Special Seminar: Exosomal miRNAs as biomarkers for neurodegenerative diseases

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by loss of motor neurons from the brain, brain stem, and spinal cord, resulting in progressive paralysis and death. Patients with frontotemporal dementia (FTD) usually present with either behavioural or language impairment secondary to atrophy of the frontal and/or temporal lobes. Recent evidence suggests that about 15% of patients with ALS develop FTD and about 15% of patients with FTD develop ALS. The overlap in clinical presentation and the recent discovery of shared genetic and pathological features have changed our view of ALS and FTD, which are now often thought of as diseases on a spectrum, rather than two distinct disease entities. There is increasing evidence that alterations in the expression of non-coding RNAs, such as microRNAs (miRNA or miR-), occur in ALS and FTD. In human biofluids, miRNAs have been found enriched in small vesicles termed exosomes, providing an opportunity for miRNA biomarker profiling. Studies presented here have identified dysregulated exosomal miR-204-5p and miR-632 in cerebrospinal fluid (CSF) as diagnostic biomarker candidates for genetic FTD and miR-632 also for sporadic FTD and ALS. MiR-204-5p was readily detected in neurons in brain and spinal cord tissue from patients and controls suggesting potential physiological roles in neurons and possibly a local source for this miRNA in the human CNS.

Biography:

Raphael Schneider's doctoral and postdoctoral research has primarily focused on biomarker discovery in neuroinflammatory and neurodegenerative diseases, with a particular interest in biomarkers that reflect underlying disease-mechanisms. After completing medical school in Germany, he dedicated three and a half years of postdoctoral research training to further develop his expertise in neuroimmunology at the Université de Montréal under the supervision of Dr. Nathalie Arbour. Following this scientific training, he continued his medical education with a 5-year residency in Adult Neurology at the University of Toronto. To further his understanding of the molecular mechanisms underlying neurodegeneration, he joined Dr. Janice Robertson's research group at the University of Toronto for his Ph.D., which he completed in early 2019. Dr. Schneider is currently a Neurologist at St. Michael's Hospital in Toronto. He believes that clinician-scientists are in a unique position to drive healthcare innovation and the translation of research into practice.