OBJECTIVES: There is currently no effective pharmacological treatment for amyotrophic lateral sclerosis (ALS). In a transgenic mouse model of ALS, intrathecal infusion of insulin-like growth factor (IGF)-1 showed a promising increase in survival. We performed a double-blind clinical trial to assess the effect of intrathecal administration of IGF-1 on disease progression in patients with ALS. METHODS:Nine patients with ALS were randomly assigned to receive either a high dose (3 microg/kg of body weight) or low dose (0.5 microg/kg of body weight) of IGF-1 every 2 weeks for 40 weeks. The outcome measurements were the rate of decline of bulbar and limb functions (Norris scales) and forced vital capacity. RESULTS: The high-dose treatment slowed a decline of motor functions of the ALS patients in total Norris and limb Norris scales, but not in bulbar Norris or vital capacity. The intrathecal administration of IGF-1 had a modest but significant beneficial effect in ALS patients without any serious adverse effects. DISCUSSION: Intrathecal IGF-1 treatment could provide an effective choice for ALS although further studies in more patients are needed to confirm its efficacy and optimize dosages of IGF-1.
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OBJECTIVES: There is currently no effective pharmacological treatment for amyotrophic lateral sclerosis (ALS). In a transgenic mouse model of ALS, intrathecal infusion of insulin-like growth factor (IGF)-1 showed a promising increase in survival. We performed a double-blind clinical trial to assess the effect of intrathecal administration of IGF-1 on disease progression in patients with ALS. METHODS: Nine patients with ALS were randomly assigned to receive either a high dose (3 microg/kg of body weight) or low dose (0.5 microg/kg of body weight) of IGF-1 every 2 weeks for 40 weeks. The outcome measurements were the rate of decline of bulbar and limb functions (Norris scales) and forced vital capacity. RESULTS: The high-dose treatment slowed a decline of motor functions of the ALSpatients in total Norris and limb Norris scales, but not in bulbar Norris or vital capacity. The intrathecal administration of IGF-1 had a modest but significant beneficial effect in ALSpatients without any serious adverse effects. DISCUSSION: Intrathecal IGF-1 treatment could provide an effective choice for ALS although further studies in more patients are needed to confirm its efficacy and optimize dosages of IGF-1.
Authors: Diego Pastor; Mari Carmen Viso-León; Jonathan Jones; Jesus Jaramillo-Merchán; Juan José Toledo-Aral; Jose M Moraleda; Salvador Martínez Journal: Stem Cell Rev Rep Date: 2012-06 Impact factor: 5.739
Authors: Diego Pastor; Mari Carmen Viso-León; Arancha Botella-López; Jesus Jaramillo-Merchan; Jose M Moraleda; Jonathan Jones; Salvador Martínez Journal: Stem Cells Dev Date: 2013-02-13 Impact factor: 3.272
Authors: Angelo C Lepore; Christine Haenggeli; Mehdi Gasmi; Kathie M Bishop; Raymond T Bartus; Nicholas J Maragakis; Jeffrey D Rothstein Journal: Brain Res Date: 2007-09-22 Impact factor: 3.252