Levamisole is ineffective in the treatment of amyotrophic lateral sclerosis

Olarte, Marcelo R.; Shafer, Stephen Q.

doi:10.1212/wnl.35.7.1063

Cited by 22 publications

(4 citation statements)

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“…Levamisole has strong immunomodulatory activity [27][28][29]. Early in its development large-scale clinical research programs tested the effect of levamisole in human diseases caused by impaired cellular immune mechanisms, including ALS where the drug was ineffective [11]. More promising results were obtained in a small trial of multiple sclerosis patients [30].…”

Section: Discussionmentioning

confidence: 99%

“…It is used outside the U.S. in humans and has been used as an adulterating agent in illicit street drugs [10]. Levamisole has been used in an ALS clinical trial in which the drug was administered once a week for 6 months; no benefit was observed [11]. Here, we have conducted a 14 week dosing study of these two drugs in the SOD1 G93A and Prp-TDP43 A315T models of ALS.…”

Section: Introductionmentioning

confidence: 99%

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Assessment of levamisole HCl and thymosin α1 in two mouse models of amyotrophic lateral sclerosis

Borchelt

Ellison

2023

Preprint

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Amyotrohpic 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 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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Assessment of levamisole HCl and thymosin α1 in two mouse models of amyotrophic lateral sclerosis

Borchelt

Ellison

2023

Preprint

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“…Many other clinical trials were conducted using immunomodulating agents [64,[79][80][81][82], agents modulating the cholinergic activity [83,84], antiviral agents [85,86], and gangliosides [87,88].…”

Section: Antioxidant Agentsmentioning

confidence: 99%

The Heterogeneity of Amyotrophic Lateral Sclerosis: A Possible Explanation of Treatment Failure

Beghi

Mennini

Bendotti

et al. 2007

CMC

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Amyotrophic lateral sclerosis (ALS) is a severe clinical condition characterized by upper and lower motor neuron degeneration for which there is no truly effective treatment. The absence of an effective treatment can be explained in part by the complex and heterogeneous genetic, biochemical, and clinical features of ALS. While ALS accounts for the majority of the motor neuron diseases, the recognition of disease variants and mimic syndromes may lead to further insights into possible causes for the generality of ALS. From a biochemical perspective, the process of motor neuron degeneration is complex and the multifactorial influences and potential biomarkers of ALS have never been assessed in the light of the clinical heterogeneity of ALS. Several genes and environmental influences have been suggested as possible risk factors of ALS. A better understanding of interactions between these risk factors, potential biomarkers and heterogeneous clinical features may lead to more clearly defined pathological profiles among individuals or groups of ALS patients and in turn lead to more focused therapeutic trials.

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“…Anti-inflammatory/ immunomodulatory Inosiplex [65], Tilorone [66], Gangliosides [67], Levamisole [68], Ciclosporin [69], IFN-a [70], Transfer factor [71], Cyclophosphamide [72], Thalidomide [73], IFN-ß-1a [74], Minocycline [75], Glatiramer acetate, ONO-2506PO Antioxidants/bioenergetics Acetylcysteine [76], Co-enzyme Q10 [77], Tamoxifen, Selegiline [78], Glutathione [79], Delta 9-Tetrahydrocannabinol Creatine monohydrate, Vitamin E, KNS-760704, MCI-186…”

Section: Introduction To the Compoundmentioning

confidence: 99%

Arimoclomol: a potential therapy under development for ALS

Lanka

Wieland

Barber

et al. 2009

Expert Opinion on Investigational Drugs

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Arimoclomol, an amplifier of heat shock protein expression involved in cellular stress response, has emerged as a potential therapeutic candidate in amyotrophic lateral sclerosis (ALS) in recent years. Treatment with arimoclomol was reported to improve survival and muscle function in a mouse model of motor neuron disease. Several single- and multiple-dose safety studies have been completed in healthy control subjects. A 3-month Phase IIa study in people with ALS demonstrated safety at dosages up to 300 mg/day and another study is currently recruiting participants with familial ALS caused by mutations in the superoxide dismutase gene. We review the rationale for testing arimoclomol in sporadic and familial ALS in the context of available safety and pharmacokinetic data. Published and unpublished literature relative to the drug in the past two decades is discussed. The current review attempts to bring together our existing understanding of the actions of arimoclomol with the disease profile of ALS. The pharmacological profile of arimoclomol and the available preclinical data make it a promising therapeutic possibility in ALS.

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Levamisole is ineffective in the treatment of amyotrophic lateral sclerosis

Cited by 22 publications

References 0 publications

Assessment of levamisole HCl and thymosin α1 in two mouse models of amyotrophic lateral sclerosis

Assessment of levamisole HCl and thymosin α1 in two mouse models of amyotrophic lateral sclerosis

The Heterogeneity of Amyotrophic Lateral Sclerosis: A Possible Explanation of Treatment Failure

Arimoclomol: a potential therapy under development for ALS

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