title: Gemals, a new drug candidate, extends lifespan and improves electromyographic parameters in a rat model of amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal disease involving selective and progressive degeneration and death of motor neurons. ALS is a multifactorial disease in which oxidative stress, glutamate excitotoxicity, intracellular aggregates, neurofilamentous disorganization, zinc excitotoxicity, mitochondrial damage, neuroinflammation, abnormalities in growth factors and apoptosis play a role. Any therapeutic approach to delay or stop the evolution of ALS should therefore ideally target these multiple pathways leading to motor neuron death. We have developed a combination therapy (Gemals) composed of functional polypeptides (fatty acids, free radical scavengers and amino acids linked to poly-L-lysine), chosen according to their known potentiality for regeneration or protection of neuronal components such as myelin, axon transport and mitochondria. We found that Gemals significantly extended lifespan and improved electromyographic parameters in a SOD1(G93A) rat model. The use of two drug concentrations indicated a possible dose dependence. These initial findings open the way to further investigation necessary to validate this new drug as a candidate for ALS treatment.
authors.affiliation: Laboratory of Histology, Neuroanatomy and Neuropathology, Université Libre de Bruxelles, Belgium.
authors.forename: Charles
authors.initials: C
authors.lastname: Nicaise
authors.forename: Jerome
authors.initials: J
authors.lastname: Coupier
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dabadie
authors.forename: Robert
authors.initials: R
authors.lastname: De Decker
authors.forename: Arturo
authors.initials: A
authors.lastname: Mangas
authors.forename: Dominique
authors.initials: D
authors.lastname: Bodet
authors.forename: Luc
authors.initials: L
authors.lastname: Poncelet
authors.forename: Michel
authors.initials: M
authors.lastname: Geffard
authors.forename: Roland
authors.initials: R
authors.lastname: Pochet
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000503:physiopathology*; D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004576:Electromyography / Q000187:drug effects*; D008136:Longevity / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects*; D011107:Polylysine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051381:Rats / Q000235:genetics; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D004338:Drug Combinations; C529678:gemals; D011107:Polylysine