The Brigham and Women's Hospital, Inc.

Masanori Aikawa

Elena Aikawa

Claudia Goettsch

Tetsuro Miyazaki

Piero Ricchiuto

Hideo Yoshida

Iwao Yamada

Sasha Singh

Hiroshi Iwata

Joshua Daniel Hutcheson

Daiju Fukuda

Takuya Hara

Shunsuke Katsuki

Toshiaki Nakano

Maximillian Rogers

Sophie New

Kevin Croce

Shinsuke Ito

The present invention is directed to antibodies that interact with DLL4 and inhibit it from binding to NOTCH receptors. The invention also includes nucleic acids encoding the antibodies and methods of using the antibodies in research and in the prevention or treatment of various diseases and conditions.

Antibodies blocking DLL4-mediated notch signalling

Sortilin is a sorting receptor that directs target proteins to the secretary or endocytic compartments of cells that is found in both extracellular vesicles and cells. Provided herein are methods and compositions for decreasing or inhibiting trafficking of sortilin to an extracellular vesicle, for example by inhibiting the formation of intermolecular sortilin dimers.

Materials and methods for extracellular vessicle-associated diseases

The invention relates to compositions and methods for inhibiting macrophage activation via modulating PARP9 and/or PARP14 expression or activity, such as small molecules, RNAi and antibodies.

PARP9 and PARP14 as key regulators of macrophage activation

The invention relates to methods for decreasing, inhibiting, preventing, or reducing calcification by inhibiting sortilin 1.

Method for inhibiting calcification of a smooth muscle cell (SMC)

The present invention is directed to methods of treating or preventing nonalcoholic fatty liver disease by administering agents that inhibit the NOTCH signaling pathway. Antibodies that inhibit the binding of Delta like 4 ligand (Dll4) to NOTCH receptors may be used for this purpose.

Notch inhibition in the treatment and prevention of nonalcoholic fatty liver disease

Provided herein are methods for reducing levels of blood cholesterol, low-density lipoprotein (LDL), and/or the treatment of diseases associated with high cholesterol, hyperlipidemia, dyslipidemia, or high levels of low-density lipoprotein (LDL), wherein the methods comprise administering a DRP1 inhibitor to a subject in need thereof. In certain embodiments, the subject is selected for treatment as described herein when the subject exhibits intolerance to conventional statin therapy. Also contemplated herein are the use of DRP1 inhibitors in the treatment of cancer and inflammatory disease.

Modulation of PCSK9 and LDLR through DRP1 inhibition

The invention relates to compositions and methods for inhibiting macrophage activation via modulating PARP9 and/or PARP14 expression or activity, such as small molecules, RNAi and antibodies. Modulating the expression and/or activity of PARP9 and/or PARP14 allows the inhibition of monocytes or macrophage M1 activation and inflammation. Inhibiting undesirable excessive or sustained inflammation found in humans, for the treatment, prevention and/or management of conditions where undesirable excessive or sustained inflammation is known or likely to contribute to the onset, development and/or progression the conditions.

Method of inhibiting macrophage activation using an inhibitor of PARP9

Sortilin 1 is a novel inducer of vascular calcification

Disclosed herein are compositions and methods for treating soft-tissue calcification by targeting SLC25A24 and/or SLC25A3.

Mitochondrial phosphate carrier targets for treating soft-tissue calcification

Systems and methods for imaging of matrix vesicle-derived calcification are described. In one embodiment, the method comprises raising the pH of collagen stored in a solution, thereby causing the collagen to come out of the solution to form a network, adding matrix vesicles to the network, resulting in calcifications, and imaging the formation of the calcification. The calcification process can be imaged in real time by confocal or reflected light microscopy.

System and method for studying matrix vesicle calcification

The invention relates to methods for decreasing, inhibiting, preventing, or reducing matrix vesicle induced calcification by inhibiting the amount or formation of a complex comprising phosphatidylserine (PS), annexin II, annexin V or VI, and S100A9 or S100A12 in a macrophage.

Method for inhibiting calcification of a macrophage-derived matrix vesicle

The present invention is directed to methods of treating or preventing atherosclerosis and other cardiovascular diseases by administering agents that inhibit or modulate the NOTCH signaling pathway. In addition, the invention encompasses methods for assaying compounds for their ability to treat atherosclerosis based upon their effects on NOTCH signaling, and for measuring levels of amount, function, or activity of NOTCH pathway components in biological samples.

NOTCH inhibition in the treatment of cardiovascular disease

The present invention is directed to methods of treating or preventing a metabolic disease or disorder and cardiovascular complications and other complications thereof by administering agents that inhibit the NOTCH signaling pathway. In addition, the invention encompasses methods for determining whether a patient is at increased risk for developing these conditions by determining the amount, function, or activity of NOTCH pathway components in biological samples derived from the patient or in imaging analysis.

Growing community of inventors

Chestnut Hill, MA, United States of America

Masanori Aikawa