Texas Children's Hospital

Other

Marval Pharma, Inc.

Marval Biosciences, Inc.

Alzeca Biosciences, LLC

University of Texas System

Case Western Reserve University

Baylor College of Medicine

Cleveland State University

Texas Heart Institute

Sensulin, LLC

University of Houston System

Texas Children's Hosptial

Tanifum, Eric A.

Srivastava, Mayank

Ananth V Annapragada

Eric A Tanifum

Ravi Bellamkonda

Mayank Srivastava

Indrani Dasgupta

Russell M Lebovitz

Chandra Vijayalakshmi

Efstathios Karathanasis

Stephen C Cook

Eric A Hoffman

Jason Eriksen

Mostafa Analoui

Ketankumar B Ghaghada

Carlo Medici

Ronald J Biediger

James T Willerson

Robert V Market

Peter Vanderslice

Darren G Woodside

Vikas Kundra

James A Bankson

Chen-Yu Kao

Anil Shetty

Zbigniew Starosolski

Qingshan Mu

Richard Dixon

Eric Hoffman

Xianwei Sun

Ketan B Ghaghada

Murali K Ravoori

Parag Parekh

Eric Tanifum

Jason L Eriksen

Methods and compositions for detecting tau pathology are described. The compositions for detecting tau pathology comprise a targeting ligand that specifically binds to a cell surface marker of tau pathology, wherein the targeting ligand is linked to a liposome that includes an imaging agent. The compositions can be used in a method for imaging tau pathology in a subject that comprises administering to the subject an effective amount of the composition to a subject and imaging at least a portion of the subject to determine if that portion of the subject exhibits tau pathology. The compositions can also be used to detect tau pathology in biological samples obtained from a subject.

Targeting ligands for tau pathology

Provided herein are nanoparticle-based gadolinium (Gd) agents which may be used, e.g., in T1-weighted MR imaging (MRI). In various embodiments, dual-Gd liposomal agents are provided which contain both core-encapsulated Gd as well as surface-conjugated Gd. In various embodiments, these agents were observed to deliver a higher concentrations of Gd and result in substantial improvements in signal to noise ratios and contrast to noise ratios. Also provided are methods for in vivo imaging and/or treating diseases such as cancer or tumor in a subject.

Dual mode gadolinium nanoparticle contrast agents

A liposomal composition ('ADx-003') is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I: wherein X is &#x2014;CH&#x2014;, &#x2014;CH&#x2014;CH&#x2014;, &#x2014;CHO&#x2014;, or &#x2014;O&#x2014;CO&#x2014;; Y is &#x2014;CH&#x2014;CH&#x2550;CH&#x2014; or A and B are independently selected from C and N; R, R, R, and Rare independently selected from &#x2014;H, halogen, &#x2014;OH, and &#x2014;CH; and R, R, and Rare independently selected from &#x2014;H, halogen, &#x2014;OH, &#x2014;OCH, &#x2014;NO, &#x2014;N(CH), C-Calkyl, or a substituted or unsubstituted C-Caryl group, except that when A and/or B is N the adjacent Rand/or Ris &#x2014;H, or a pharmaceutically acceptable salt thereof.

Targeted contrast agents for MRI of alpha-synuclein deposition

Disclosed herein is a composition comprising a plurality of liposomes having an average diameter of less than 400 nanometers, wherein the plurality of liposomes comprise: a first lipid or phospholipid; a second lipid or phospholipid which is derivatized with a polymer; and a sterically bulky excipient capable of stabilizing the liposomes; a third lipid or phospholipid derivatized with a polymer terminated with an integrin targeting component; DSPE or a fourth lipid or phospholipid derivatized with a group binding a contrast enhancing agent wherein the plurality of liposomes optionally encapsulates a payload component consisting of one or more bioactive agents.

Targeting nanoparticles

Readily available hydrophilic and small organofluorine moieties were condensed via 'click chemistry' to generate nonionic hydrophilic fluorinated molecules with uniqueF MR signatures. These were used to fabricate stable liposome formulations for imaging various tissue types. This approach was tailored to exploit the broad spectrum of organicF molecular species and to generate probes with distinctF MRI signatures for simultaneous assessment of multiple molecular targets within the same target volume.

Hydrophilic fluorinated molecules for liposomal 19F MRI probes with unique MR signatures

Provided are aromatic compounds, phospholipid-polymer-aromatic conjugates comprising the aromatic compounds, and liposome compositions including the phospholipid-polymer-aromatic conjugates. The liposomal compositions may be useful for imaging of Alzheimer's Disease, for example, imaging of the amyloid-&#x3b2; plaque deposits characteristic of Alzheimer's Disease.

MRI imaging of amyloid plaque using liposomes

A liposomal composition ('ADx-001') is provided, ADx-001 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand. The macrocyclic gadolinium-based imaging agent may be conjugated to a fourth phospholipid.

Targeted contrast agents for MRI of amyloid deposition

The present invention is directed towards new chemical entities based on a lipid-paramagnetic metal ion chelate. The lipid portion of the compound intercalates into the membrane of a liposome. The compounds of the invention find particular use as paramagnetic contrast media for magnetic resonance imaging. It has been surprisingly discovered that the liposomal contrast media do not substantially cross the placental barrier into the vasculature of the fetus(es) when administered to a pregnant subject. These novel compounds are useful in the diagnosis of disorders and diseases in both gravid and non-gravid subjects. The invention is also directed towards pharmaceutical compositions comprising these compounds and the uses of these compounds.

Liposomal gadolinium (GD) contrast agent 'NMRX' for T1-MRI

Methods and compositions are provided for objectively characterizing a pathological lesion in a patient. The method comprises: introducing into the patient a contrast enhancing agent; subjecting the patient to magnetic resonance imaging to obtain an image; and applying a 3-D autocorrelation function to a subdomain of interest of the image to obtain at least one 3-D autocorrelation spectrum. The method may further comprise comparing the at least one 3-D autocorrelation spectrum to a pre-existing 3-D autocorrelation spectrum that is characteristic for the pathological lesion. In one example, the methods and compositions may be useful for identifying and objectively characterizing amyloid plaque deposits characteristic of Alzheimer's Disease.

Methods and compositions for objectively characterizing medical images

Lipid-based nanoparticle compositions are provided. The compositions generally comprise lipid-hydrophilic polymer-amyloid binding ligand conjugates, and may be liposomal compositions. The compositions, including the liposomal compositions, may be useful for imaging and/or the treatment of amyloid-&#x3b2; plaque deposits characteristic of Alzheimer's Disease.

Lipid-based nanoparticles

Vesicle compositions are provided that comprise a therapeutic compound. The vesicle compositions may be capable of releasing the therapeutic compound in response to the presence of an external trigger. The vesicle compositions may comprise a plurality of biocompatible vesicles. The biocompatible vesicles may comprise a therapeutic compound for treatment of a patient in need thereof, and one or more cross-linkages between two or more of the biocompatible vesicles, each cross-linkage comprising a chemical sensing moiety and a sensed moiety. In some embodiments, the therapeutic compound may be any compound that provides palliative, curative, or otherwise beneficial effects to a patent.

Vesicle compositions

Growing community of inventors

Manvel, TX, United States of America

Ananth V Annapragada