RESUMEN

Injecting proteins into the central nervous system that stimulate neuronal growth can lead to beneficial effects in animal models of disease. In particular, glial cell line-derived neurotrophic factor (GDNF) has shown promise in animal and cell models of Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis (ALS). Here, systemic AAV9-GDNF was delivered via tail vein injections to young rats to determine whether this could be a safe and functional strategy to treat the SOD1G93A rat model of ALS and, therefore, translated to a therapy for ALS patients. We found that GDNF administration in this manner resulted in modest functional improvement, whereby grip strength was maintained for longer and the onset of forelimb paralysis was delayed compared to non-treated rats. This did not, however, translate into an extension in survival. In addition, ALS rats receiving GDNF exhibited slower weight gain, reduced activity levels and decreased working memory. Collectively, these results confirm that caution should be applied when applying growth factors such as GDNF systemically to multiple tissues.

Asunto(s)

Esclerosis Amiotrófica Lateral/terapia , Sistema Nervioso Central/fisiopatología , Factor Neurotrófico Derivado de la Línea Celular Glial/uso terapéutico , Neuronas Motoras/patología , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/fisiopatología , Animales , Sistema Nervioso Central/efectos de los fármacos , Dependovirus/genética , Modelos Animales de Enfermedad , Terapia Genética , Vectores Genéticos/genética , Vectores Genéticos/uso terapéutico , Factor Neurotrófico Derivado de la Línea Celular Glial/efectos adversos , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Fuerza de la Mano/fisiología , Humanos , Neuronas Motoras/metabolismo , Ratas , Médula Espinal/efectos de los fármacos , Médula Espinal/fisiopatología , Superóxido Dismutasa/genética