A controlled clinical trial of baclofen as protective therapy in early huntington's disease

Shoulson, Ira; Odoroff, Charles L.; Oakes, David; Behr, Jill; Goldblatt, David; Caine, Eric D.; Kennedy, Judith; Miller, C.D.; Bamford, Kathryn A.; Rubin, Allen; Plumb, Sandra; Kurlan, Roger

doi:10.1002/ana.410250308

Cited by 102 publications

(49 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although some can reduce dystonia, at least in animal models (Hamann and Richter, 2002), for the most part clinical trials have been unsuccessful (Shoulson et al, 1978;Waddington and Cross, 1984). Specifically, in spite of early reports of limited success in retarding disease progression using baclofen, a GABA B receptor agonist, controlled trials have been unsuccessful, casting doubt on the efficacy of reducing presynaptic release of glutamate (Shoulson et al, 1989). This is not unexpected in view of our findings showing increased GABAergic tone and reduced glutamate synaptic activity in mouse models.…”

Section: Drugs That Reduce Cortical Excitability and Glutamate Releasementioning

confidence: 64%

The corticostriatal pathway in Huntington's disease

Cepeda

André

et al. 2007

Progress in Neurobiology

286

265

View full text Add to dashboard Cite

The corticostriatal pathway provides most of the excitatory glutamatergic input into the striatum and it plays an important role in the development of the phenotype of Huntington's disease (HD). This review summarizes results obtained from genetic HD mouse models concerning various alterations in this pathway. Evidence indicates that dysfunctions of striatal circuits and cortical neurons that make up the corticostriatal pathway occur during the development of the HD phenotype, well before there is significant neuronal cell loss. Morphological changes in the striatum are probably primed initially by alterations in the intrinsic functional properties of striatal medium-sized spiny neurons. Some of these alterations, including increased sensitivity of N-methyl-D-aspartate receptors in subpopulations of neurons, might be constitutively present but ultimately require abnormalities in the corticostriatal inputs for the phenotype to be expressed. Dysfunctions of the corticostriatal pathway are complex and there are multiple changes as demonstrated by significant age-related transient and more chronic interactions with the disease state. There also is growing evidence for changes in cortical microcircuits that interact to induce dysfunctions of the corticostriatal pathway. The conclusions of this review emphasize, first, the general role of neuronal circuits in the expression of the HD phenotype and, second, that both cortical and striatal circuits must be included in attempts to establish a framework for more rational therapeutic strategies in HD. Finally, as changes in cortical and striatal circuitry are complex and in some cases biphasic, therapeutic interventions should be regionally specific and take into account the temporal progression of the phenotype.

show abstract

Section: Drugs That Reduce Cortical Excitability and Glutamate Releasementioning

confidence: 64%

The corticostriatal pathway in Huntington's disease

Cepeda

André

et al. 2007

Progress in Neurobiology

286

265

View full text Add to dashboard Cite

show abstract

“…Baclofen was studied in a RCT involving 60 patients by Shoulson et al [36], showing no benefit over placebo.…”

Section: Gaba Agonistsmentioning

confidence: 99%

The Pathophysiology and Pharmacological Treatment of Huntington Disease

Pidgeon

Rickards

2013

Behavioural Neurology

View full text Add to dashboard Cite

Abstract.Introduction: Huntington disease (HD) is a progressive neurodegenerative condition characterised by motor, cognitive and behavioural dysfunction, and has an autosomal dominant mode of inheritance. As there is currently no treatment to delay progression of the disease, pharmacological intervention is aimed at symptomatic relief. Methods: We set out to assess the current evidence on the pharmacological treatment of motor and non-motor symptoms in HD by carrying out a systematic literature review across five large scientific databases. Results: The search generated 23 original studies meeting our search criteria. Studies on the following drug classes were obtained: dopamine (DA) depleting agents, neuroleptics, anti-glutamatergic agents, acetylcholinesterase inhibitors, GABA agonists, cannabinoids, antidepressants and potential neuroprotective agents. Tetrabenazine (TBZ), a DA depleting agent, was the only pharmacotherapy shown to have a clinically meaningful, statistically significant effect on chorea. The majority of the reviewed studies focussed on the treatment of motor symptoms of HD. Discussion: Overall, the evidence base for the pharmacological management of HD is poor. There is a clear need for future high quality randomised controlled trials on the symptomatic treatment of HD, particularly on the pharmacotherapy of non-motor symptoms of HD.

show abstract

“…Otros inhibidores o bloqueantes del glutamato. El baclofen, agonista GABAérgico capaz de retrasar e inhibir la liberación de glutamato y aspartato principalmente a nivel de la vía corticoestriatal, fue empleado en EH durante 30 meses a razón de 60mg/día evidenciando un discreto empeoramiento de los síntomas 13 .…”

Section: Terapias Farmacológicas Expe-rimentalesunclassified

Enfermedad de Huntington: tratamiento

Gatto¹

2013

Rev Neuropsiquiatr

View full text Add to dashboard Cite

show abstract

A controlled clinical trial of baclofen as protective therapy in early huntington's disease

Cited by 102 publications

References 30 publications

The corticostriatal pathway in Huntington's disease

The corticostriatal pathway in Huntington's disease

The Pathophysiology and Pharmacological Treatment of Huntington Disease

Enfermedad de Huntington: tratamiento

Contact Info

Product

Resources

About