Epidural cell therapy reduces neurological sequelae severity in canine distemper survivors.

Abstract

BACKGROUND: Canine distemper has a high mortality rate in the acute phase, and survivors typically suffer irreversible, progressive neurological sequelae, due to demyelinating leukoencephalitis, under current treatment standards. Mesenchymal stromal cells (MSCs) are found in the adult organism and represent a promising alternative for treating central nervous system disorders by secreting trophic and immunomodulatory factors that reduce inflammation, protect neurons, and promote regeneration. The therapeutic action of MSCs is largely mediated by the secretion of trophic and immunomodulatory factors, including anti-inflammatory cytokines, anti-apoptotic proteins, and neurotrophins. METHODS: The objective of this study was to evaluate the effects of three epidurally administered doses of 1 million MSCs per kilogram of body weight at 30-day intervals in four dogs suffering neurological sequelae of canine distemper. Each animal was evaluated using an adapted application of the modified neurodisability scale (0-15 scale) and a quality-of-life questionnaire ranking behaviors (0-7 scale). RESULTS: Statistical analysis confirmed the significant effect of using multiple doses, and regression analysis revealed a significant influence of age and weight on treatment outcome. Additionally, a logistic regression predicting improvement over time was extrapolated from these results to help clinicians and owners make better-informed decisions regarding cellular therapy. Complete clinical remission of four of the five subcategories of the neurodisability score was achieved in all subjects, with one subject achieving full remission of myoclonus. CONCLUSIONS: These results indicate that epidural MSC administration progressively reduced sequelae severity and improved patient quality of life of the four canine distemper survivors that participated in this study, supporting the translation of cellular therapies into clinical practice.