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Recent Advances in Amyotrophic Lateral Sclerosis Research: Perspectives for Personalized Clinical Application

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Journal EPMA J
Date 2012 Dec 4
PMID 23199069
Citations 9
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Abstract

Treatment of amyotrophic lateral sclerosis (ALS) has been fueled, in part, by frustration over the shortcomings of the symptomatic drugs available, since these do not impede the progression of this disease. Currently, over 150 different potential therapeutic agents or strategies have been tested in preclinical models of ALS. Unfortunately, therapeutic modifiers of murine ALS have failed to be successfully translated into strategies for patients, probably because of differences in pharmacokinetics of the therapeutic agents, route of delivery, inefficiency of the agents to affect the distinct pathologies of the disease or inherent limitations of the available animal models. Given the multiplicity of the pathological mechanisms implicated in ALS, new therapies should consider the simultaneous manipulation of multiple targets. Additionally, a better management of ALS therapy should include understanding the interactions between potential risk factors, biomarkers and heterogeneous clinical features of the patients, aiming to manage their adverse events or personalize the safety profile of these agents. This review will discuss novel pharmacological approaches concerning adjusted therapy for ALS patients: iron-binding brain permeable multimodal compounds, genetic manipulation and cell-based treatment.

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References
1.
Molz S, Decker H, Dal-Cim T, Cremonez C, Cordova F, Leal R . Glutamate-induced toxicity in hippocampal slices involves apoptotic features and p38 MAPK signaling. Neurochem Res. 2007; 33(1):27-36. DOI: 10.1007/s11064-007-9402-1. View

2.
Weinreb O, Amit T, Mandel S, Youdim M . Neuroprotective molecular mechanisms of (-)-epigallocatechin-3-gallate: a reflective outcome of its antioxidant, iron chelating and neuritogenic properties. Genes Nutr. 2009; 4(4):283-96. PMC: 2775893. DOI: 10.1007/s12263-009-0143-4. View

3.
Cho G, Noh M, Kim H, Koh S, Kim K, Kim S . Bone marrow-derived stromal cells from amyotrophic lateral sclerosis patients have diminished stem cell capacity. Stem Cells Dev. 2009; 19(7):1035-42. DOI: 10.1089/scd.2009.0453. View

4.
Wang X, Lee S, Simmons Z, Boyer P, Scott K, Liu W . Increased incidence of the Hfe mutation in amyotrophic lateral sclerosis and related cellular consequences. J Neurol Sci. 2004; 227(1):27-33. DOI: 10.1016/j.jns.2004.08.003. View

5.
Engelhardt J, Soos J, Obal I, Vigh L, Siklos L . Subcellular localization of IgG from the sera of ALS patients in the nervous system. Acta Neurol Scand. 2005; 112(2):126-33. DOI: 10.1111/j.1600-0404.2005.00445.x. View