Evaluation of the Effects of a New Drug on Brain Leukocyte Infiltration in an Experimental Model of Autoimmune Encephalomyelitis

Mangas, A.; Coveñas, Rafael; Bodet, D.; Dabadie, M.P.; Glaize, G; Geffard, M.

doi:10.2174/157018006776286943

Cited by 9 publications

(32 citation statements)

References 22 publications

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“…, vitamins) coupled to PLL represent a low weight proportion of the whole PLL-compound molecular weight; iii) PLL compounds are not transporters of small molecules (they are not neither vectors nor liposomes); it should be noted that free constituents (small molecules not linked to PLL) have no effect since they are quickly incorporated into the metabolism and only PLL-compounds have a beneficial effect as previously reported; 12,52 in sum, PLL-compounds have an effect only when small molecules are linked to the PLL and neither free small molecules nor PLL alone have effect; 12,52 and iv) free small molecules are quickly degraded or incorporated to metabolism, but when they are linked to PLL the half-life is longer as well as their effects; for this reason the dose of PLL compounds is much lower than currently standard drugs.…”

Section: Discussionmentioning

confidence: 77%

Gemst: a taylor-made combination that reverts neuroanatomical changes in stroke

Mangas

Yajeya

González³

et al. 2017

Eur J Histochem

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In a single transient middle cerebral artery occlusion model of stroke and using immunohistochemical techniques, the effects of a new therapeutic approach named Gemst (a member of the Poly-LLysine innovative therapies) have been studied in the rat brain. The expression of inflammatory (CD45, CD11b), oxidative (NO-tryptophan, NO2-tyrosine) and indoleamine 2, 3-dioxygenase pathway (kynurenic acid, 3-hydroxy anthranilic acid) markers has been evaluated in early and late phases of stroke. For this purpose, we have developed eight highly specific monoclonal antibodies directed against some of these markers. In the early phase (3 and 5 days of the stroke, we observed no effect of Gemst treatment (7.5 mg/day, subcutaneously for 3, 5 days). In the late phase (21 days) of stroke and exclusively in the ipsilateral side of non-treated animals an overexpression of kynurenic acid, 3- hydroxy anthranilic acid, CD45, CD11b, GFAP and ionized calcium-binding adapter molecule 1 (IBA-1) was found. In treated animals, the overexpression of the four former markers was completely abolished whereas the overexpression of the two latter ones was decreased down to normal levels. Gemst reversed the pathological conditions of stroke to normal situations. Gemst exerts a multifunctional action: down-regulates the indoleamine 2, 3-dioxygenase pathway and abolishes brain infiltration, microglial activation and gliosis. Moreover, Gemst has no effect on the expression of doublecortin, a protein involved in neuronal migration. Gemst could be a new drug for the treatment of stroke since it reverses the pathological findings of stroke and normalizes brain tissue conditions following the ischemic insult.

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Section: Discussionmentioning

confidence: 77%

Gemst: a taylor-made combination that reverts neuroanatomical changes in stroke

Mangas

Yajeya

González³

et al. 2017

Eur J Histochem

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“…In addition, many studies have shown the therapeutic effects of vitamins. Thus, (1) vitamin K has been used as a possible therapy in an animal model of multiple sclerosis [91], (2) populations with a regular intake of vitamin E have a lower risk of amyotrophic lateral sclerosis than nonuser populations [92], (3) α-tocopherol succinate is a component of GEMSP owing to its interactions with ROS and NO [93], and (4) a vitamin A metabolite (all-trans retinoic acid) has been shown to exert a therapeutic effect in an experimental autoimmune nephritis model [94]. The possible therapeutic implications of vitamins open new perspectives as regards the involvement of such substances in neurodegenerative diseases.…”

Section: Possible Functional Roles Of Vitaminsmentioning

confidence: 99%

Frontiers in Vitamin Research: New Antibodies, New Data

Coveñas

Mangas

Bodet³

et al. 2011

The Scientific World JOURNAL

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Since 2004, the anatomical distribution of vitamins in the monkey brain, studied using immunohistochemical techniques and new tools (specific antisera that discriminate different vitamins reasonably well), has been an ongoing research field. The visualization of immunoreactive structures containing vitamins (folic acid, riboflavin, thiamine, pyridoxal, and vitamin C) has recently been reported in the monkey brain (Macaca fascicularis), all these vitamins showing a restricted or very restricted distribution. Folic acid, thiamine, and riboflavin have only been observed in immunoreactive fibers, vitamin C has only been found in cell bodies (located in the primary somatosensory cortex), and pyridoxal has been found in both fibers and cell bodies. Perikarya containing pyridoxal have been observed in the paraventricular hypothalamic nucleus, the periventricular hypothalamic region, and in the supraoptic nucleus. The fibers containing vitamins are thick, smooth (without varicosities), and are of medium length or long, whereas immunoreactive cell bodies containing vitamins are round or triangular. At present, there are insufficient data to elucidate the roles played by vitamins in the brain, but the anatomical distribution of these compounds in the monkey brain provides a general idea (although imprecise and requiring much more study) about the possible functional implications of these molecules. In this sense, here the possible functional roles played by vitamins are discussed.

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“…In preclinical studies (acute model of EAE) (10), it has been reported that GEMSP (0.75 mg/day) inhibited brain leukocyte infiltration (10). Later, in a chronic model of EAE, it was demonstrated that GEMSP (7.5 mg/day) abolished EAE episodes, the clinical score and brain leukocyte infiltration.…”

Section: Discussionmentioning

confidence: 99%

“…The beneficial effects of GEMSP have been demonstrated in acute and chronic experimental autoimmune encephalomyelitis (EAE) models (10,11).…”

Section: Introductionmentioning

confidence: 99%

Follow-up of multiple sclerosis patients treated with Endotherapia (GEMSP)

Geffard¹,

Mangas²,

Coveñas

2017

Biomedical Reports

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Abstract. Endotherapia (GEMSP) is a novel therapeutic approach for multiple sclerosis (MS). The aim of the present study was to demonstrate the efficiency of Endotherapia in the follow-up of 193 patients with MS. The efficiency coefficient that was evaluated was the Expanded Disability Status Scale (EDSS) score, which is a functional scale of MS progression. The evaluated score of each patient during follow-up visits was compared with the theoretical score of the disease progression without GEMSP. The evolution of the EDSS score was evaluated according to the inclusion score. The quantitative global study of the EDSS score highlighted a statistically significant difference between the final average scores of the treatment with GEMSP (M) and worldwide reference (R) groups. The improvement of the M group compared with the R group was 24.5%. According to the final EDSS scores, the study highlighted a difference in favor of the M group with 62.0% for scores ≤3, 7.8% for scores between 3 and 6 and 19.6% for scores ≥6. According to the qualitative evolution of the EDSS scores, the improvements in favor of group M were 49.3% for scores ≤3, 79.1% for scores between 3 and 6 and 19.5% for scores ≥6. The qualitative study of the EDSS score showed a statistically significant success percentage; the success percentages were between 59.1 and 90.0%. In a larger population of MS patients, the data confirm the beneficial effects of GEMSP that were previously reported in pre-clinical and clinical studies. In addition, 78% of patients showed an improvement or deceleration of the disease.

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Evaluation of the Effects of a New Drug on Brain Leukocyte Infiltration in an Experimental Model of Autoimmune Encephalomyelitis

Cited by 9 publications

References 22 publications

Gemst: a taylor-made combination that reverts neuroanatomical changes in stroke

Gemst: a taylor-made combination that reverts neuroanatomical changes in stroke

Frontiers in Vitamin Research: New Antibodies, New Data

Follow-up of multiple sclerosis patients treated with Endotherapia (GEMSP)

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