Grant: Doctoral: Vanier Canada Graduate Scholarships

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder characterised by motor neuron loss, muscle wasting, and weakness. Despite SMA being traditionally considered a motor neuron disorder, accumulating evidence suggests that non-neuronal cell types also contribute to the disease. Abnormalities in certain immune organs like the spleen and thymus have been observed in different SMA mouse models. However, it is currently unknown whether such deficits could make SMA patients more susceptible to disease due to impaired immunity, resulting in exacerbation of disease progression and impacting survival. Additionally, it could also result in neuroinflammation, which is a well-established contributor in many neurodegenerative disorders. Nonetheless, neuroinflammation has yet to be studied in SMA. Consequently, we hypothesize that altered immune function and neuroinflammation contribute to SMA disease pathogenesis. We aim to investigate immune function in SMA mice when challenged with various pathogens. We will also perform experiments to understand whether the immune defects are intrinsic or extrinsic. Next, we will investigate whether immune organs in SMA have toxic properties, especially by neuroinflammation. To extract relevance, we aim to confirm that immune organ defects are present in SMA patients. Understanding the functional consequences of immune organ dysfunction will offer guidance in the development of combinatorial therapies and thus highlight new important considerations to be taken in SMA patient care.