Canine degenerative myelopathy: latest updates and preliminary results of mesenchymal stem cells treatment

Abstract

Canine Degenerative Myelopathy (DM) is a neurodegenerative disorder affecting dogs in late adulthood. The clinical picture typically starts as a slowly progressive and unpainful T3 to L3 myelopathy. Then, the clinical spectrum progresses to a Lower Motor Neuron flaccid paraplegia and it gradually ascends to affect the thoracic limbs causing tetraplegia. In the last stage bulbar signs occur and, if euthanasia is not performed, DM-affected dogs die from respiratory failure. The prevalence for DM among the population is 0.19%. Large breeds are more represented than small breeds (Coates and Wininger, 2010). According to the literature, the main risk factors for developing the disease are the breed and homozygosity for SOD1:c.118G > A. Since the discovery of the SOD1 mutation in the majority of DM affected dogs, DM has been considered a natural occurring model for Amyotrophic Lateral Sclerosis (ALS) (Awano et al., 2009). Similarities between these two disorders include genetic basis, clinical hallmarks and histopathological features. Unfortunately, they also share the lack of an effective therapy. Therefore, their prognosis remains poor. Over the last years, an increasing number of studies on both SOD1 transgenic mice and humans has evaluated that Mesenchymal Stem Cells (MSC) therapy is a promising treatment for ALS based on its neuroprotective effects. In addition, biomarkers for DM are still not available in clinical practice, though they could be an instrument to obtain an earlier diagnosis and to objectively monitor the disease. This thesis has three objectives. In the first place, it evaluates the signalment and history of the 12 DM-affected dogs which were referred to the veterinary teaching hospital of Parma University (OVUD) between February 2019 and March 2022. Among these dogs, weight over 25 kg was found to be predominant in DM affected dogs and it was also correlated to earlier onset of symptoms. Further investigation with a larger sample is needed to assess whether weight could be a risk factor for developing DM. In the second place, the thesis describes the preparation of MSCs from adipose tissue and the intravenous and intrathecal administration for the therapy of DM in two dogs which were referred to OVUD between 1st May 2021 and 31st March 2022. Finally, samples of Cerebrospinal Fluid (CSF) and serum has been collected to evaluate phosphorylated neurofilament heavy (pNF-H) levels as a potential marker of DM. As pNF-H values will be available, they will be compared to other sample from dogs without neurological disorders.