72 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.

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.

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 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.

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.

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.

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).

The present disclosure relates to the use of MASP-2 inhibitors and / or MASP-3 inhibitors and compositions comprising the same for treatment of sickle cell disease, including treatment, reduction, and / or prevention of sickle cell disease symptoms or manifestations.

We disclose here the nano-enabled delivery of highly potent 5-hydroxymethyl furfural (5-HMF) to sickled blood cells in patients. 5-HMF, a superior antisickling agent, has been formulated to address the limitations of existing treatment modalities arising from disfavorable pharmacokinetics of the drug compound. Specifically, two complementary 5-HMF prodrugs are integrated as a ‘protected’ biocompatible composite nanoparticle designed to readily fuse with RBCs and be amenable to transdermal delivery (5-HMF-grafted-phospholipid layered over a sucrose-derived graphitic carbon dot core). These RBC-targeted, protected, biocompatible, self-assembled 5-HMF prodrug nanoparticles for sickle cell disease are the first in class technology for offering a treatment for sickle cell disease which has improved potency, targeted payload delivery, and extended release with the red blood cells with enhanced pharmacodynamic effect in a treated patient.

Compositions for identifying a pathogenic bacterial infection include a mannitol compound with one or more substituents including radioisotopes. These radiopharmaceuticals, such as a positron-emitting mannitol analogue, [18F]fluoromannitol ([18F]FMtl), are rapidly taken up by gram-positive and gram-negative bacteria such as E. coli, S. aureus, A. baumannii, S. epidermis, P. mirabilis, S. enterica, K. pneumonia, E. faecium, E. cloacae, and M. marinum, but not non-active infection sites such as sterile inflammatory sites, cancer sites, etc. Administration of these radiopharmaceuticals to and subsequent imaging of patients, e.g., via positron emission tomography (PET), enables detection of deep-seated and difficult to manage bacterial infections, such as osteomyelitis and prosthetic joint infection, or in patients with sickle cell disease. [18F]FMtl injection detects and differentiates infection rapidly. The radiolabeled mannitol compounds can be produced via nucleophilic substitution reactions that are deployable on commercially available synthesizers, facilitating straightforward and wide accessibility, and counteracting unnecessary antibiotic use.

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.

Provided herein are methods of treating sickle cell disease, methods of increasing hemoglobin levels in a subject diagnosed with sickle cell disease, and methods of reducing hemolysis-associated complications in a subject diagnosed with sickle cell disease, together with kits for such treatments, in a subject in need thereof, comprising administering a Gardos channel inhibitor such as 2,2-bis(4-fluorophenyl)-2-phenylacetamide and a pyruvate kinase activator such as N-(4-((4-(Cyclopropylmethyl)-1-piperazinyl)carbonyl)phenyl)-8- quinolinesulfonamide to the subject. Subjects eligible for treatment include subjects as having hemolysis dominant (HD) sickle cell disease on the basis of laboratory markers, clinical history, and / or sequelae.

Disclosed herein are antibody-oligonucleotide conjugates, pharmaceutical compositions, and methods for treating Sickle Cell Disease. The disclosure contemplates compositions and methods capable of binding a human hematopoietic stem cell marker conjugated to an oligonucleotide capable of hybridizing a target sequence. In some embodiments, the target sequence is a BCL11A transcript sequence. In some embodiments of the disclosure, the antibody-oligonucleotide conjugate promotes antisense- and / or RNA interference-mediated inhibition of BCL11A.

The present invention involves the use of Caspase-1 inhibitors for treating ineffective erythropoiesis in patients with sickle cell disease (SCA). It highlights increased levels of IL-18 positive cells and Caspase-1 activity in hematopoietic stem cells (HSCs) of SCA patients compared to healthy donors. The invention demonstrates that treatment with a Caspase-1 inhibitor reduces this activity, suggesting its potential therapeutic benefit.

The present application 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 and a method for transducing hematopoietic stem cells. The present application 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; further provided is a method for transducing hematopoietic stem cells with lentivirus, which is simple to operate, can maintain the long-term stemness of hematopoietic stem cells in vitro, can realize efficient and stable transduction of hematopoietic stem cells, and the transduction rate is greater than 90%. The hematopoietic stem cells transduced by the lentivirus transduction method of the present application can be used for hematopoietic stem cell gene therapy of hematopoietic system genetic diseases, such as severe combined immunodeficiency, beta-thalassemia and sickle cell disease, Wiskott-Aldrich syndrome, and has a good application prospect.

The present disclosure relates to methods for treating or preventing or delaying progression or reducing or inhibiting or hindering development of a complication associated with sickle cell disease in a subject suffering from sickle cell disease, the method comprising administering to the subject a compound that inhibits granulocyte colony stimulating factor (G-CSF) signaling and / or G-CSF activity.

The present invention provides compositions used for the treatment and / or prevention of protein aggregation disorders. [Solution] Proteopathy encompasses a wide range of ailments, including neurodegenerative diseases (e.g., polyglutamine diseases such as huntingtin in Alzheimer's disease, Parkinson's disease, and Huntington's disease, and prion diseases); amyloidosis of other non-neuronal proteins (especially I1-antitrypsin, immunoglobulin light and heavy chains, lactadherin, apolipoprotein, gelzolin, lysozyme, fibrinogen, atrial natriuretic factor, keratin, lactoferrin, and β-2 microglobulin, etc.); sickle cell disease; cataracts; cystic fibrosis; retinitis pigmentosa; and nephrogenic diabetes insipidus. Administration of sulfatase inhibitors is generally suitable for treating and / or preventing protein toxicity associated with proteopathy. Therefore, the present invention provides compositions comprising sulfatase inhibitors for the treatment of proteopathy.

The invention provides a guide RNA [gRNA], a kit, a composition, and a method for detecting genetic variations such as Sickle Cell Disease (SCD) and identifying carriers through an optimized point-of-care CRISPR-based assay. The gRNA detects SCD-specific nucleotide changes using distinct mixes for Haemoglobin A (HbA) and Haemoglobin S (HbS). The guide RNA with a plurality of SNP recognition sites is constructed through the mediation of hybridization chain reaction, where a plurality of Cas12b protein is combined. The guide RNA disclosed herein is capable of determining the wildtype, homozygous or heterozygous (carrier) state of sickle cell disease.

Disclosed herein are methods of expanding hematopoietic stem cells (HSC) ex vivo and their uses thereof, the methods comprising administrating a radical trapping antioxidant (RTA) to the HSC isolated from a subject, wherein the RTA blocks ferroptosis in the HSC and increases HSC expansion. Also disclosed herein are methods of treating blood disorders, such as, for example, sickle cell disease or β-thalassemia. Further disclosed is a kit for use of HSC expansion.

Sickle cell disease (SCD) is a single gene disorder characterized by mutant hemoglobin-S (HbS) and chronic intravascular haemolysis. Painful vaso-occlusive crises (VOC) are typical of SCD and often associated to a further rise in hemolysis. VOC is the clinically painful form of vaso-occlusion, that is due to the aggregation of red blood cells in the capillaries and venules. Such event is promoted or aggravated by adhesion of polymorphonuclear neutrophils (PMNs) to red blood cells and the endothelium leading to tissue ischemia, inflammation and imperfect repair. Repeated vaso-occlusion and PMNs interactions with the vascular endothelium are thought to promote microvascular injuries in SCD patients. The inventors tested the effect of pharmacological inhibition of TREM-1 with LR12 peptide in two experimental vaso-occlusive crisis models. Additional validation of TREM-1 involvement in vaso-occlusion was verified using mice with sickle cell disease and Trem-1 gene deficiency. In particular, the inventors showed that TREM-1 inhibition is particular suitable for limiting the severity of vaso-occlusions. The results obtained by the inventors also suggest that plasmatic concentration of sTREM-1 could be a reliable biomarker for predicting vaso-occlusions and / or SCD-associated organ dysfunction and end-organ damage.