Lithium treatment of Huntington's chorea

Vestergaard, Per; Baastrup, P. C.; Petersson, Harry

doi:10.1111/j.1600-0447.1977.tb03561.x

Cited by 29 publications

(3 citation statements)

References 11 publications

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“…Combined therapy with lithium and neuroleptics also proved beneficial in several HD patients (Anden et al, 1973; Leonard et al, 1974; 1975; Manyam & Bravo-Fernandez, 1973; Schenk & Leijnse-Ybema, 1974). However, some other reports showed that lithium exerted no beneficial effects in HD patients (Aminoff & Marshall, 1974; Vestergaard et al, 1977). In some instances, lithium treatment even worsened motor and cognitive performance, particularly when used as the sole therapeutic agent (Carman et al, 1974; Leonard et al, 1974).…”

Section: Lithium In Models Of Cns Disorders and Its Clinical Implimentioning

confidence: 92%

Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders

Chiu

Chuang

2010

Pharmacology & Therapeutics

199

198

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Lithium has been used clinically to treat bipolar disorder for over half a century, and remains a fundamental pharmacological therapy for patients with this illness. Although lithium’s therapeutic mechanisms are not fully understood, substantial in vitro and in vivo evidence suggests that it has neuroprotective/neurotrophic properties against various insults, and considerable clinical potential for the treatment of several neurodegenerative conditions. Evidence from pharmacological and gene manipulation studies support the notion that glycogen synthase kinase-3 inhibition and induction of brain-derived neurotrophic factor-mediated signaling are lithium’s main mechanisms of action, leading to enhanced cell survival pathways and alteration of a wide variety of downstream effectors. By inhibiting N-methyl-D-aspartate receptor-mediated calcium influx, lithium also contributes to calcium homeostasis and suppresses calcium-dependent activation of pro-apoptotic signaling pathways. In addition, lithium decreases inositol 1,4,5-trisphosphate by inhibiting phosphoinositol phosphatases, a process recently identified as a novel mechanism for inducing autophagy. Through these mechanisms, therapeutic doses of lithium have been demonstrated to defend neuronal cells against diverse forms of death insults and to improve behavioral as well as cognitive deficits in various animal models of neurodegenerative diseases, including stroke, amyotrophic lateral sclerosis, fragile X syndrome, as well as Huntington’s, Alzheimer’s, and Parkinson’s diseases, among others. Several clinical trials are also underway to assess the therapeutic effects of lithium for treating these disorders. This article reviews the most recent findings regarding the potential targets involved in lithium’s neuroprotective effects, and the implication of these findings for the treatment of a variety of diseases.

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Section: Lithium In Models Of Cns Disorders and Its Clinical Implimentioning

confidence: 92%

Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders

Chiu

Chuang

2010

Pharmacology & Therapeutics

199

198

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“…These trials included only small numbers of patients (9, 6, and 6) for very short time periods (6–12 weeks). In each case, the findings indicated that there were no improvements in involuntary movements, hyperkinesia, motor skills, or in the ability to perform everyday tasks, leading to the conclusion that lithium did not appear to be of therapeutic value in HD (Aminoff and Marshall, 1974 ; Leonard et al, 1975 ; Vestergaard et al, 1977 ). Since the 1970s, there have not been any reported human clinical trials utilizing lithium for treatment of HD; however, there has been a recent off-label use of lithium in a case study involving three individuals.…”

Section: Lithium Effects In Other Neurodegenerative Diseasesmentioning

confidence: 99%

Potential application of lithium in Parkinson's and other neurodegenerative diseases

Lazzara

Kim

2015

Front. Neurosci.

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Lithium, the long-standing hallmark treatment for bipolar disorder, has recently been identified as a potential neuroprotective agent in neurodegeneration. Here we focus on introducing numerous in vitro and in vivo studies that have shown lithium treatment to be efficacious in reducing oxidative stress and inflammation, increasing autophagy, inhibiting apoptosis, and decreasing the accumulation of α-synulcein, with an emphasis on Parkinson's disease. A number of biological pathways have been shown to be involved in causing these neuroprotective effects. The inhibition of GSK-3β has been the mechanism most studied; however, other modes of action include the regulation of apoptotic proteins and glutamate excitotoxicity as well as down-regulation of calpain. This review provides a framework of the neuroprotective effects of lithium in neurodegenerative diseases and the putative mechanisms by which lithium provides the protection. Lithium-only treatment may not be a suitable therapeutic option for neurodegenerative diseases due to inconsistent efficacy and potential side-effects, however, the use of low dose lithium in combination with other potential or existing therapeutic compounds may be a promising approach to reduce symptoms and disease progression in neurodegenerative diseases.

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“…Taken together, these clinical studies support lithium's potential to improve the psychiatric and possibly motor symptoms of HD. Despite these findings, two placebo-controlled, blind clinical trials reported that lithium was ineffective in the treatment of choreiform movements 156 , 158 . However, in both studies, sample size was small, the duration of lithium treatment was relatively short, and standardized measures were not used to report mood changes.…”

Section: Clinical Trials Of Lithium and Vpa In Hdmentioning

confidence: 99%

Preclinical and Clinical Investigations of Mood Stabilizers for Huntington's Disease: What Have We Learned?

Scheuing¹,

Chiu²,

Liao³

et al. 2014

Int. J. Biol. Sci.

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Huntington's disease (HD) is a lethal, autosomal dominant neurodegenerative disorder caused by CAG repeat expansions at exon 1 of the huntingtin (Htt) gene, which encodes for a mutant huntingtin protein (mHtt). Prominent symptoms of HD include motor dysfunction, characterized by chorea; psychiatric disturbances such as mood and personality changes; and cognitive decline that may lead to dementia. Pathologically multiple complex processes and pathways are involved in the development of HD, including selective loss of neurons in the striatum and cortex, dysregulation of cellular autophagy, mitochondrial dysfunction, decreased neurotrophic and growth factor levels, and aberrant regulation of gene expression and epigenetic patterns. No cure for HD presently exists, nor are there drugs that can halt the progression of this devastating disease. Therefore, the need to discover neuroprotective modalities to combat HD is critical. In basic and preclinical studies using cellular and animal HD models, the mood stabilizers lithium and valproic acid (VPA) have shown multiple beneficial effects, including behavioral and motor improvement, enhanced neuroprotection, and lifespan extension. Recent studies in transgenic HD mice support the notion that combined lithium/VPA treatment is more effective than treatment with either drug alone. In humans, several clinical studies of HD patients found that lithium treatment improved mood, and that VPA treatment both stabilized mood and moderately reduced chorea. In contrast, other studies observed that the hallmark features of HD were unaffected by treatment with either lithium or VPA. The current review discusses preclinical and clinical investigations of the beneficial effects of lithium and VPA on HD pathophysiology.

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Lithium treatment of Huntington's chorea

Cited by 29 publications

References 11 publications

Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders

Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders

Potential application of lithium in Parkinson's and other neurodegenerative diseases

Preclinical and Clinical Investigations of Mood Stabilizers for Huntington's Disease: What Have We Learned?

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