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Assessment of Levamisole HCl and Thymosin α1 in Two Mouse Models of Amyotrophic Lateral Sclerosis

Author(s): David R. Borchelt, Siobhan Ellison

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes generalized muscle weakness and atrophy. Neuropathologically, ALS is defined by severe loss of upper and lower motor neurons with a robust neuroinflammatory response. In the present study, we have examined the potential utility of two drugs that have indications as immune modulators, levamisole HCl and thymosin α1. These drugs were tested in two models that reproduce aspects of ALS. We conducted a 14-week dosing study of these two drugs in the SOD1G93A and Prp-TDP43A315T models of ALS. The drugs were given once daily for two weeks and then every other day for 6 weeks for a total of 8 weeks of treatment. Outcome measurements included efficacy assessment on the neuromuscular phenotypes, and pathological analyses of ubiquitin load and neuro-inflammatory markers in spinal motor neurons. Neither of these drug treatments produced significant extensions in survival; however, there were changes in ubiquitin load in SOD1G93A mice that suggest the drugs could be beneficial as additions to other therapies.

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