17 results about "Sickle Cell Diseases" patented technology

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.

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.

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.

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.

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.

326 Abstract of the Disclosure The present invention features compositions and methods for editing deleterious mutations associated with hemoglobinopathies, such as sickle cell disease (SCD). In particular embodiments, the invention provides methods for correcting mutations in a beta globin 5 polynucleotide using modified adenosine base editors termed “ABE8” having unprecedented levels (e.g., >60-70%) of efficiency. 326 20 26 20 47 29 18 J un 2 02 6 1 8 J u n 2 0 2 6 2 0 2 6 2 0 4 7 2 9 3 2 6

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

The present invention relates to a treatment of vaso-occlusive crisis (VOC) associated with Sickle cell disease by administering a therapeutically effective amount of 4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl) propanoate.

The invention relates to a new process for preparing compounds of the formula (I) and pharmaceutically acceptable salts thereof, which act as ferroportin inhibitors being suitable for the use as medicaments in the prophylaxis and / or treatment of diseases caused by a lack of hepcidin or of iron metabolism disorders leading to increased iron levels or increased iron absorption, including iron overload, thalassemia, sickle cell disease and hemochromatosis.

Provided herein are compositions and methods comprising a purified hemoglobinase enzyme, or fragments thereof, and their use to treat Sickle Cell Disease (SCD) and / or one or more diseases associated with vaso-occlusive crises and / or thrombosis.

Provided herein, inter alia, are conjugates comprising a targeting agent (e.g., a hematopoietic cell (e.g., erythroid precursor cell) targeting agent) comprising a protein (e.g., an antibody) that specifically binds to the transferrin receptor (TFR) (e.g., human TFR (hTFR) (e.g., hTFR1)); (b) at least one oligonucleotide operably linked to (b) at least one oligonucleotide that modulates the expression and / or activity of a target gene, nucleic acid (e.g., mRNA) and / or protein expressed by a target cell; as well as methods of making the conjugates and pharmaceutical compositions comprising the conjugates. Further provided herein are methods of utilizing the conjugates, including, for example, methods of treating hemoglobinopathy (e.g., sickle cell disease (SCD) or thalassemia (e.g., alpha-thalassemia, beta-thalassemia, delta-thalassemia, or gamma-thalassemia)).

The present disclosure provides nucleic acids, compositions and vectors containing and their use for effecting gene editing and / or gene expression alteration on sickle cell disease (SCD)-associated genes invivo. The present disclosure further provides methods of effecting gene editing and / or gene expression alteration on SCD-associated genes invivo and methods of preventing, ameliorating, or treating SCD.

To provide: methods of increasing levels of fetal hemoglobin (HbF) in cells; and 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-thalassemia.SOLUTION: A method for increasing expression of a fetal hemoglobin (HbF) in a eukaryotic cell comprises contacting the cell with an inhibitor of a target protein or target protein complex that serves to regulate HbF expression. Optionally, the target protein is Cullin 3 (CUL3) or Speckle-type POZ protein (SPOP).SELECTED DRAWING: Figure 1

This invention relates to substituted pyrazolopiperidine carboxylic acids, their salts and methods of preparation thereof, and also to their use in the preparation of medicaments for the treatment and / or prevention of diseases, particularly cardiovascular and cardiac diseases, preferably heart failure with reduced and preserved ejection fraction (HFrEF, HFmrEF and HFpEF), hypertension (HTN), peripheral artery disease (PAD, PAOD), cardiorenal and renal diseases, preferably chronic kidney disease and diabetic kidney disease (CKD and DKD), cardiopulmonary and pulmonary diseases, preferably pulmonary hypertension (PH) and other diseases, preferably neurodegenerative diseases and different forms of dementia, fibrotic diseases, systemic sclerosis (SSc), sickle cell disease (SCD), and wound healing disorders such as diabetic foot ulcers (DFU).

The present disclosure provides nucleic acids, compositions and vectors containing and their use for effecting gene editing and / or gene expression alteration on sickle cell disease (SCD)-associated genes, e.g., in vivo. The present disclosure further provides compositions for and methods of effecting gene editing and / or gene expression alteration, such as on SCD-associated genes in vivo, and methods of preventing, ameliorating, or treating SCD.

Provided herein, in particular, are a conjugate comprising a protein (e.g., an antibody) that specifically binds to a transferrin receptor (TFR) (e.g., human TFR (hTFR) (e.g., hTFR1)), wherein the conjugate comprises (b) a conjugate operably linked to at least one oligonucleotide that modulates the expression and / or activity of a target gene, target nucleic acid (e.g., mRNA) and / or target protein expressed by the target cell, as well as a method for producing the conjugate and a pharmaceutical composition comprising the conjugate. Furthermore, provided herein are methods of using the conjugate, including, for example, a method for treating hemoglobin disorders (e.g., sickle cell disease (SCD)) or thalassemia (e.g., α-thalassemia, β-thalassemia, δ-thalassemia, or γ-thalassemia).