Intensive neurorehabilitation and allogeneic stem cells transplantation in canine degenerative myelopathy

Débora Gouveia; Jéssica Correia; Ana Cardoso; Carla Carvalho; Ana Catarina Oliveira; António Almeida; Óscar Gamboa; Lénio Ribeiro; Mariana Branquinho; Ana Sousa; Bruna Lopes; Patrícia Sousa; Alícia Moreira; André Coelho; Alexandra Rêma; Rui Alvites; António Ferreira; Ana Colette Maurício; Ângela Martins

doi:10.3389/fvets.2023.1192744

Intensive neurorehabilitation and allogeneic stem cells transplantation in canine degenerative myelopathy

Front Vet Sci. 2023 Jul 13:10:1192744. doi: 10.3389/fvets.2023.1192744. eCollection 2023.

Authors

Débora Gouveia^{1

2

3}, Jéssica Correia^{1

3}, Ana Cardoso^{1

2}, Carla Carvalho¹, Ana Catarina Oliveira^{1

2}, António Almeida⁴, Óscar Gamboa⁴, Lénio Ribeiro³, Mariana Branquinho^{5

6

7}, Ana Sousa^{5

6

7}, Bruna Lopes^{5

6

7}, Patrícia Sousa^{5

6

7}, Alícia Moreira^{5

6

7}, André Coelho^{5

6

7}, Alexandra Rêma^{5

6

7}, Rui Alvites^{5

6

7

8}, António Ferreira^{4

7

9}, Ana Colette Maurício^{5

6

7}, Ângela Martins^{1

2

3}

Affiliations

¹ Arrábida Veterinary Hospital, Arrábida Animal Rehabilitation Center, Setubal, Portugal.
² Superior School of Health, Protection and Animal Welfare, Polytechnic Institute of Lusophony, Lisboa, Portugal.
³ Faculty of Veterinary Medicine, Lusófona University, Lisboa, Portugal.
⁴ Faculty of Veterinary Medicine, University of Lisbon, Lisboa, Portugal.
⁵ Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salaza, Universidade do Porto, Porto, Portugal.
⁶ Centro de Estudos de Ciência Animal, Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto, Porto, Portugal.
⁷ Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), Lisboa, Portugal.
⁸ Instituto Universitário de Ciências da Saúde (IUCS), Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Gandra, Portugal.
⁹ CIISA - Centro Interdisciplinar-Investigáo em Saúde Animal, Faculdade de Medicina Veterinária, Av. Universi dade Técnica de Lisboa, Lisboa, Portugal.

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.

Keywords: degenerative myelopathy; dogs; electrical stimulation; intensive neurorehabilitation; locomotor training; mesenchymal stem cells.

Grants and funding

RA acknowledges the Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA), Porto University (UP), and Fundação para a Ciência e Tecnologia (FCT) for the funding and availability of all technical, structural, and human resources necessary for the development of this study. This study was supported through the project UIDB/00211/2020 funded by FCT/MCTES through national funds. The authors acknowledge FCT for funding the project 2022.04501.PTDC (Olfabionerve—Olfactory Mucosa Mesenchymal Stem Cells and Biomaterials Promoting Peripheral Nerve Regeneration) and the PhD Scholarships AS (SFRH/BD/146689/2019) BL (2021.05265.BD). PS acknowledges Instituto Politécnico de Leiria—Center for Rapid and Sustainable Product Development (CDRSP), University of Porto (UP), Centro de Estudos de Ciência Animal (CECA), and Instituto de Ciências, Tecnologias e Agroambiente (ICETA) for the funding (UIDB/04044/2020) and availability of all resources needed for this study. Amo acknowledges the project H2Cure—Desenvolvimento de formulações de géis e pensos de Mel, Goma Gelana e Ácido Hialurónico para tratamento de feridas—POCI-01-0247-FEDER-047032 for financial support. Aco acknowledges the project PRECOGFIL—Filamentos dentados pre-tensionados para correção transvaginal do prolapso do compartimento anterior e posterior—PTDC/EMD-EMD/2229/2020 for financial support.