Total Investment – $100,000

Graduate Student Scholarship Program

Juan Jurado-Coronel, Western University

Oxidative stress-induced Nrf2 misfolding in Parkinson’s disease

Oxidative stress and aging are the primary risk factors for Parkinson’s disease (PD). The protein Nrf2 is particularly important in fighting oxidation and the associated damage in the brain as it activates antioxidant enzymes. Nrf2 is regulated by another protein called Keap1. These two proteins can get damaged under excessive oxidative stress conditions and thus contribute to neuronal death. In my study I will delve into how exactly Nrf2/Keap1 malfunction contributes to PD. I will study the different expression levels, localization, and activation of Nrf2/Keap1 in brain samples of PD patients using biochemical approaches and microscopy. Furthermore, by using well-established PD cell models co-expressing Nrf2/Keap1 with the PD-associated protein α-synuclein, we will study their interactions in PD. Cannabidiol (CBD), one of the main non-psychoactive molecules of Cannabis sativa, is a strong antioxidant that may mitigate the damage to Nrf2/Keap1, activate the Nrf2 pathway and thus slow down or even prevent neurodegeneration in PD. In sum, our study will elucidate the Nrf2 and Keap1 pathway in PD and assess CBD as a potential therapeutic for PD.

Mojtaba Sharafkha, Western University

Examining neural substrates of freezing of gait with structural MRI in patients with Parkinson’s disease

Parkinson’s disease (PD) is the second most common and fastest-growing neurodegenerative disease in the world. PD is characterized by both motor and non-motor symptoms. One significant motor symptom is freezing of gait (FOG), where patients experience sudden, involuntary interruptions in walking. FOG affects about 50% of PD patients, leading to falls and fractures. Unfortunately, there are no effective treatments for FOG, necessitating more research to understand its underlying mechanisms. Dopaminergic pathways, especially those involving the striatum—a part of the basal ganglia—and midbrain regions like the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), are crucial in the pathophysiology of FOG. Previous studies have shown MRI abnormalities in the striatum, VTA, and SNc in PD patients with FOG. However, these studies are limited in evaluating whole responsible brain regions in FOG versus specific subregions. The current study addresses this gap using advanced diffusion MRI (dMRI) techniques to examine specific subregions within the striatum and midbrain responsible regions between PD patients with and without FOG. Participants are recruited from the Parkinson’s Progression Markers Initiative (PPMI) database and categorized based on their FOG status (PD-FOG and PD-nonFOG). A novel parcellation technique is run on baseline MRI of all patients to evaluate the integrity of parcellated striatum, VTA/SNc compared to the integrity of the whole striatum, VTA/SNc between PD-FOG and PD-nonFOG patients. Focusing on subregions rather than whole regions, this study aims to uncover specific structural differences linked to FOG, potentially leading to objective prognostic MRI biomarkers and therapeutic targets for this debilitating symptom.

Nate Rothery, Western University

Developing a prognostic model for freezing of gait in Parkinson’s disease

This research project introduces a method to predict the onset of Freezing of Gait (FOG), a debilitating motor symptom in Parkinson’s Disease (PD), by leveraging Magnetic Resonance Imaging (MRI) and machine learning. FOG significantly reduces patients’ quality of life, and unlike other PD motor symptoms, FOG is notably resistant to treatment. Current therapeutic strategies are often ineffective because little is known about the underlying causes of FOG, and researchers are working on models to determine who is likely to develop FOG. Previous attempts at predicting FOG onset using neuroimaging alone have not been accurate enough for clinical use. To address this, our project focuses on analyzing changes in brain structure and connectivity, particularly in regions associated with motor, cognitive, and sensory functions, which are commonly disrupted in patients with FOG. By identifying these alterations, we aim to develop a robust predictive model for FOG onset. This research has the potential to transform clinical practice by enabling personalized medicine approaches and improving the selection process for clinical trials. Identifying patients at risk of developing FOG can enhance trial efficiency and reduce costs. Moreover, this research could pave the way for new therapies designed to prevent, delay, or modify the progression of FOG, ultimately improving outcomes for patients with PD.

Viveka Pimenta, Western University

Investigating Parkin Oxidation and its Impact on Parkinson’s Neurodegeneration

Parkinson’s disease (PD), a devastating neurodegenerative condition, is becoming increasingly prevalent in our aging population, yet the events leading to neuron death remain unclear. Current treatments aim to alleviate symptoms, but none address the cause of neurodegeneration, leaving a cure for PD elusive. Disease progression is marked by significant neuron loss in the brain region responsible for mobility, caused by oxidative damage to the neurons’ energy-producing mitochondria. During oxidative stress in PD, the enzyme parkin prevents cell death and neuron loss. However, the structure of parkin is inherently vulnerable to oxidation, and its protective role in PD requires recruitment to a highly oxidizing environment. The objective of this research is to determine the mechanism and consequences of parkin oxidation at the molecular and cellular levels. Understanding parkin oxidation in relation to its neuroprotective activity is essential for identifying the events that link oxidative stress to the death of motor neurons. This groundwork has the potential to advance the development of new and effective PD treatments aiming to slow neurodegeneration. In partnership with Parkinson Society Southwestern Ontario, this work aims to boost community awareness of scientific findings and provide an underserved population with educational resources to strengthen support systems.

Thank you to our Research Partners

Research fuels the journey toward a cure, bringing hope to those impacted by Parkinson’s. Parkinson Society Southwestern Ontario is proud to partner with Mitacs. Together, we’re advancing “Hope Through Research” and creating a brighter future for the Parkinson’s community.