AUTHOR=Gouveia Débora , Correia Jéssica , Cardoso Ana , Carvalho Carla , Oliveira Ana Catarina , Almeida António , Gamboa Óscar , Ribeiro Lénio , Branquinho Mariana , Sousa Ana , Lopes Bruna , Sousa Patrícia , Moreira Alícia , Coelho André , Rêma Alexandra , Alvites Rui , Ferreira António , Maurício Ana Colette , Martins Ângela TITLE=Intensive neurorehabilitation and allogeneic stem cells transplantation in canine degenerative myelopathy JOURNAL=Frontiers in Veterinary Science VOLUME=10 YEAR=2023 URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2023.1192744 DOI=10.3389/fvets.2023.1192744 ISSN=2297-1769 ABSTRACT=Introduction

Degenerative myelopathy (DM) is a neurodegenerative spinal cord disease with upper motor neurons, with progressive and chronic clinical signs, similar to amyotrophic lateral sclerosis (ALS). DM has a complex etiology mainly associated with SOD1 gene mutation and its toxic role, with no specific treatment. Daily intensive rehabilitation showed survival time near 8 months but most animals are euthanized 6–12 months after clinical signs onset.

Methods

This prospective controlled blinded cohort clinical study aims to evaluate the neural regeneration response ability of DM dogs subjected to an intensive neurorehabilitation protocol with mesenchymal stem cells (MSCs) transplantation. In total, 13 non-ambulatory (OFS 6 or 8) dogs with homozygous genotype DM/DM and diagnosed by exclusion were included. All were allocated to the intensive neurorehabilitation with MSCs protocol (INSCP) group (n = 8) or to the ambulatory rehabilitation protocol (ARP) group (n = 5), which differ in regard to training intensity, modalities frequency, and MSCs transplantation. The INSCP group was hospitalized for 1 month (T0 to T1), followed by MSCs transplantation (T1) and a second month (T2), whereas the ARP group was under ambulatory treatment for the same 2 months.

Results

Survival mean time of total population was 375 days, with 438 days for the INSCP group and 274 for the ARP group, with a marked difference on the Kaplan–Meier survival analysis. When comparing the literature's results, there was also a clear difference in the one-sample t-test (p = 0.013) with an increase in time of approximately 70%. OFS classifications between groups at each time point were significantly different (p = 0.008) by the one-way ANOVA and the independent sample t-test.

Discussion

This INSCP showed to be safe, feasible, and a possibility for a long progression of DM dogs with quality of life and functional improvement. This study should be continued.