Canine degenerative myelopathy (DM) is an adult onset progressive neurodegenerative disease in dogs that shares many characteristics with inherited amyotrophic lateral sclerosis (ALS) in humans. ALS triggers a deterioration of the nerves that connect the brain to the muscles, leading to stiffness, slowing of movement, loss of muscle tissue and weakness. Dogs with DM initially develop incoordination and progressive weakness of their rear legs resulting in paralysis within one year from onset of signs. We believe that naturally-occurring canine DM will provide a useful disease model for ALS therapy development because dogs with DM have clinical signs that are similar to human ALS symptoms. 

The immune system, specifically microglia, the primary immune cells of the central nervous system (CNS), has been implicated in ALS disease progression. The rodent models have shown that microglial cells, which normally provide an immune defense for the central nervous system, become abnormally activated in ALS to produce neurotoxicity. Therapeutics targeting microglia have slowed disease progression in rodent models, but have failed to translate into effective therapy for ALS patients.

The focus of Dr. Sibigtroth’s research is to characterize the role of microglia in DM progression. This study will examine the hypothesis that the normal communication between motor neurons and microglia is disrupted in DM, inducing a behavioral change in microglia cells. Microglia will transition from a neuroprotective to neurotoxic behavior, leading to progressive motor neuron damage and dysfunction. Owners of companion dogs with DM tend to have their pets euthanized at different stages of disease severity and examination of the donated tissues from these dogs will provide an effective way to study the various stages of DM progression. This work will provide valuable insight into the role of microglia within canine DM disease progression and could identify key areas for the development of microglia-specific therapeutic targets that could slow or halt further disease progression.

The AGSDCF is proud to announce that it is the sole sponsor of this important fellowship.

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