The Riluzole Early Access Programme: descriptive analysis of 844 patients in France

Meininger, Vincent; Dib, Michel; Aubin, F.; Jourdain, Gonzague; Zeisser, Philippe

doi:10.1007/bf03160577

Cited by 20 publications

(14 citation statements)

References 8 publications

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“…8,20,26 A recent well-designed study by Armon et al 3 demonstrated the relationship between rate of estimated linear disease progression and survival. When their patients were divided into groups with faster or slower progression, a significant difference in survival was observed.…”

Section: Discussionmentioning

confidence: 98%

Disease progression in amyotrophic lateral sclerosis: Predictors of survival

et al. 2002

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Predicting the rate of disease progression has become important as trials of new medical treatments for amyotrophic lateral sclerosis (ALS) are planned. Bulbar onset, early impairment of forced vital capacity, and older age have all been associated with shorter survival. We performed a retrospective study to compare survival factors with disease progression in a German ALS population. We analyzed disease progression in 155 patients at intervals of 4 months over a period of 3 years. To evaluate disease progression, the ALS functional rating scale (ALS-FRS), forced vital capacity (FVC%), and a Medical Research Council (MRC) compound score based on a nine-step modified MRC scale were used. We compared age (< 55 years vs. > or =55 years), different sites of disease onset (bulbar vs. limb), and gender to the rate of disease progression and performed survival analyses. No overall significant difference could be detected when analyzing these subgroups with regard to disease progression. By contrast, significantly longer survival was observed in the younger age group (56 months vs. 38 months, P < 0.0001) and in patients with limb-onset disease (51 months vs. 37 months, P = 0.0002). Using Cox analyses values we found that the declines of ALS-FRS, FVC%, and MRC compound score were predictive of survival (P < 0.0001, P = 0.002, and P = 0.003, respectively). Future studies are needed to clarify whether nonspecific factors including muscle atrophy, dysphagia, and coexisting diseases influence prediction of survival in ALS patients. A more precise set of predictors may help to better stratify patient subgroups for future treatment trials.

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Section: Discussionmentioning

confidence: 98%

Disease progression in amyotrophic lateral sclerosis: Predictors of survival

et al. 2002

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“…The importance of excitotoxicity has been shown by other reports (Plaitakis and Caroscio, 1987; Rothstein et al, 1992; Rothstein et al, 1990). In fact, the effective compounds for ALS, including riluzole (Lacomblez et al, 1996; Meininger et al, 1997) and ceftriaxone (Berry et al, 2013; Rothstein et al, 2005), inhibit glutamate signaling at the agonist and receptor level, respectively. However, these drugs may also block physiological or basal glutamate signaling, which may hamper the normal functioning of neurons.…”

Section: Discussionmentioning

confidence: 99%

Transient mitochondrial permeability transition mediates excitotoxicity in glutamate-sensitive NSC34 D motor neuron-like cells

Liu¹,

Xu²,

Wang³

et al. 2015

Experimental Neurology

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Excitotoxicity plays a critical role in neurodegenerative disease. Cytosolic calcium overload and mitochondrial dysfunction are among the major mediators of high level glutamate-induced neuron death. Here, we show that the transient opening of mitochondrial permeability transition pore (tMPT) bridges cytosolic calcium signaling and mitochondrial dysfunction and mediates glutamate-induced neuron death. Incubation of the differentiated motor neuron-like NSC34D cells with glutamate (1 mM) acutely induces cytosolic calcium transient (30% increase). Glutamate also stimulates tMPT opening, as reflected by a 2-fold increase in the frequency of superoxide flash, a bursting superoxide production event in individual mitochondria coupled to tMPT opening. The glutamate-induced tMPT opening is attenuated by suppressing cytosolic calcium influx and abolished by inhibiting mitochondrial calcium uniporter (MCU) with Ru360 (100 µM) or MCU shRNA. Further, increased cytosolic calcium is sufficient to induce tMPT in a mitochondrial calcium dependent manner. Finally, chronic glutamate incubation (24 hr) persistently elevates the probability of tMPT opening, promotes oxidative stress and induces neuron death. Attenuating tMPT activity or inhibiting MCU protects NSC34D cells from glutamate-induced cell death. These results indicate that high level glutamate-induced neuron toxicity is mediated by tMPT, which connects increased cytosolic calcium signal to mitochondrial dysfunction.

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“…Riluzole was able to effectively reduce ischemic neuronal damage in the spinal cord (Lang-Lazdunski et al, 1999), and prevent motoneuron death in vitro after exposure to glutamate agonists (Estevez et al, 1995). Moreover, clinical trials have proven that riluzole increased survival of a subset of amyotrophic lateral sclerosis (ALS) patients with bulbar onset, and it is one of the most promising drugs for the treatment of ALS (Bensimon et al, 1994;Gordon, 2005;Meininger et al, 1997). We have shown in our previous studies that systemic administration of riluzole in animals that had their lumbar ventral root avulsed and reimplanted prevented the death of motoneurons (Nó grá di and Vrbová , 2001), even if onset of treatment was delayed by 10 days (Nó grá di et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Increased Survival and Reinnervation of Cervical Motoneurons by Riluzole after Avulsion of the C7 Ventral Root

Pintér

Gloviczki²,

Szabó

et al. 2010

Journal of Neurotrauma

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Although adult motoneurons do not die if their axons are injured at some distance from the cell body, they are unable to survive injury caused by ventral root avulsion. Some of the injured motoneurons can be rescued if the ventral root is re-inserted into the spinal cord. Brachial plexus injuries that involve the complete or partial avulsion of one or more cervical ventral roots can be treated successfully only if satisfactory numbers of motoneurons remain alive following such an injury at the time of reconstructive surgery. Here we investigated the various strategies that could be used to rescue injured rat cervical motoneurons. The seventh cervical ventral root (C7) was avulsed and various therapeutic approaches were applied to induce motoneuronal survival and regeneration. Avulsion of the root without reimplantation resulted in very low numbers of surviving motoneurons (65 AE 8 SEM), while treatment of the injured motoneurons with riluzole resulted in high numbers of surviving motoneurons (637 AE 26 SEM). When the C7 ventral root was reimplanted or a peripheral nerve implant was used to guide the regenerating axons to a muscle, considerable numbers of motoneurons regenerated their axons (211 AE 15 SEM and 274 AE 28 SEM, respectively). Much greater numbers of axons regenerated when reimplantation was followed by riluzole treatment (573 AE 9 SEM). These results show that injured adult motoneurons can be rescued by riluzole treatment, even if they cannot regenerate their axons. Reinnervation of the peripheral targets can also be further improved with riluzole treatment.

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The Riluzole Early Access Programme: descriptive analysis of 844 patients in France

Cited by 20 publications

References 8 publications

Disease progression in amyotrophic lateral sclerosis: Predictors of survival

Disease progression in amyotrophic lateral sclerosis: Predictors of survival

Transient mitochondrial permeability transition mediates excitotoxicity in glutamate-sensitive NSC34 D motor neuron-like cells

Increased Survival and Reinnervation of Cervical Motoneurons by Riluzole after Avulsion of the C7 Ventral Root

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