RESUMEN
Amyotrophic lateral sclerosis (ALS) is a progressive and rapidly fatal neurodegenerative disease in which both upper and lower motoneurones are involved. The recent discovery of mutations affecting the superoxide dismutase (SOD) gene has given impetus to research on the role of oxidative stress in the pathogenesis of familial ALS, while further evidence for a role of excitotoxicity in the disease process has arisen. In this review, Erik Louvel, Jacques Hugon and Adam Doble discuss these findings and, in addition, describe how a number of large, well-controlled clinical trials have taken place to test potential therapies suggested by different aetiological hypotheses, including immunosuppressive therapies, neurotrophic factors, antioxidants and anti-excitotoxic drugs. These trials have led to the first modest steps in the treatment of this devastating neurological disease.
Asunto(s)
Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Superóxido Dismutasa/genética , Esclerosis Amiotrófica Lateral/enzimología , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/fisiopatología , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Ensayos Clínicos como Asunto/tendencias , Modelos Animales de Enfermedad , Antagonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Aminoácidos Excitadores/uso terapéutico , Radicales Libres/efectos adversos , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/genética , Humanos , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Mutación/genética , Factores de Crecimiento Nervioso/farmacología , Factores de Crecimiento Nervioso/uso terapéutico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Estrés OxidativoRESUMEN
Amyotrophic lateral sclerosis (ALS) is a neurological disorder neuropathologically characterized by a progressive degeneration of upper and lower motoneurons. The origin of the neuronal death is presently unknown but recent findings suggest that neurodegeneration could be related to an excitotoxic disorder. We have recently shown that the cerebrospinal fluid (CSF) of ALS patients contains for neurones in cultures cytotoxic factors whose toxic properties are mediated by AMPA/kainate receptors, a subgroup of glutamate post-synaptic receptors. This study reports that riluzole partially prevents in vitro the neuronal degeneration produced by ALS CSF (neuronal survival 60.6 +/- 13.1%). Riluzole (5 x 10(-7) M) which reduces excitatory amino acid release, could represent a new pharmacological agent susceptible to be proposed to patients affected by this dramatic neurological disease.
Asunto(s)
Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Antagonistas de Aminoácidos Excitadores , Neuronas/efectos de los fármacos , Neurotoxinas/antagonistas & inhibidores , Tiazoles/farmacología , Animales , Células Cultivadas , Humanos , Neurotoxinas/toxicidad , Ratas , Receptores de Glutamato/efectos de los fármacos , Riluzol , Tiazoles/toxicidadRESUMEN
In the present study, clinical interview, Visual Evoked Potentials, psychological tests, TRH test, plasmatic MHPG dosage were investigated in 30 depressed patients with major depressive disorders. All the explorations were realised before and after 28 days of an antidepressant treatment. Thanks to analysis we found out the value of psychological tests. The study of evoked potentials brings to light the existence of electrophysiological variables, subordinate to the clinical state. On the contrary, "TRH Test" does not give us any useful indication, and plasmatic MOPEG dosage, although it confirms the existence of two groups of depressed patients, does not suggest any relationship with evolutive types.