Riluzole and amyotrophic lateral sclerosis

Lacomblez, Lucette; Bensimon, Gilbert; Leigh, P. Nigel; Guillet, Philippe; Meininger, Vincent

doi:10.1016/s0140-6736(05)64506-0

Cited by 28 publications

(28 citation statements)

References 3 publications

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“…Percutaneous endoscopic gastrostomy tube insertion was more common among the riluzole cohort, which may account for some of the observed survival benefit. Furthermore, the higher frequency of early deaths among bulbar-onset patients (53 % of the 137 bulbar patients died in the first 12 months compared with 30 % among the limb-onset patients) may falsely magnify the beneficial effect of riluzole [13]. If the bulbar effect is genuine, one possible explanation may be that riluzole exerts a selective, beneficial effect on brainstem motor neurons, though there are no in vitro data to support this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

An outcome study of riluzole in amyotrophic lateral sclerosis

Traynor

Alexander

Corr

et al. 2003

Journal of Neurology

139

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Riluzole is the only therapy proven in clinical trials to prolong amyotrophic lateral sclerosis (ALS) survival (approximately three months). Questions remain concerning riluzole's effectiveness in everyday practice, the appropriate duration of treatment, which certain subtypes of ALS specifically benefit from the medication, and whether early administration prolongs survival in ALS patients. We report the results of a population-based outcome study of riluzole in the Irish ALS population over a five-year period. Using data from the Irish ALS Register, we examined the survival of patients diagnosed with ALS between 1 January 1996 and 31 December 2000 who attended a general neurology clinic (n = 264 patients, MD = 16). An intention to treat analysis is employed. 149 (61 %) patients were prescribed riluzole and the remaining 99 (39 %) were not. Riluzole therapy reduced mortality rate by 23 % and 15 % at 6 and 12 months respectively and prolonged survival by approximately four months. This beneficial effect was lost in prolonged follow-up. Suspected or possible ALS patients receiving riluzole experienced similar improvement in survival as the overall cohort. Survival benefit was more marked among patients with bulbar-onset disease. Multivariate analysis did not show riluzole to be an independent predictor of survival. We conclude that riluzole therapy improves ALS survival in everyday clinical practice by a short period of time. This beneficial effect is transient and stopping the medication in advanced ALS should be reconsidered. Bulbar-onset patients appear to particularly benefit from riluzole for unclear reasons. Our initial observations support riluzole use in early ALS.

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Section: Discussionmentioning

confidence: 99%

An outcome study of riluzole in amyotrophic lateral sclerosis

Traynor

Alexander

Corr

et al. 2003

Journal of Neurology

139

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“…For example, a recent screen of 184,880 novel compounds using a "filter retardation assay" of Huntington's disease (HD) aggregates led to the identification of multiple lead compounds, including a number of benzothiazoles that inhibited polyglutamine-mediated aggregation of toxic and misfolded proteins (Heiser et al, 2002). Because riluzole, a closely related benzothiazole, had previously shown therapeutic benefit in patients with amyotrophic lateral sclerosis (Lacomblez et al, 1996), drugs from this structural class of molecules were tested for further development. In a cell culture model of aggregation, all primary hits were found to be toxic to cells, and in an animal model of HD, none of the compounds was of therapeutic value (Hockly et al, 2006).…”

Section: A Traditional Drug Discoverymentioning

confidence: 99%

Human Disease Models inDrosophila melanogasterand the Role of the Fly in Therapeutic Drug Discovery

2011

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“…Lou Gehrig's disease (ALS), is a devastating neurodegenerative disease, characterized by the progressive loss of motor neurons in ventral spinal cord and motor cortex. Studies of sporadic ALS have suggested that an excitotoxic mechanism promotes the development and progression of this disease, as ALS patients demonstrate elevated levels of glutamate in the spinal cord and cerebrospinal fluid and decreased glutamate transporter activity (Rothstein et al 1990;Rothstein et al 1992;Bensimon et al 1994;Rothstein et al 1995;Lacomblez et al 1996). We examined the effect of PG receptors on postnatal motor neuron survival in vitro in which chronic glutamate toxicity is induced by treatment of organotypic spinal cord cultures with glutamate transporter inhibitors, resulting in motor neuron loss after several weeks of treatment (Rothstein et al 1993).…”

Section: Paradoxical Neuroprotection Elicited By Specific Prostaglandmentioning

confidence: 99%

Function of COX-2 and Prostaglandins in Neurological Disease

et al. 2007

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Induction of COX-2 expression and enzymatic activity promotes neuronal injury in a number of models of neurological disease. Inhibition of COX-2 activity, either genetically or pharmacologically, has been shown to be neuroprotective in rodent models of stroke, Parkinson's disease, and amyotrophic lateral sclerosis. Inhibition of COX activity with nonsteroidal anti-inflammatory drugs (NSAIDs) reduces inflammation and amyloid accumulation in murine transgenic models of Familial Alzheimer's disease, and the use of NSAIDs decreases the risk of developing Alzheimer's disease in healthy aging populations. COX-mediated neuronal injury is presumed be due to downstream effects of one or more prostaglandin products including PGE2, PGD2, PGF2alpha, PGI2 (prostacylin) and TXA2 (thromboxane) that effect cellular changes through activation of specific prostaglandin receptor subtypes and second messenger systems. In this proceeding, we review recent data demonstrating effects of prostaglandin signaling on neuronal viability that are paradoxically protective, when taken in the context that COX-2 induces neuronal injury in the setting of excitotoxicity. Conversely, in the context of an inflammatory stimulus, the EP2 receptor enhances neuronal injury. These findings argue for an additional level of complexity in the prostaglandin response in neurological disease.

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Riluzole and amyotrophic lateral sclerosis

Cited by 28 publications

References 3 publications

An outcome study of riluzole in amyotrophic lateral sclerosis

An outcome study of riluzole in amyotrophic lateral sclerosis

Human Disease Models inDrosophila melanogasterand the Role of the Fly in Therapeutic Drug Discovery

Function of COX-2 and Prostaglandins in Neurological Disease

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