Prophylactic neuroprotection with A91 improves the outcome of spinal cord injured rats

Ibarra, Antonio; Sosa, Maria J; García, Elisa; Flores, Adrian; Cruz, Yolanda; Mestre, Humberto; Martiñón, S.; Pineda-Rodríguez, B.A.; Gutiérrez‐Ospina, Gabriel

doi:10.1016/j.neulet.2013.08.048

Cited by 15 publications

(13 citation statements)

References 20 publications

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“…These results were consistent throughout several SCI preclinical studies. Also it was noted that motor recovery had a direct correlation with neuronal survival, myelin preservation, and apoptosis reduction in treated groups [102,107,109,110,114,117,118]. As a consequence of these encouraging results, we have envisioned the possibility of combining this strategy with others that have also shown beneficial effects [103, 117, unpublished data].…”

Section: The Altered Peptide Ligand A91 As a Potential Treatment For mentioning

confidence: 97%

Protective Role of the Immune System in Spinal Cord Injury: Immunomodulation with Altered Peptide Ligands

Suárez‐Meade¹,

Ibarra²

2016

Recovery of Motor Function Following Spinal Cord Injury

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Spinal cord injury SCI is a phenomenon characterized by damage to the spinal cord and nerve roots, resulting in loss of physiological activity below the lesion. Injury to the spinal cord activates a cascade of cellular and molecular reactions in which the immune system plays an essential role, as there is an uncontrolled immune response that endows further damage to neural tissue. However, the activity of immune system at the site of injury can be modified in order to obtain a neuroprotective environment and promote SCI recovery. This strategy has been designed under the light of the innovative concept protective autoimmunity P" and can be stimulated with the use of altered peptide ligands "PL . "dequate immunomodulation with "PL can be obtained with the peptide " , which is a safe synthetic peptide derived from the myelin basic protein M"P that has proven to be effective in preclinical research. Immunization with " is carried out with the objective of preventing further damage and promoting neuroprotection. This peptide has direct influence over SCI secondary mechanisms such as inflammation, lipid peroxidation, and apoptosis. Preclinical results suggest that immunization with " could be an effective treatment in the clinical field, providing a better quality of life to SCI patients.

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Section: The Altered Peptide Ligand A91 As a Potential Treatment For mentioning

confidence: 97%

Protective Role of the Immune System in Spinal Cord Injury: Immunomodulation with Altered Peptide Ligands

Suárez‐Meade¹,

Ibarra²

2016

Recovery of Motor Function Following Spinal Cord Injury

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“…The effect of the immunization is preserved in the chronic stage of the lesion and as a prophylactic treatment or up to 72 h after the SCI; however, it diminishes when applied to lesions due to severe contusion or complete medullar cut and is eliminated with a double immunization. It has also been determined that the severity of the lesion determines the profile of genetic expression in the lesion after immunization and that immunization plus the removal of the fibroglial scar and/or the implant of a scaffold as support for mesenchymal stem cells favors a permissive microenvironment for motor recovery and improves the electrophysiological activity in the chronic stage after a complete section of the spinal cord [67][68][69][70][71][72][73]. The protective response of A91 is between 4 and 6 days, indicating that it acts on subsequent mechanisms to the acute stage.…”

Section: A91 Peptidementioning

confidence: 99%

Current Developments in Antioxidant Therapies for Spinal Cord Injury

Villa¹,

Villamar²,

Zapien³

et al. 2019

Spinal Cord Injury Therapy [Working Title]

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When spinal cord injury (SCI) occurs, numerous sources of reactive oxygen species and nitrogen species may be active within first minutes or hours and even reactivate few days later. Free radical formation and lipid peroxidation (LP) have been described as an important mechanism in the beginning and accelerated progress in the development of diverse pathologies, importantly in those related to central nervous system. The compromise of molecules and cellular structures due to the oxidative state of microenvironment in SCI may determinate survival or apoptosis of resident and infiltrating cells and polarization toward an inflammatory response, which lead to an extension of damaged tissue and loss of neuronal function, or a regulatory/regenerative response. The investigation of new antioxidant agents and their action at a molecular level begins to reveal mechanisms that, if correctly modulated, promise an improvement in recovery of functions with respect to conventional pharmacological therapies. In this chapter, we will review the general mechanisms of oxidative stress and lipid peroxidation, those antioxidant treatments in experimental development and clinical phase, as well as their achievements and limitations.

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“…La inoculación se lleva a cabo mediante una punción intradérmica en la base de la cola (Martiñón et al, 2007). En todos los estudios se evalúa el efecto de la terapia mediante estudios morfológicos (preservación del tejido, axones mielinizados o sobrevida de neuronas) y pruebas clínicas que analizan la recuperación motora, específicamente la capacidad de movimiento de las extremidades posteriores del animal (Hauben et al, 2000;Ibarra et al, 2013;Martiñon et al, 2007). Esta evaluación se lleva a cabo mediante pruebas de locomoción a campo abierto o pruebas de cinemática (Collazos-Castro, López-Dolado y Nieto-Sampedro, 2006;Basso et al, 2006).…”

Section: Desarrollo De Una Vacuna Preclínicaunclassified

“…En la línea de estudio para conocer las alternativas terapéuticas que puede ofrecer esta terapia innovadora, se ha demostrado incluso que la estimulación profiláctica de la ap (inmunización con A91 antes de la lme) puede provocar una mejor recuperación motora después de una lme (Ibarra et al, 2013). Éste es un hallazgo muy importante, ya que también sustenta la propuesta de un tratamiento profiláctico para los casos en que se programa un procedimiento quirúrgico de riesgo en columna vertebral y que pudiera lesionar la médula espinal.…”

Section: Desarrollo De Una Vacuna Preclínicaunclassified

“…Después de más de una década de trabajo con A91, los estudios han demostrado que este péptido, además de promover neuroprotección, también incrementa la recuperación motora (Ibarra et al, 2004;Martiñón et al, 2007;García et al, 2012;Rodríguez-Barrera et al, 2013;Ibarra et al, 2010;Ibarra et al, 2013). El éxito de esta terapia en modelos animales abre un panorama muy prometedor para su aplicación a nivel clínico.…”

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Untitled

2015

EDSC

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La lesión de la médula espinal (lme) es un fenómeno que daña al sistema nervioso central (snc), y produce la pérdida de la actividad fisiológica por debajo del sitio de la lesión. Actualmente no existe algún tratamiento efectivo para la lme en el campo clínico. El papel del sistema inmune a través de la autorreactividad protectora (ap)-un fenómeno fisiológico desarrollado después de la lme-puede ser de gran importancia para inducir neuroprotección. La ap puede estimularse con el uso de péptidos neurales modificados (pnm) procedentes de componentes neurales como la proteína básica de la mielina. El presente artículo pretende dar una visión general de esta estrategia terapéutica innovadora que ofrece efectos benéficos y un futuro muy alentador. Se revisará el fundamento, los mecanismos y los hallazgos preclínicos más importantes utilizando el pnm a91. Finalmente, se comentarán los obstáculos a vencer para su aplicación clínica. Palabras clave: lesión de médula espinal, ligadura de peptídico modificado, neuroprotección, autorreactividad protectora, inmunomodulación.

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Prophylactic neuroprotection with A91 improves the outcome of spinal cord injured rats

Cited by 15 publications

References 20 publications

Protective Role of the Immune System in Spinal Cord Injury: Immunomodulation with Altered Peptide Ligands

Protective Role of the Immune System in Spinal Cord Injury: Immunomodulation with Altered Peptide Ligands

Current Developments in Antioxidant Therapies for Spinal Cord Injury

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