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ApTOLL: A new therapeutic aptamer for cytoprotection and (re)myelination after multiple sclerosis.
Fernández-Gómez, Beatriz; Marchena, Miguel A; Piñeiro, David; Gómez-Martín, Paula; Sánchez, Estefanía; Laó, Yolanda; Valencia, Gloria; Nocera, Sonia; Benítez-Fernández, Rocío; Castaño-León, Ana M; Lagares, Alfonso; Hernández-Jiménez, Macarena; de Castro, Fernando.
Afiliación
  • Fernández-Gómez B; Instituto Cajal-CSIC, Madrid, Spain.
  • Marchena MA; AptaTargets SL, Madrid, Spain.
  • Piñeiro D; PhD Program in Neuroscience, Universidad Autónoma de Madrid-Cajal Institute, Madrid, Spain.
  • Gómez-Martín P; Instituto Cajal-CSIC, Madrid, Spain.
  • Sánchez E; Facultad HM de Ciencias de la Salud de la Universidad Camilo José Cela.
  • Laó Y; Instituto de Investigación Sanitaria HM Hospitales.
  • Valencia G; AptaTargets SL, Madrid, Spain.
  • Nocera S; Instituto Cajal-CSIC, Madrid, Spain.
  • Benítez-Fernández R; Instituto Cajal-CSIC, Madrid, Spain.
  • Castaño-León AM; Instituto Cajal-CSIC, Madrid, Spain.
  • Lagares A; Instituto Cajal-CSIC, Madrid, Spain.
  • Hernández-Jiménez M; Instituto Cajal-CSIC, Madrid, Spain.
  • de Castro F; Instituto Cajal-CSIC, Madrid, Spain.
Br J Pharmacol ; 181(17): 3263-3281, 2024 Sep.
Article en En | MEDLINE | ID: mdl-38742374
ABSTRACT
BACKGROUND AND

PURPOSE:

ApTOLL is an aptamer selected to antagonize toll-like receptor 4 (TLR4), a relevant actor for innate immunity involved in inflammatory responses in multiple sclerosis (MS) and other diseases. The currently available therapeutic arsenal to treat MS is composed of immunomodulators but, to date, there are no (re)myelinating drugs available in clinics. In our present study, we studied the effect of ApTOLL on different animal models of MS. EXPERIMENTAL

APPROACH:

The experimental autoimmune encephalomyelitis (EAE) model was used to evaluate the effect of ApTOLL on reducing the inflammatory component. A more direct effect on oligodendroglia was studied with the cuprizone model and purified primary cultures of murine and human oligodendrocyte precursor cells (OPCs) isolated through magnetic-activated cell sorting (MACS) from samples of brain cortex. Also, we tested these effects in an ex vivo model of organotypic cultures demyelinated with lysolecithin (LPC). KEY

RESULTS:

ApTOLL treatment positively impacted the clinical symptomatology of mice in the EAE and cuprizone models, which was associated with better preservation plus restoration of myelin and oligodendrocytes in the demyelinated lesions of animals. Restoration was corroborated on purified cultures of rodent and human OPCs. CONCLUSION AND IMPLICATIONS Our findings reveal a new therapeutic approach for the treatment of inflammatory and demyelinating diseases such as MS. The molecular nature of the aptamer exerts not only an anti-inflammatory effect but also neuroprotective and remyelinating effects. The excellent safety profile demonstrated by ApTOLL in animals and humans opens the door to future clinical trials in MS patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encefalomielitis Autoinmune Experimental / Aptámeros de Nucleótidos / Ratones Endogámicos C57BL / Esclerosis Múltiple Límite: Animals / Female / Humans Idioma: En Revista: Br J Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encefalomielitis Autoinmune Experimental / Aptámeros de Nucleótidos / Ratones Endogámicos C57BL / Esclerosis Múltiple Límite: Animals / Female / Humans Idioma: En Revista: Br J Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido