Johns Hopkins University

Temple University

Institute of Organic Chemistry & Biochemistry

Norman J Haughey

Barbara S Slusher

Camilo Rojas

Joseph P Steiner

Avindra Nath

Ajit G Thomas

Robert J Cotter

Kamel Khalili

Xin Hu

Marc Ferrer

Salim Merali

Jay F Rappaport

Michal Sala

Radim Nencka

Ned Sacktor

Hubert Hrebabecky

Caroline F Anderson

David Irani

Carlos A Barrerro

Methods for treating one or more diseases associated with neutral sphingomyelinase 2 (nSMase2) in a subject in need of treatment thereof, the method comprising administering to the subject a therapeutically effective amount of 2,6-dimethoxy-4-(5-phenyl-4-thiophen-2-yl-1H-imidazol-2-yl)-phenol (DPTIP) or a pharmaceutically acceptable salt thereof, are disclosed.

2,6-dimethoxy-4-(5-phenyl-4-thiophene-2-yl-1H-imidazol-2-yl)-phenol (DPTIP) a small molecule inhibitor of neutral sphingomyelinase 2 (nSMase-2) for the treatment of neurodegenerative and oncologic diseases

Methods for treating a Human Immunodeficiency Virus (HIV) infection comprising administering to a subject in need of treatment thereof an effective amount of a small molecule nSMase2 inhibitor.

Inhibition of nSMase for the treatment of human immunodeficiency virus infection

Small molecule inhibitors of neutral sphingomyelinase 2 (nSMase2) and their use for treating neurodegenerative diseases, such as, neurodegenerative diseases associated with high levels of ceramide, including, but not limited to Alzheimer's disease (AD), HIV-associated neurocognitive disorder (HAND), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), and, in other aspects, for treating cancer, are provided.

Small molecule inhibitors of neutral sphingomyelinase 2 (nSMase2) for the treatment of neurodegenerative diseases

Provided is a method of detecting mild neurocognitive disturbance (MNCD) or HIV associated dementia (HAD) in a patient comprising detecting the level of acetyl spermine and/or acetyl spermidine from a cerebrospinal fluid test sample of the patient; and comparing the level of acetyl spermine and/or acetyl spermidine in the test sample to the level of the acetyl spermine and/or acetyl spermidine in a cerebrospinal fluid control sample or to a control value for lack of neurocognitive impairment, MNCD or HAD; wherein an elevated level of acetyl spermine and/or acetyl spermidine in the test sample as compared to the level in the control sample or a control value for lack of neurocognitive impairment, or a level of acetyl spermine and/or acetyl spermidine that is similar to that of a control value for MNCD or HAD, indicates that the patient suffers from MNCD or HAD. Also provided are methods for measuring the progression of an HIV-1-associated neurocognitive disorder, as well as methods for staging such a disorder.

Detection of HIV-1-associated neurocognitive disorders

Disclosed herein are neuroprotective compounds. Methods for the preparation of such compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the compounds disclosed, alone or in combination with other therapeutic agents, for the treatment of neurodegenerative conditions are provided.

Role of limonoid compounds as neuroprotective agents

Biological markers for multiple sclerosis, and their use in the diagnosis and prognosis of the disease, are described. Also described are methods for treating multiple sclerosis by administering an inhibitor of cathepsin B activity or a neuroprotective composition comprising a modified terpenoid compound. Also described are isolated polypeptide biomarkers, polynucleotides encoding the polypeptide biomarkers, and antibodies that bind specifically to the polypeptide biomarkers. Further described are kits that include the above-mentioned isolated polypeptide biomarkers, the polynucleotides encoding them, or specific antibodies against the polypeptide biomarkers.

Methods for diagnosis and optimizing treatment of multiple sclerosis

Growing community of inventors

Baltimore, MD, United States of America

Norman J Haughey