GEMALS: A promising therapy for amyotrophic lateral sclerosis

Geffard,Michel; Mangas,Arturo; Bedat,Denis; Coveñas,Rafael

doi:10.3892/etm.2018.5868

GEMALS: A promising therapy for amyotrophic lateral sclerosis

Authors:
- Michel Geffard
- Arturo Mangas
- Denis Bedat
- Rafael Coveñas
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Affiliations: Research Department, Institute for Development of Research on Human Pathology and Therapeutics, 33400 Talence, France, Institute of Neurosciences of Castilla y León, Laboratory of Neuroanatomy of The Peptidergic Systems, University of Salamanca, 37007 Salamanca, Spain
Published online on: February 14, 2018 https://doi.org/10.3892/etm.2018.5868
Pages: 3203-3210
Copyright: © Geffard et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that currently has no cure. At present, the only approved treatment for ALS is Riluzole, a glutamate release blocker that improves life expectancy by 3‑6 months. ALS-Endotherapia (GEMALS) is a novel therapeutic approach to treat ALS and the aim of the present study was to investigate the potential beneficial effects of this novel treatment. A total of 31 patients with ALS were assessed in the current study. Deceleration of the disease was observed in 83.87% (P<0.0001) of patients and mean life expectancy was increased by 38 months. Motor functions, including breathing, walking, salivation, speech, swallowing and writing, were also improved in patients treated with GEMALS. The results of the present study demonstrate that long‑term treatment with GEMALS has a curative effect in patients with ALS. Furthermore, the overall effectiveness of GEMALS was assessed using the ALS Assessment Questionnaire. The score improvement was 76.2 and 100% for men and women, respectively (P<0.0001), compared with the worldwide reference score. The present study provides a promising basis for the use of GEMALS as a therapeutic treatment for patients with ALS; however, these results must be confirmed in a double‑blinded and randomized clinical trial.

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1	Shamshiri H, Fatehi F, Abolfazli R, Harirchian MH, Sedighi B, Zamani B, Roudbari A, Razazian N, Khamseh F and Nafissi S: Trends of quality of life changes in amyotrophic lateral sclerosis patients. J Neurol Sci. 368:35–40. 2016. View Article : Google Scholar : PubMed/NCBI
2	Jenkinson C, Norquist JM and Fitzpatrick R: Deriving summary indices of health status from the amyotrophic lateral sclerosis assessment questionnaires (ALSAQ-40 and ALSAQ-5). J Neurol Neurosurg Psychiatry. 74:242–245. 2003. View Article : Google Scholar : PubMed/NCBI
3	Boillée S and Lobsiger CS: Glial cells not that supportive for motor neurons. Med Sci (Paris). 24:124–126. 2008.(In French). View Article : Google Scholar : PubMed/NCBI
4	Bensimon G, Lacomblez L and Meininger V: A controlled trial of Riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. New J Eng Med. 330:585–591. 1994. View Article : Google Scholar
5	Traynor BJ, Alexander M, Corr B, Frost E and Hardiman O: An outcome study of riluzole in amyotrophic lateral sclerosis - a population-based study in Ireland, 1996–2000. J Neurol. 250:473–479. 2003. View Article : Google Scholar : PubMed/NCBI
6	Meininger V, Lacomblez L and Salachas F: What has changed with riluzole? J Neurol. 247:19–22. 2000. View Article : Google Scholar : PubMed/NCBI
7	Rossi S: Australian medicines handbook. Australian Med Handbook Unit Trust Adelaide. 2013.
8	Ascherio A, Weisskopf MG, O'reilly EJ, Jacobs EJ, McCullough ML, Calle EE, Cudkowicz M and Thun MJ: Vitamin E intake and risk of amyotrophic lateral sclerosis. Ann Neurol. 57:104–110. 2005. View Article : Google Scholar : PubMed/NCBI
9	Jones SP, Guillemin GJ and Brew BJ: The kynurenine pathway in stem cell biology. Int J Tryptophan Res. 6:57–66. 2013. View Article : Google Scholar : PubMed/NCBI
10	Geffard M, de Bisschop L, Duleu S, Hassaine N, Mangas A and Coveñas R: Endotherapia: A new frontier in the treatment of multiple sclerosis and other chronic diseases. Discov Med. 10:443–451. 2010.PubMed/NCBI
11	Geffard M, de Bisschop L, Duleu S, Pouns O, Ferran G, Bessede A, Hassaine N, Autran JL, Bodet D, Mangas A and Covenas R: Endotherapia. Antiinflamm Antiallergy Agents Med Chem. 9:197–211. 2010. View Article : Google Scholar
12	Nicaise C, Coupier J, Dabadie MP, De Decker R, Mangas A, Bodet D, Poncelet L, Geffard M and Pochet R: Gemals, a new drug candidate, extends lifespan and improves electromyographic parameters in a rat model of amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 9:85–90. 2008. View Article : Google Scholar : PubMed/NCBI
13	Geffard M, Duleu S, Bessede A, Vigier V, Bodet D, Mangas A and Coveñas R: GEMSP: A new therapeutic approach of multiple sclerosis. Cent Nerv Syst Agents Med Chem. 12:173–181. 2012. View Article : Google Scholar : PubMed/NCBI
14	Mangas A, Covenas R, Bodet D, Dabadie MP, Glaize G and Geffard M: Evaluation of the effects of a new drug on brain leukocyte infiltration in an experimental model of autoimmune encephalomyelitis. Lett Drug Des Discov. 3:138–148. 2006. View Article : Google Scholar
15	Mangas A, Coveñas R, Bodet D, de León M, Duleu S and Geffard M: Evaluation of the effects of a new drug candidate (GEMSP) in a chronic EAE model. Int J Biol Sci. 4:150–160. 2008. View Article : Google Scholar : PubMed/NCBI
16	Mangas A, Coveñas R, Bodet D, Duleu S and Geffard M: A new drug candidate (GEMSP) for multiple sclerosis. Curr Med Chem. 16:3203–3214. 2009. View Article : Google Scholar : PubMed/NCBI
17	Couratier P, Marin B, Laurette G, Nicol M and Preux PM: Epidemiologie, clinical spectrum of ALS and differential diagnoses. Presse Med. 43:538–548. 2014.(In French). View Article : Google Scholar : PubMed/NCBI
18	Kimura F, Fujimura C, Ishida S, Nakajima H, Furutama D, Uehara H, Shinoda K, Sugino M and Hanafusa T: Progression rate of ALSFRS-R at time of diagnosis predicts survival time in ALS. Neurology. 66:265–267. 2006. View Article : Google Scholar : PubMed/NCBI
19	Labra J, Menon P, Byth K, Morrison S and Vucic S: Rate of disease progression: A prognostic biomarker in ALS. J Neurol Neurosurg Psychiatry. 87:628–632. 2016. View Article : Google Scholar : PubMed/NCBI
20	Jenkinson C, Fitzpatrick R, Brennan C, Bromberg M and Swash M: Development and validation of a short measure of health status for individuals with amyotrophic lateral sclerosis/motor neurone disease: The ALSAQ-40. J Neurol. 3 246 Suppl:III16–III21. 1999. View Article : Google Scholar
21	Jenkinson C, Fitzpatrick R, Brennan C and Swash M: Evidence for the validity and reliability of the ALS assessment questionnaire: The ALSAQ-40. Amyotroph Lateral Scler Other Motor Neuron Disord. 1:33–40. 1999. View Article : Google Scholar : PubMed/NCBI
22	Dolfi SC, Medina DJ, Kareddula A, Paratala B, Rose A, Dhami J, Chen S, Ganesan S, Mackay G, Vazquez A and Hirshfield KM: Riluzole exerts distinct antitumor effects from a metabotropic glutamate receptor 1-specific inhibitor on breast cancer cells. Oncotarget. 8:44639–44653. 2017. View Article : Google Scholar : PubMed/NCBI
23	El Idrissi A: Taurine increases mitochondrial buffering of calcium: Role in neuroprotection. Amino Acids. 34:321–328. 2008. View Article : Google Scholar : PubMed/NCBI
24	Mangas A, Coveñas R and Geffard M: New drug therapies for multiple sclerosis. Curr Opin Neurol. 23:287–292. 2010. View Article : Google Scholar : PubMed/NCBI
25	Gaydess A, Duysen E, Li Y, Gilman V, Kabanov A, Lockridge O and Bronich T: Visualization of exogenous delivery of nanoformulated butyrylcholinesterase to the central nervous system. Chem Biol Interact. 187:295–298. 2010. View Article : Google Scholar : PubMed/NCBI
26	Wang Z, Zhu H, Li D and Yang X: Preparation and application of single polyelectrolyte microcapsules possessing tunable autofluorescent properties. Colloids Surfaces A: Physicochem Eng Aspects. 329:58–66. 2008. View Article : Google Scholar
27	Blondeau N, Widmann C, Lazdunski M and Heurteaux C: Polyunsaturated fatty acids induce ischemic and epileptic tolerance. Neuroscience. 109:231–241. 2002. View Article : Google Scholar : PubMed/NCBI
28	Yoshida H, Yanai H, Namiki Y, Fukatsu-Sasaki K, Furutani N and Tada N: Neuroprotective effects of edaravone: A novel free radical scavenger in cerebrovascular injury. CNS Drug Rev. 12:9–20. 2006. View Article : Google Scholar : PubMed/NCBI
29	Crouzin N, de Jesus Ferreira MC, Cohen-Solal C, Aimar RF, Vignes M and Guiramand J: Alpha-tocopherol-mediated long-lasting protection against oxidative damage involves an attenuation of calcium entry through TRP-like channels in cultured hippocampal neurons. Free Radic Biol Med. 42:1326–1337. 2007. View Article : Google Scholar : PubMed/NCBI
30	Qiu S, Li L, Weeber EJ and May JM: Ascorbate transport by primary cultured neurons and its role in neuronal function and protection against excitotoxicity. J Neurosci Res. 85:1046–1056. 2007. View Article : Google Scholar : PubMed/NCBI
31	Wang WP, Iyo AH, Miguel-Hidalgo J, Regunathan S and Zhu MY: Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons. Brain Res. 1084:210–216. 2006. View Article : Google Scholar : PubMed/NCBI
32	Agar J and Durham H: Relevance of oxidative injury in the pathogenesis of motor neuron diseases. Amyotroph Lateral Scler Other Motor Neuron Disord. 4:232–242. 2003. View Article : Google Scholar : PubMed/NCBI
33	Kumari N, Prentice H and Wu JY: Taurine and its neuroprotective role. Adv Exp Med Biol. 775:19–27. 2013. View Article : Google Scholar : PubMed/NCBI