Emory University

Donald G Stein

Iqbal Sayeed

Dennis C Liotta

Michael G Natchus

David Brian Guthrie

Mark Andrew Lockwood

David W Wright

Mark A Lockwood

Arthur L Kellermann

Stuart W Hoffman

Douglas W Lowery-North

Christopher MacNevin

Fahim Atif

Sarah Cutler

Christopher Macnevin

David B Guthrie

Sarah Melissa Cutler

Arthur L Kellerman

This disclosure relates to progesterone derivatives and uses related thereto. In certain embodiments, the disclosure relates to compounds disclosed herein and uses for managing inflammation resulting from traumatic brain injury or stroke.

Progesterone analogs and uses related thereto

This disclosure relates to progesterone phosphate derivatives and uses related thereto. In certain embodiments, the disclosure relates to compounds disclosed herein and uses for managing inflammation such as those resulting from traumatic brain injury or stroke.

Progesterone phosphate analogs and uses related thereto

This disclosure relates to progesterone phophate derivatives and uses related thereto. In certain embodiments, the disclosure relates to compounds disclosed herein and uses for managing inflammation such as those resulting from traumatic brain injury or stroke.

Provided are steroid analogues functionalized with polar substituents at the C3 and/or C20 positions of the steroid ring system that exhibit improved water solubility. Also provided are pharmaceutical compositions comprising the steroid analogues and methods using the novel steroid analogues for the treatment and prevention of neurodegeneration in a patient following injury to the central nervous system.

Steroid analogues for neuroprotection

Use of compounds disclosed herein, typically progesterone or analog or derivative thereof, in the treatment of central nervous system cancers, specifically neuroblastoma and glioblastoma is provided. The treatment offers a reduced toxicity as compared to the currently available chemotherapeutic agents. The progesterone may be administered alone or in combination with, or in conjunction with other therapeutic agents.

Method for the treatment of central nervous system cancers and compositions related thereto

The present invention provides methods for the treatment or the prevention of neuronal damage in the CNS. Specifically, the methods of the invention provide for the administration of a therapeutically effective amount of a progestin or progestin metabolite following a traumatic or ischemic injury to the CNS such that, prior to termination of administration of the progestin or progestin metabolite the administration is tapered to avoid withdrawal. The drug taper employed can involve a linear taper, an exponential taper, progressively dividing administered doses by 50%, or can be determined based on the treating physician's assessment of the patient's response to therapy. The tapered administration methods of the present invention may be used in combination with any therapeutic protocol or regimen for the administration of a therapeutically effective amount of a progestin or progestin metabolite to treat a traumatic or ischemic CNS injury.

Methods for the treatment of a central nervous system injury via a tapered administration protocol

Methods of treating a subject with a traumatic central nervous system injury, more particularly, a traumatic brain injury, are provided. The methods comprise a therapy comprising a constant or a two-level dosing regime of progesterone. In one method, a subject in need thereof is administered at least one cycle of therapy, wherein the cycle of therapy comprises administering a therapeutically effective two-level intravenous dosing regime of progesterone. The two-level dosing regime comprises a first time period, wherein a higher hourly dose of progesterone is administered to the subject, followed by a second time period, wherein a lower hourly dose of progesterone is administered to the subject.

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Atlanta, GA, United States of America

Donald G Stein