The General Hospital Corporation

The Brigham and Women's Hospital, Inc.

Other

Kenneth D Bloch

Warren M Zapol

Gregory D Cuny

Paul B Yu

Charles C Hong

Randall T Peterson

Donald B Bloch

Fumito Ichinose

Anthony Rosenzweig

Stefan Janssens

Christopher Newton-Cheh

Thomas J Wang

Akito Nakagawa

Francine E Lui

Revital Freedman

Pankaj Arora

D&eacute;sir&eacute; Collen

This invention relates to compounds of Formula I: (Formula I), and pharmaceutically acceptable salt thereof, which are allosteric effectors that increase the oxygen-being affinity of hemoglobin, which are useful in the treatment of sickle cell disease, high altitude tissue hypoxia, and other conditions. 

Heteroaryl disulfide compounds as allosteric effectors for increasing the oxygen-binding affinity of hemoglobin

The present invention relates to methods, kits and compositions to treat hypertension and other cardiovascular diseases in a subject, in particular, a method of treating or preventing a cardiovascular disease in a subject comprising administering to a subject at least one anti-miR agent to miRNA-425. In some embodiments, an anti-miR agent is a small molecule or an oligonucleotide complementary to at least part of the miR-425 of SEQ ID NO: 1, or an anti-miR complementary to at least part of the miRNA seed sequence AUGACA (SEQ ID NO: 2). Another aspect of the present invention relates to methods, kits and compositions to treat low blood pressure in a subject comprising administering a composition comprising a miR-425 agent to decrease ANP levels in the subject. Other aspects of the present invention relates to assays, methods and systems to identify a subject at risk of hypertension, or identifying a subject suitable to administration of an anti-miR-425 agent for treatment of hypertension, the assay comprising assessing if a subject is homozygous or heterozygous for the major (A) allele of rs5068 SNP, and/or assaying for levels of miR-425 and/or assaying for levels of NT-proANP and/or levels of ANP in the plasma of a subject.

Inhibitors of microRNAs that regulate production of atrial natriuretic peptide (ANP) as therapeutics and uses thereof

The present invention provides pyridinyl-substituted pyrazolyl pyrimidine small molecule inhibitors of bone morphogenetic protein (BMP) signaling having the structure of formula (I), wherein variables A, B, E, F, X, Y, Z, Ar, L, Rand Rare as defined in the specification. The compounds of the invention are useful in modulating cell growth, differentiation, proliferation, and apoptosis, and thus are useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation.

Inhibitors of the BMP signaling pathway

The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation.

Cloning and characterization of a full length cDNA encoding Sp110 (speckled 110), a novel 110 kDa polypeptide, is disclosed. It is disclosed that Sp110 is a component of the nuclear body, is expressed in leukocytes, and is also expressed in other types of cells, including endothelial cells, smooth muscle cells, liver cells and heart cells, after contact with certain cytokines. The disclosure also includes the following: Sp140 recruits Sp110 to the nuclear body, Sp110 functions as an activator of gene transcription, and Sp110 serves as a nuclear hormone receptor co-activator. Sp110 DNAs, polypeptides, antibodies are disclosed. Also disclosed are Sp110-related screening methods and clinical diagnostic methods.

Sp110, a polypeptide component of the nuclear body

Methods for reducing, partially preventing or completely preventing nitric oxide (NO) inhalation-related impairment of HPV in a mammal are disclosed. The methods include administering a therapeutically effective amount of NO by inhalation, and co-administering an effective amount of an anti-reactive oxygen species (anti-ROS) agent, e.g., N-acetyl-cysteine, or a leukotriene blocker. Methods for reducing, partially preventing or completely preventing loss of pulmonary vasodilatory responsiveness to NO inhalation in a mammal are also disclosed. The methods include administering a therapeutically effective amount of NO by inhalation, and co-administering an effective amount of an anti-ROS agent a therapeutically effective amount of a leukotriene blocker.

Enhancing therapeutic effectiveness of nitric oxide inhalation

A method for lessening or preventing non-pulmonary ischemia-reperfusion injury or inflammation in a mammal by identifying a mammal which has ischemia-reperfusion or is at risk for developing ischemia-reperfusion in a non-pulmonary tissue; and causing the mammal to inhale a therapeutically effective amount of gaseous nitric oxide sufficient to diminish the ability of leukocytes or platelets to become activated in a manner that contributes to an inflammatory process at the site of the ischemia-reperfusion or inflammation in the non-pulmonary tissue, thereby lessening or preventing non-pulmonary ischemia-reperfusion injury in the mammal.

Use of inhaled NO as anti-inflammatory agent

This invention relates to a gene therapy method for inducing pulmonary vasodilation. More specifically, this invention involves introducing the nitric oxide synthase gene into lungs resulting in pulmonary vasodilation. This results in a hypotensive effect in the pulmonary circulation which does not significantly affect systemic blood pressure or cardiac index. This method is useful to treat primary pulmonary hypertension or pulmonary hypertension secondary to various disease states.

Method of inducing vasodilation and treating pulmonary hypertension using adenoviral-mediated transfer of the nitric oxide synthase gene

Methods for reducing, partially preventing or completely preventing nitric oxide (NO) inhalation-related impairment of HPV in a mammal are disclosed. The methods include administering a therapeutically effective amount of NO by inhalation, and co-administering an effective amount of an anti-reactive oxygen species (anti-ROS) agent, e.g., N-acetylcysteine, or a leukotriene blocker. Methods for reducing, partially preventing or completely preventing loss of pulmonary vasodilatory responsiveness to NO inhalation in a mammal are also disclosed. The methods include administering a therapeutically effective amount of NO by inhalation, and co-administering an effective amount of an anti-ROS agent a therapeutically effective amount of a leukotriene blocker.

The present invention is directed to a leukocyte-specific gene Sp140 and its associated protein. Since it has structural analogies to other regulatory proteins and is localized in the nuclear body of certain cell types, Sp140 may be a transcription regulator involved in the body's interaction with viruses and in promyelocytic leukemia. The Sp140 gene can be used in gene therapy for treating certain viral diseases, autoimmune disorders and cancers, while the Sp140 protein may be useful as a diagnostic and prognostic marker in the analysis of certain autoimmune disorders.

Leukocyte-specific protein and gene, and methods of use thereof

Disclosed are methods of treating, inhibiting or preventing vascular thrombosis or arterial restenosis in a mammal. The disclosed methods include causing the mammal to inhale a therapeutically-effective concentration of gaseous nitric oxide (NO). Also disclosed are methods that include the administration of the following types of agents in conjunction with inhaled nitric oxide: compounds that potentiate the beneficial effects of inhaled nitric oxide, and antithrombotic agents that complement or supplement the beneficial effects of inhaled nitric oxide.

Growing community of inventors

Brookline, MA, United States of America

Kenneth D Bloch