Baltimore Highlands, MD, United States
Baltimore Highlands, MD, United States

Time filter

Source Type

Johns Hopkins University, Kennedy Krieger Institute and U.S. National Institutes of Health | Date: 2014-04-28

The present invention provides novel hydrogels through peptides, which are designed to self-assemble and produce magnetic resonance (MR) contrast through chemical exchange saturation transfer (CEST). The location and integrity of these gels could consequently be tracked using MR imaging. The self-assembly of the peptides into hydrogels can be brought about by a change in pH, ionic strength, temperature, and concentration of ions.

Johns Hopkins University and Kennedy Krieger Institute | Date: 2014-12-03

The present invention relates to the field of stem cells. More specifically, the present invention provides methods and compositions useful for the highly efficient conversion of human stem cells to lineage-specific neurons. In a specific embodiment, a method of inducing differentiation of human stem cells into dopaminergic (DA) neurons comprises the steps of (a) transfecting human stem cells with a lentiviral vector encoding Atoh1, wherein the vector is Dox inducible; and (b) growing the transfected cells in culture in the presence of Dox, Sonic Hedgehog (SHH) and FGF-8b until DA neurons are induced.

An embodiment in accordance with the present invention provides a new MRI method to image the buildup of exchange transfer processes from nuclei in mobile solute molecules in tissue via another molecule (e.g. solvent such as water). The pulse sequence can detect Chemical Exchange Saturation Transfer (CEST), relayed Nuclear Overhauser Enhancement (rNOE) CEST, and selective induced exchange transfer processes. Further, the proposed MRI pulse sequence involves acquiring two or more images with a difference in waiting period (delay) after a radiofrequency excitation, saturation pulse, or series of such pulses. This produces a series of exchange transfer images sensitive to the speed of transfer of changes in magnetization. Subtracting two images or fitting a time series produces maps with minimum interference from direct water saturation and from semi-solid magnetization transfer and other fast exchanging protons.

Johns Hopkins University and Kennedy Krieger Institute | Date: 2013-04-17

The present invention includes drug-loaded, polymer nanoparticles and liposomes further incorporating a non-paramagnetic, bioorganic CEST agent. The CEST agent allows for an alternative approach to accomplish MR-compatible in vivo tracking of drug-loaded polymer nanoparticles and liposomes, including simultaneous multi-color mapping of more than one particle type, or of the same particle type delivered via two different routes (e.g., systemic versus local). Additionally, the present invention can include a library of biodegradable diamagnetic (DIA)CEST agents. These DIACEST agents can be incorporated into nanoparticle-based delivery systems, such as stealth liposomes loaded with doxorubicin and stealth polymer nanoparticles loaded with paclitaxel. These systems can be tracked, according to an embodiment of the present invention using CEST-based MRI (compared to SPECT/CT) as a method to monitor the efficiency with which the nanoparticles reach the targeted tumors and how long they persist. Measured particle persistence times are also used to guide the spacing between doses.

Johns Hopkins University, Kennedy Krieger Institute and Duke University | Date: 2014-04-16

The present invention relates to the fields of neurological and skin disorders. More specifically, the present invention provides methods and compositions for diagnosing and prognosing Sturge-Weber Syndrome (SWS), Klippel-Trenaunay-Weber Syndrome (KTWS), and Port Wine Stains (PWS). In one embodiment, a method for prognosing or monitoring treatment of a patient with SWS, KTWS and/or PWS comprises the steps of (a) providing a sample from the patient undergoing treatment; (b) determining the number of alleles in the sample comprising at least one activating somatic mutation in the guanine nucleotide-binding protein G subunit alpha (GNAQ) gene or protein; (c) comparing the number of alleles comprising the at least one somatic mutation to the number of alleles comprising the somatic mutation from a patient sample provided prior to undergoing treatment; and (d) determining that the patient is improving if there is a decrease in the number of alleles comprising the at least one somatic mutation from the sample of step (a).

The present invention provides a novel approach for CEST MR imaging, called Multi-echo Length and Offset VARied Saturation (Me-LOVARS) CEST. This method allows efficient collection of additional CEST data without penalty in scan time, which could be useful for enhancing the contrast, increasing the specificity or improving quantification of exchange. As CEST-MRI has shown promise at both the pre-clinical and clinical levels, including for detecting and grading brain tumors and evaluating ischemia, using either endogenous CEST contrast or through administration of CEST contrast agents. This fast and robust imaging method is suitable for accelerating image collection and widening the scope of applications for CEST-MRI.

Compositions and methods for treatment of Sturge-Weber Syndrome, Klippel-Trenaunay-Weber Syndrome, Port-Wine Stains and related neurocutaneous disorders are provided. Cell lines having the somatic mutation GNAQ p.Arg183Gln amino acid substitution, which was found to be the cause of port-wine stains (prevalence 1 in 300) and Sturge-Weber syndrome are also provided. Compositions and methods for treatment of uveal melanoma are also provided herein. Methods of screening novel compounds and compositions useful in increasing RGS2 and/or RGS4 expression and function in vitro, and for treatment of Sturge-Weber Syndrome, Klippel-Trenaunay-Weber Syndrome, Port-Wine Stains and related neurocutaneous disorders are provided are also provided.

An embodiment in accordance with the present invention provides a new acquisition scheme for T2-weighted BOLD fMRI. It employs a T2 preparation module to induce the BOLD contrast, followed by a single-shot 3D fast gradient echo (GRE) readout with short echo time (TE<2 ms). The separation of BOLD contrast generation from the readout substantially reduces the dead time due to long TE required in spin echo (SE) BOLD sequences. This approach termed 3D T2prep-GRE, can be implemented with any magnetic resonance imaging machine, known to or conceivable by one of skill in the art. This approach is expected to be useful for ultra-high field fMRI studies that require whole brain coverage, or focus on regions near air cavities. The concept of using T2 preparation to generate BOLD contrast can be combined with many other fast imaging sequences at any field strength.

Leung D.G.,Kennedy Krieger Institute
Annals of neurology | Year: 2013

The muscular dystrophies comprise a heterogeneous group of genetic disorders that produce progressive skeletal muscle weakness and wasting. There has been rapid growth and change in our understanding of these disorders in recent years, and advances in basic science are being translated into increasing numbers of clinical trials. This review will discuss therapeutic developments in 3 of the most common forms of muscular dystrophy: Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. Each of these disorders represents a different class of genetic disease (monogenic, epigenetic, and repeat expansion disorders), and the approach to therapy addresses the diverse and complex molecular mechanisms involved in these diseases. The large number of novel pharmacologic agents in development with good biologic rationale and strong proof of concept suggests there will be an improved quality of life for individuals with muscular dystrophy. Copyright © 2013 American Neurological Association.

Li Y.,Kennedy Krieger Institute | Laterra J.,Kennedy Krieger Institute
Cancer Research | Year: 2012

The origins of tumor-propagating neoplastic stem-like cells [cancer stem cells (CSC)] and their relationship to the bulk population of tumor cells that lack stem-like tumor-propagating features (i.e., transit-amplifying cancer progenitor cells) remain unclear. Recent findings from multiple laboratories show that cancer progenitor cells have the capacity to dedifferentiate and acquire a stem-like phenotype in response to either genetic manipulation or environmental cues. These findings suggest that CSCs and relatively differentiated progenitors coexist in dynamic equilibrium and are subject to bidirectional conversion. In this review, we discuss emerging concepts regarding the stem-like phenotype, its acquisition by cancer progenitor cells, and the molecular mechanisms involved. Understanding the dynamic equilibrium between CSCs and cancer progenitor cells is critical for the development of therapeutic strategies to deplete tumors of their tumor-propagating and treatment-resistant cell subpopulations. ©2012 AACR.

Loading Kennedy Krieger Institute collaborators
Loading Kennedy Krieger Institute collaborators