Jeffrey Milbrandt - Clayton MO, US Biplab Dasgupta - St. Louis MO, US
Assignee:
Washington University - Saint Louis MO
International Classification:
G01N 33/53 G01N 33/68
US Classification:
435 71
Abstract:
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.
Methods And Compositions For Treating Neuropathies
Jeffrey Milbrandt - Clayton MO, US Biplab Dasgupta - St. Louis MO, US
Assignee:
WASHINGTON UNIVERSITY - St. Louis MO
International Classification:
A61K 49/00 A61K 31/05 C12Q 1/02 A61P 25/00
US Classification:
424 92, 514736, 435 29
Abstract:
Methods of treating or preventing axonal degradation in neuropathic diseases and neurological disorders in mammals are disclosed. The methods can comprise administering to the mammal an effective amount of an agent that acts at least in part by increasing sirtuinAMPK activity, LKB 1 activity and/or CaMKKβ 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, alone or in combination with agents that act by other mechanisms. Also disclosed are methods of screening agents for treating a neuropathies and recombinant vectors for treating or preventing such neuropathies.
Methods And Compositions For Inhibition Of Axonal Degeneration By Modulation Of The Dlk/Jnk Pathway
Aaron DiAntonio - Olivette MO, US Bradley R. Miller - St. Louis MO, US Jeffrey D. Milbrandt - Clayton MO, US Craig A. Press - St. Louis MO, US
Assignee:
WASHINGTON UNIVERSITY - St. Louis MO
International Classification:
A61K 31/7088 A61K 31/415 C12Q 1/48
US Classification:
514 44 A, 514406, 435 15
Abstract:
Methods of reducing Wallerian degeneration are disclosed. These methods comprise inhibiting expression or activity of a mixed lineage kinas 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
WASHINGTON UNIVERSITY - Saint Louis MO, US Bradley Miller - Saint Louis MO, US Jeffrey Milbrandt - Saint Louis MO, US Craig Press - Saint Louis MO, US
Assignee:
WASHINGTON UNIVERSITY - Saint Louis MO
International Classification:
A61K 31/713
US Classification:
514 44 A
Abstract:
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 Treating Neuropathies
Jeffrey Milbrandt - Clayton MO, US Biplab Dasgupta - St. Louis MO, US
Assignee:
WASHINGTON UNIVERSITY - St. Louis MO
International Classification:
G01N 33/50 A61K 31/05
US Classification:
514734, 435 29
Abstract:
Methods of treating or preventing axonal degradation in neuropathic diseases and neurological disorders in mammals are disclosed. The methods can comprise administering to the mammal an effective amount of an agent that acts at least in part by increasing sirtuin AMPK activity, LKB activity and/or CaMKKβ 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, alone or in combination with agents that act by other mechanisms. Also disclosed are methods of screening agents for treating a neuropathies and recombinant vectors for treating or preventing such neuropathies.
Medicine Doctors
Dr. Jeffrey Milbrandt, Saint Louis MO - MD (Doctor of Medicine)
Washington University In St. Louis
Chairman Department of Genetics
Washington University In St. Louis
Professor
University of Virginia Jul 1, 1978 - Sep 1, 1983
Resident In Pathology
Education:
University of Virginia School of Medicine 1980 - 1983
Doctorates, Doctor of Philosophy, Biochemistry
Washington University School of Medicine In St. Louis 1974 - 1978
Doctor of Medicine, Doctorates, Medicine
University of Nebraska - Lincoln 1971 - 1974
Bachelors
Loganview High School 1967 - 1971
University of Virginia School of Medicine