RT Journal Article
T1 ApTOLL: A new therapeutic aptamer for cytoprotection and (re)myelination after multiple sclerosis
A1 Fernández-Gómez, Beatriz
A1 Marchena, Miguel A
A1 Piñeiro, David
A1 Gómez-Martín, Paula
A1 Sánchez, Estefanía
A1 Laó, Yolanda
A1 Valencia, Gloria
A1 Nocera, Sonia
A1 Benítez-Fernández, Rocío
A1 Castaño-León, Ana M
A1 Lagares, Alfonso
A1 Hernández Jiménez, Macarena
A1 Castro, Fernando de
AB 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.
SN 0007-1188
YR 2023
FD 2023-09
LK https://hdl.handle.net/20.500.14352/113252
UL https://hdl.handle.net/20.500.14352/113252
LA eng
NO Fernández-Gómez B, Marchena MA, Piñeiro D, Gómez-Martín P, Sánchez E, Laó Y, Valencia G, Nocera S, Benítez-Fernández R, Castaño-León AM, Lagares A, Hernández-Jiménez M, de Castro F. ApTOLL: A new therapeutic aptamer for cytoprotection and (re)myelination after multiple sclerosis. Br J Pharmacol. 2024 Sep;181(17):3263-3281. doi: 10.1111/bph.16399. Epub 2024 May 14. PMID: 38742374.
DS Docta Complutense
RD 13 abr 2025