Als Therapy Development Foundation, Inc.

Pathologica LLC

Alsgen, Inc.

Sean Scott

Tennore M Ramesh

Michael S McGrath

Laurence J Marton

Daniel Benjamin

Methods for modulating proteasome activity in a subject is provided. Proteasome activity is modulated by administering a therapeutically effective amount of proteasome modulating pharmacological agent to a subject. In a preferred embodiment, the proteasome modulating pharmacological agent is a protease inhibitor. In another aspect, a screening assay for detecting and identifying proteasome modulating pharmacological agents to modulate proteasome activity in a subject is also provided.

Treatment of neurodegenerative diseases using proteasome modulators

The present invention provides methods and compositions for modulating polyamine pathway activity as a means for ameliorating neurodegenarative disorders. In particular, for ameliorating the symptoms or onset of amyotrophic lateral sclerosis (ALS) by modulating the gene and protein products involved the polyamine pathway, such as by inhibiting the enzyme, ornithine decarboxylase (ODC), involved in the synthesis of the polyamine, putrescine. Compositions and methods are disclosed for inhibiting the polyamine pathway producing lower polyamine levels resulting in a beneficial effect on ALS. This can be accomplished by using modulating agents such as analogs, or polyamine analogs, and antiproliferative drugs. In particular, the ODC inhibitor difuoromethylornithine (DFMO) is disclosed as a useful pharmacological agent in the modulation and treatment of ALS. Screening assays for pharmacological agents that are capable of decreasing polyamine levels and/or reducing cell proliferation are also disclosed.

Use of difluoromethylornithine (DFMO) for the treatment of amyotrophic lateral sclerosis

The present invention provides methods and compositions for modulating polyamine pathway activity as a means for ameliorating neurodegenarative disorders. In particular, for ameliorating the symptoms or onset of amyotrophic lateral sclerosis (ALS) by modulating the gene and protein products involved the polyamine pathway, such as by inhibiting the enzyme, ornithine decarboxylase (ODC), involved in the synthesis of the polyamine, putrescine. Compositions and methods are disclosed for inhibiting the polyamine pathway producing lower polyamine levels resulting in a beneficial effect on ALS. This can be accomplished by using modulating agents such as analogs, or polyamine analogs, and antiproliferative drugs. Screening assays for pharmacological agents that are capable of decreasing polyamine levels and/or reducing cell proliferation are also disclosed.

Treatment of neurodegenerative disorders through the modulation of the polyamine pathway

The invention provides methods of monitoring amyotrophic lateral sclerosis (ALS) disease development or progression and monitoring an ALS therapy by determining the level of HLA-DR expression by CD14+ monocytes and/or the percentage of CD16+ cells in the population of CD14+ cells and/or the number of CD14+/CD16+ cells in peripheral blood of an individual with ALS. The invention is also directed to methods for decreasing the number of circulating CD14+ monocytes and/or the population of CD14+/CD16+ cells and/or the number of CD14+/CD16+ cells in an individual with ALS. The invention is also directed to methods of screening for agents which decrease the population of CD14+ monocytes with elevated HLA-DR expression and/or the population of CD14+/CD16+ cells and/or the number of CD14+/CD16+ cells in an individual with ALS.

Screening for agents effective in decreasing abnormal macrophages associated with amyotrophic lateral sclerosis

The present invention provides methods and compositions for modulating polyamine pathway activity as a means for ameliorating neurodegenarative disorders. In particular, for ameliorating the symptoms or onset of amyotrophic lateral sclerosis (ALS) by modulating the gene and protein products involved the polyamine pathway, such as by inhibiting the enzyme, ornithine decarboxylase (ODC), involved in the synthesis of the polyamine, putrescine. Compositions and methods are disclosed for inhibiting the polyamine pathway producing lower polyamine levels resulting in a beneficial effect on ALS. This can be accomplished by using modulating agents such as analogs, or polyamine analogs, and antiproliferative drugs. In particular, the polyamine analog N(1),N(11)-diethylnorspermine (DENSPM) is disclosed as a useful modulating agent in the treatment of ALS. Screening assays for pharmacological agents that are capable of decreasing polyamine levels and/or reducing cell proliferation are also disclosed.

Growing community of inventors

San Francisco, CA, United States of America

Sean Scott