft versus host reaction after transplantation, autoimmune disease, allergic disease and chronic myeloproliferative disease.

The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ALAS1 gene, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of ALAS1.

Methods and compositions for improved clinical outcomes for trauma patients receiving whole blood transfusion. Methods and compositions for improved clinical outcomes for blood transfusions for cancer patients are also provided.

Methods and compositions for improved clinical outcomes for trauma patients receiving whole blood transfusion. Methods and compositions for improved clinical outcomes for blood transfusions for cancer patients are also provided.

The present invention relates to a film-coated swallowable tablet comprising eltrombopag bis(monoethanolamine) and pharmaceutically acceptable excipients comprising calcium silicate as diluent. The invention further relates to the use of said tablet as a medicament, particularly in the treatment of immune thrombocytopenia (ITP), thrombocytopenia in patients with chronic hepatitis C virus (HCV) and severe aplastic anaemia (SAA).

The present invention is directed to a compound of Formula (I) or a pharmaceutically acceptable salt thereof. Compounds of Formula (I) are CD38 inhibitors, which can be used to treat a disease or condition in a subject that benefits from an increase in NAD.sup.+ or to treat a mitochondrial disorder in a subject. Such disease or condition is a muscle structure disorder, a neuronal activation disorder, a muscle fatigue disorder, a muscle mass disorder, a metabolic disease, a cancer, a vascular disease, an ocular vascular disease, a muscular eye disease, or a renal disease. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 30 to 135; examples 1 to 61; table). Such an exemplary compound is e.g. N-((1r,4r)-4-(2-methoxyethoxy) cyclohexyl)-5-(thiazol-5-yl)-1H-indole-7-carboxamide (II).

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Antibodies to the enzyme matriptase-2 (MTP-2) are presented. Inhibiting MTP-2 reduces uptake of dietary iron and reduces the release of iron from cellular stores in the body. Inhibitors of MTP-2 (such as antibodies to the serine protease domain) can be used to treat iron overload, which is a feature of diseases such as beta-thalassaemia and which otherwise leads to toxic accumulation of iron. Combination of an MTP-2 inhibitor with an activin receptor ligand trap, or with erythropoietin, provides additional therapeutic effects.

Embodiments of the disclosure encompass methods and compositions related to overcoming or preventing cancer resistance to anti-apoptotic proteins, for example BH3 mimetics. The disclosure provides methods for modulating p73 to reduce cancer resistance to BH3 mimetics including inhibitors of Bcl-2, Bcl-xL, Mcl-1, Bcl-W, A1/BFL-1, or a combination thereof. In specific embodiments, targeting isoforms of p73, such as TAp73 or DNp73, results in reduction of cancer resistance to BH3 mimetics to allow effective treatment of hematological cancers.