ACTH (Acthar Gel) Reduces Toxic SOD1 Protein Linked to Amyotrophic Lateral Sclerosis in Transgenic Mice: A Novel Observation

Hasan Arrat; Thomas J Lukas; Teepu Siddique

doi:10.1371/journal.pone.0125638

ACTH (Acthar Gel) Reduces Toxic SOD1 Protein Linked to Amyotrophic Lateral Sclerosis in Transgenic Mice: A Novel Observation

PLoS One. 2015 May 8;10(5):e0125638. doi: 10.1371/journal.pone.0125638. eCollection 2015.

Authors

Hasan Arrat¹, Thomas J Lukas², Teepu Siddique¹

Affiliations

¹ Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611, United States of America.
² Department of Pharmacology, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611, United States of America.

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a complex etiology and pathology that makes the development of new therapies difficult. ACTH has neurotrophic and myotrophic effects, but has not been tested in an ALS mouse model. The G93A-SOD1 mouse model of ALS was used to test the ability of this drug to delay ALS-like symptoms. We showed that within a specific dose range, ACTH significantly postponed the disease onset and paralysis in the mouse model. To our surprise and of greater significance is that ACTH significantly reduced the levels of soluble SOD1 in the spinal cord and CNS tissues of G93A-SOD1 treated mice as well as cultured fibroblasts.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenocorticotropic Hormone / pharmacology
Adrenocorticotropic Hormone / therapeutic use*
Amyotrophic Lateral Sclerosis / metabolism
Amyotrophic Lateral Sclerosis / pathology
Amyotrophic Lateral Sclerosis / prevention & control*
Animals
Body Weight / drug effects
Cell Line
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Female
Fibroblasts / cytology
Fibroblasts / drug effects
Fibroblasts / metabolism
Humans
Male
Mice
Mice, Transgenic
Motor Activity / drug effects
Motor Neurons / metabolism
Mutation
Spinal Cord / metabolism
Superoxide Dismutase / analysis
Superoxide Dismutase / genetics
Superoxide Dismutase / metabolism*
Superoxide Dismutase-1
Survival Rate

Substances

SOD1 protein, human
Adrenocorticotropic Hormone
Sod1 protein, mouse
Superoxide Dismutase
Superoxide Dismutase-1

Grants and funding

The work was supported in part by Questcor Pharmaceuticals. Additional support was from the Les Turner ALS Foundation, the Les Turner Foundation/Herbert C. Wenske Professorship (to TS), Harold Post Research Professorship (to TS), Vena E. Schaff ALS Research Fund, the S.W. Ranson Fund in ALS Research, and the Foglia Family Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.