Washington University

Disarm Therapeutics, Inc.

Genentech, Inc.

National Institutes of Health

Sage Science, Inc.

Jeffrey D Milbrandt

Paul T Kotzbauer

Eugene M Johnson

Patricia A Lampe

Yo Sasaki

Toshiyuki Araki

Robert D Klein

Aaron DiAntonio

Xianrong Mao

Fred DeSauvage

Kow Essuman

Rajesh Devraj

Robert Owen Hughes

Robert H Baloh

Raul Eduardo Krauss

Frederic J De Sauvage

T Christian Boles

Robi David Mitra

Ezra Solomon Abrams

Todd J Barbera

Tong Wu

Dan Summers

Adam Bloom

Bradley R Miller

Yurie Yamada

Craig A Press

Amy Strickland

Aaron Diantonio

Biplab Dasgupta

Jian Zhu

Among the various aspects of the present disclosure is the provision is the provision of a SARM1 activating agent or prodrug thereof and methods of using same.

Neurolytic agents and methods of using and identifying same

The present invention provides compounds useful as inhibitors of TIR NADase activity, compositions thereof, and methods of using the same. The present invention is useful for inhibition of TIR-domain NADase activity and/or treating microbial infection and/or modulating microbial physiology.

Identification of inhibitors of TcpC and TIR NADase activity

The present disclosure provides compounds useful as inhibitors of SARM1 NADase activity, compositions thereof, and methods of using the same. The present disclosure provides compounds useful for treating a neurodegenerative or neurological disease or disorder, compositions thereof, and methods of using the same.

Inhibitors of SARM1 NADase activity and uses thereof

A sample containing particles having high-molecular-weight (HMW) DNA is entrapped in a gel matrix, and the gel matrix is exposed to a lysis reagent configured to release the HMW DNA from the particles. The HMW DNA may be purified by subjecting the gel matrix to an electrophoretic field that removes the HMW DNA from the particles, lysis reagents, and/or other sample constituents, from the gel matrix such that the HMW DNA remains. The gel matrix may be subjected with DNA cleavase reagents configured to cleave at specific DNA sequences within the HMW DNA to liberate defined segments of the DNA as fragments of reduced size. The gel matrix may also be subjected to an electrophoretic field, which moves and separates the DNA fragments from uncleaved DNA of the HMW DNA, which remains substantially immobile. The electrophoretically separated DNA fragments may be isolated from the gel matrix.

Preparative electrophoretic method for targeted purification of genomic DNA fragments

Methods of treating or preventing axonal degradation in neuropathic diseases in mammals are disclosed. The methods can comprise administering to the mammal an effective amount of an agent that acts by increasing sirtuin activity in diseased and/or injured neurons. The methods can also comprise administering to the mammal an effective amount of an agent that acts by increasing NAD activity in diseased and/or injured neurons. Also disclosed are methods of screening agents for treating a neuropathies and recombinant vectors for treating or preventing neuropathies.

Methods and compositions for treating neuropathies

Methods of reducing Wallerian degeneration are disclosed. These methods comprise inhibiting expression or activity of a mixed lineage kinase such as a dual leucine-zipper-bearing kinase (DLK), inhibiting expression or activity of a molecule acting downstream from DLK, such as a c-Jun N-terminal kinase (JNK), or a combination thereof. Further disclosed are methods of screening candidate compounds for DLK inhibition activity. These methods comprise providing a neuronal culture comprising a plurality of axons; contacting the culture with a candidate compound and with an axon degeneration-triggering agent; and comparing axonal degeneration in the culture to a control culture comprising the axon degeneration-triggering agent but not the candidate compound.

Methods and compositions for inhibition of axonal degeneration by modulation of the DLK/JNK pathway

Methods are disclosed for decreasing stem cell proliferation, including cancer stem cell proliferation. These methods comprise administering to stem cells inhibitors of AMP activated protein kinase (AMPK). Methods for promoting stem cell growth by increasing stem cell proliferation, self-renewal and/or differentiation are also disclosed. These methods comprise administering AMPK activators to stem cells. Methods of achieving selective differentiation of stem cells are also disclosed. These methods comprise administering small molecules to stem cells that modulate AMPK activity. Applications of these methods are also disclosed, such as methods of increasing numbers of neuronal progenitor cells. These methods can be used therapeutically, such as for repair of spinal cord injuries, or for stimulating neurogenesis in the hippocampus, and other cell-based therapies. The methods can also be used for screening of compounds that can be activators or inhibitors of AMPK activity.

AMPK modulation as a method of regulating stem cell and cancer stem cell proliferation, self-renewal and differentiation

A novel growth factor, persephin, which belongs to the GDNF/neurturin family of growth factors, is disclosed. The human, mouse and rat amino acid sequences have been identified. Human, mouse and rat persephin genomic DNA sequences have been cloned and sequenced and the respective cDNA sequences identified. In addition, methods for treating degenerative conditions using persephin, methods for detecting persephin gene alterations and methods for detecting and monitoring patient levels of persephin are provided. Methods for identifying additional members of the persephin-neurturin-GDNF family of growth factors are also provided.

Persephin specific antibodies

A novel growth factor, neurturin, is disclosed and the human and mouse amino acid sequences are identified. Human and mouse neurturin genomic DNA sequences have been cloned and sequenced and the respective cDNA sequences identified. The subcloning into vectors and the preparation of cells stably transformed with the vectors are also disclosed. In addition, methods for treating degenerative conditions, tumor cells and obesity; methods for detecting gene alterations and methods for detecting and monitoring patient levels of neurturin are provided. Methods for identifying additional members of the neurturin-GDNF family of growth factors are also provided.

Neurturin antibody

Polynucleotides encoding human persephin and related growth factors

Chimeric GDNF family ligands which activate a GFR&#x3b1;/RET are disclosed. Included are chimeras which activate GFR&#x3b1;1/RET but do not activate GFR&#x3b1;2-RET or GFR&#x3b1;3-RET. The chimeras are useful in providing trophic support to a mammalian cell or in producing differentiation of a mammalian cell, or both, particularly when the cell is in a patient suffering from various diseases, in particular Parkinson's Disease.

GFR&#x3b1;1-RET specific agonists and methods therefor

A novel growth factor, neurturin, is disclosed. The human and mouse amino acid sequences have been identified. Human and mouse neurturin genomic DNA sequences have been cloned and sequences and the respective CDNA sequences identified. The subcloning into vectors and the preparation of cells stably transformed with the vectors is also disclosed. In addition, methods for treating degenerative conditions using neurturin, methods for detecting gene alterations and methods for detecting and monitoring patient levels of neurturin are provided. Methods for identifying additional members of the neurturin-GDNF family of growth factors are also provided.

Method of cell culture using neurturin

Growing community of inventors

St. Louis, MO, United States of America

Jeffrey D Milbrandt