Cladribine Preserves Normal Central Nervous System Cellular Activity and Promotes Neuroprotection to Oxidative Stress Damage
Eixarch, Herena (Vall d'Hebron Institut de Recerca (VHIR))
Calvo-Barreiro, Laura (Vall d'Hebron Institut de Recerca (VHIR))
Fissolo, Nicolás (Vall d'Hebron Institut de Recerca (VHIR))
Boschert, Ursula (Merck Healthcare KGaA)
Hervera Abad, Arnau (Vall d'Hebron Institut de Recerca (VHIR))
Comabella López, Manuel (Vall d'Hebron Institut de Recerca (VHIR))
Montalban, Xavier (Universitat Autònoma de Barcelona. Departament de Medicina)
Espejo, Carmen (Vall d'Hebron Institut de Recerca (VHIR))

Data:	2025
Resum:	Multiple sclerosis (MS) is a chronic neuroinflammatory and demyelinating disease that causes disability in patients. Cladribine is an oral treatment that is used in relapsing-remitting and active secondary progressive MS. T and B lymphocytes are especially sensitive to cladribine, which are transiently depleted upon short treatment courses. However, cladribine crosses the blood-brain barrier (BBB), supporting the hypothesis that cladribine may affect central nervous system (CNS)-resident cells. In this study, we used human primary cells and human cell lines to test the effect of cladribine, at therapeutic concentrations, on cells of the CNS. In these conditions, cladribine did not affect survival, proliferation and the capacity of producing cytokines of human microglial cells (HMC3 cell line) or primary human astrocytes but enhanced the production of oxygen reactive species in both cell types. The initial differentiation of primary human neuronal progenitor cells was impaired when continuously exposed to the maximum therapeutic concentration of cladribine, but not when lower concentrations were used. However, cladribine protected differentiated SH-SY5Y human neuroblastoma cell line from oxidative stress-related cell death. In conclusion, using different in vitro cell models, we demonstrate that cladribine maintains the normal function of CNS glia and protects neuronal cells from oxidative stress damage.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cladribine ; Multiple sclerosis ; Disease modifying treatment ; Central nervous system ; Immunomodulation ; Neuroprotection ; Neurodegeneration
Publicat a:	International journal of molecular sciences, Vol. 26, Num. 23 (November 2025) , art. 11311, ISSN 1422-0067

DOI: 10.3390/ijms262311311
PMID: 41373470

22 p, 3.0 MB

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