Lithium carbonate in amyotrophic lateral sclerosis

Chiò, Adriano; Borghero, Giuseppe; Calvo, Andrea; Capasso, Margherita; Caponnetto, Claudia; Corbo, Massimo; Giannini, Fabio; Logroscino, Giancarlo; Mandrioli, Jessica; Marcello, Norina; Mazzini, Letizia; Moglia, Cristina; Monsurrò, Maria Rosaria; Mora, Gabriele; Patti, Francesco; Perini, Michele; Pietrini, Vladimiro; Pisano, Fabrizio; Pupillo, Elisabetta; Sabatelli, Mario; Salvi, Fabrizio; Silani, Vincenzo; Simone, I. L.; Sorarù, Gianni; Tola, Maria Rosaria; Volanti, Paolo; Beghi, Ettore

doi:10.1212/wnl.0b013e3181ed9e7c

Cited by 94 publications

(61 citation statements)

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“…19,44 Recently, a Class II clinical trial provided evidence that therapeutic or subtherapeutic doses of lithium lack efficacy in clinical improvement for ALS patients. 20 Furthermore, concerns about the safety of lithium carbonate as a treatment for ALS patients have been raised after the halting of a trial that saw serious adverse effects in its participants.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

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Rapamycin treatment augments motor neuron degeneration in SOD1^G93Amouse model of amyotrophic lateral sclerosis

et al. 2011

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Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

“…[18][19][20] Since lithium is a multifunctional drug, it is very difficult to verify whether the therapeutic effects of lithium in ALS mice are directly related to autophagy. Thus, it is important to test more selective autophagy modulators in ALS.…”

Section: Introductionmentioning

confidence: 99%

Rapamycin treatment augments motor neuron degeneration in SOD1^G93Amouse model of amyotrophic lateral sclerosis

et al. 2011

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“…11,12 One enrolled 84 patients taking riluzole and was powered to detect the large positive effect reported in the initial trial. 2 It was stopped at the first interim analysis for futility against this endpoint.…”

Section: Figure 2 Als Functional Rating Scale-revised (Alsfrs-r) Slopmentioning

confidence: 99%

“…The other enrolled 171 patients who were randomly assigned to either a subtherapeutic or a higher therapeutic dose of lithium. 12 That study was stopped prematurely because of excessive dropouts and found no differences in efficacy measures between the groups or compared with control subjects from a disease registry. 12 Our findings provide additional information about longer treatment duration, safety concerns, and a trial design with historical controls.…”

Section: Figure 2 Als Functional Rating Scale-revised (Alsfrs-r) Slopmentioning

confidence: 99%

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Phase II screening trial of lithium carbonate in amyotrophic lateral sclerosis

Miller¹,

Moore²,

Forshew³

et al. 2011

Neurology

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Objective: To use a historical placebo control design to determine whether lithium carbonate slows progression of amyotrophic lateral sclerosis (ALS).Methods: A phase II trial was conducted at 10 sites in the Western ALS Study Group using similar dosages (300-450 mg/day), target blood levels (0.3-0.8 mEq/L), outcome measures, and trial duration (13 months) as the positive trial. However, taking riluzole was not a requirement for study entry. Placebo outcomes in patients matched for baseline features from a large database of recent clinical trials, showing stable rates of decline over the past 9 years, were used as historical controls. Results:The mean rate of decline of the ALS Functional Rating Scale-Revised was greater in 107 patients taking lithium carbonate (Ϫ1.20/month, 95% confidence interval [CI] Ϫ1.41 to Ϫ0.98) than that in 249 control patients (Ϫ1.01/month, 95% CI Ϫ1.11 to Ϫ0.92, p ϭ 0.04). There were no differences in secondary outcome measures (forced vital capacity, time to failure, and quality of life), but there were more adverse events in the treated group. Conclusions:The lack of therapeutic benefit and safety concerns, taken together with similar results from 2 other recent trials, weighs against the use of lithium carbonate in patients with ALS. The absence of drift over time and the availability of a large database of patients for selecting a matched historical control group suggest that use of historical controls may result in more efficient phase II trials for screening putative ALS therapeutic agents. Classification of evidence:This study provided Class IV evidence that lithium carbonate does not slow the rate of decline of function in patients with ALS over 13 months. Neurology ® 2011;77:973-979 GLOSSARY ALS ϭ amyotrophic lateral sclerosis; ALSFRS-R ϭ ALS Functional Rating Scale-Revised; CI ϭ confidence interval; FVC ϭ forced vital capacity; MINO ϭ minocycline in ALS trial; NSAE ϭ nonserious adverse event; QOL ϭ quality of life; SAE ϭ serious adverse event; WALS ϭ Western ALS Study Group.

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Advances in Translational Research in Neuromuscular Diseases

Pleasure¹

2011

Arch Neurol

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ew therapies developed over the past 3 years for previously intractable diseases of skeletal muscle, neuromuscular junctions, peripheral nerves, and motor neurons are now being incorporated into our standard neuromuscular clinical practice. The past 3 years were also marked by important advances in our understanding of the pathogenesis and pathophysiology of inherited and acquired neuromuscular diseases; these advances were acquired by the use of high-throughput nucleotide and protein analytic methods, novel animal models, and human-induced pluripotent stem cell-derived "diseases in a dish." Over the next decade, we can reasonably anticipate that these insights, coupled with advances in our ability to modulate immune mechanisms, to modify the activity of mutant genes, and to perform gene replacement therapies with enhanced viral vector-based and stem cell-based delivery systems, will revolutionize our management of neuromuscular diseases.

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Lithium carbonate in amyotrophic lateral sclerosis

Cited by 94 publications

References 23 publications

Rapamycin treatment augments motor neuron degeneration in SOD1^G93Amouse model of amyotrophic lateral sclerosis

Rapamycin treatment augments motor neuron degeneration in SOD1^G93Amouse model of amyotrophic lateral sclerosis

Phase II screening trial of lithium carbonate in amyotrophic lateral sclerosis

Advances in Translational Research in Neuromuscular Diseases

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Lithium carbonate in amyotrophic lateral sclerosis

Cited by 94 publications

References 23 publications

Rapamycin treatment augments motor neuron degeneration in SOD1G93Amouse model of amyotrophic lateral sclerosis

Rapamycin treatment augments motor neuron degeneration in SOD1G93Amouse model of amyotrophic lateral sclerosis

Phase II screening trial of lithium carbonate in amyotrophic lateral sclerosis

Advances in Translational Research in Neuromuscular Diseases

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Rapamycin treatment augments motor neuron degeneration in SOD1^G93Amouse model of amyotrophic lateral sclerosis

Rapamycin treatment augments motor neuron degeneration in SOD1^G93Amouse model of amyotrophic lateral sclerosis