Andres Lozano, MD, PhD, FRCSC

University Health Network 

 Project name: Steps towards establishing low intensity transcranial ultrasound stimulation (TUS) of deep brain targets as a new therapy in Parkinson’s disease

Today, some patients with Parkinson’s disease (PD) may receive deep brain stimulation (DBS) to treat major motor symptoms. While DBS remains the gold standard for PD surgery, its invasiveness, complexity, and cost limit its accessibility and widespread deployment. Transcranial focused ultrasound (TUS) offers a potential non‑surgical alternative to DBS. Previous funding from the Weston Family Foundation enabled Dr. Lozano to test the application of TUS, demonstrating for the first time that low‑intensity TUS can directly modulate the activity of deep brain structures in patients with PD.

With support from the Follow‑on Funding program, Dr. Lozano and his team will determine the safe and optimal dose of TUS that can modulate the activity of deep brain regions that are primary targets for Parkinson’s disease, and evaluate its effectiveness in alleviating major motor symptoms, including tremor, rigidity, and bradykinesia. If successful, TUS could offer the therapeutic benefits of DBS through a non‑surgical, non‑invasive approach, with the potential to be transformative for patients living with PD.

Elizabeth Finger, MD, FRCPC, FAAN

Lawson Research Institute

Project name: A Randomized Double-Blind Placebo-Controlled Trial of Oxytocin and Goal Attainment Scaling for Apathy in FTD: Feasibility Pilot Study

Apathy is one of the most common symptoms of frontotemporal dementia (FTD), affecting approximately 80% of patients and consistently rated as highly burdensome by caregivers. Through a previous Weston Family Foundation grant, Dr. Finger conducted FOXY (Lancet Neurology), the largest positive clinical trial in FTD to date, which established the safe and optimal dose of intranasal oxytocin associated with improvements in apathy in FTD patients as reported by both care partners and clinicians. However, additional studies are needed to generate further supporting evidence to facilitate future uptake of this intervention into clinical practice.

With support from the Follow‑on Funding program, Dr. Finger and her team will evaluate the feasibility of a pragmatic trial design, intended to reduce geographic and other logistical barriers to participation, to inform a future Phase 3 trial assessing the real‑world effectiveness of oxytocin for apathy in FTD. If successful, this work will lay the foundation for the first effective pharmacologic treatment for apathy in FTD and, if confirmed in a future Phase 3 trial, has the potential to change clinical practice for this debilitating disease.

Paul Fraser, PhD

University of Toronto

Project name: IND-Enabling Studies for a SUMO-Based Therapeutic

Therapeutic strategies for Alzheimer’s disease (AD) have largely focused on enhancing amyloid clearance and reducing the production and/or aggregation of beta-amyloid. However, the severity of clinical dementia in AD patients is strongly correlated with synaptic changes, suggesting that therapies aimed at limiting synaptic loss may represent a promising approach to prevent cognitive decline. Small ubiquitin modifier (SUMO) proteins are an underexplored therapeutic target that could address this need given their role in synaptic biology.

Through a previous Weston Family Foundation grant, Dr. Fraser and his team developed a novel SUMO-based therapeutic, SBT02, which was shown to not only prevent, but also reverse, memory loss and impaired brain function in mouse models of AD. However, to advance SBT02 toward testing in patients, additional evidence is required to support regulatory approval by national health agencies.

For his current Follow-on Funding project, Dr. Fraser will conduct a comprehensive toxicological assessment to establish the safety profile of SBT02 and identify its underlying mechanism of action. If successful, Dr. Fraser’s work will provide information needed to progress SBT02 toward clinical trials, with the ultimate goal of developing a safe and effective treatment that preserves and potentially restores cognitive function in individuals with AD.  

Etienne de Villers-Sidani, MD FRCP(C) 

McGill University 

Project name: Development and validation of a digital biomarker-based tool for the early screening and monitoring of Alzheimer’s Disease 

Monitoring Alzheimer’s disease (AD) progression remains difficult because current assessments rely on lengthy, subjective, in-clinic interviews and cognitive tests. These tools are time-consuming, costly, and poorly suited for frequent monitoring or large-scale studies. Dr. de Villers-Sidani’s project addresses this challenge by developing and validating ETNA™-AD, a mobile, camera-based eye-tracking tool that provides objective estimates of cognitive function and disease severity. Running on an iPad Pro, ETNA™-AD guides patients through brief oculomotor tasks and uses machine-learning models to extract disease-relevant eye-movement signatures. Preliminary data in AD, as well as prior work in multiple sclerosis and Parkinson’s disease, show that these markers reliably reflect clinical scales such as CDR and MMSE. If successful, ETNA™-AD will deliver a fast, low-cost, and scalable method for tracking neurodegenerative disease progression. Its ability to generate standardized, quantitative endpoints remotely could transform clinical care, enable more inclusive monitoring, and accelerate therapeutic development for Alzheimer’s and related age-associated neurodegenerative disorders. 

Carmela Tartaglia, MD, FRCPC 

University Health Network 

Project name: Bringing precision medicine to neurodegenerative disease 

Patients with neurodegenerative diseases exhibit substantial molecular heterogeneity driven by distinct and often overlapping patterns of protein misfolding, aggregation, and spread. Co-occurring proteinopathies are the rule rather than the exception limiting the traditional one-size-fits-all therapeutic approaches. Although many treatments have targeted single pathologies, growing evidence indicates that this approach is often insufficient for meaningful disease modification. The field is therefore shifting toward precision medicine that aligns treatment with an individual’s molecular profile. Dr. Tartaglia proposes a precision medicine strategy using Seed Amplification Assays (SAAs), a sensitive and scalable method for detecting misfolded protein seeds from accessible biospecimens. Using SAAs as a high-throughput screen enables us to identify each patient’s unique combination of proteinopathies and use this molecular ‘fingerprint’ to guide patient-tailored therapeutic strategies. Such an approach would create a path toward a new framework for personalized drug discovery and therapeutic matching in neurodegenerative diseases. Instead of designing therapies around a singular, presumed driver of disease, treatment could be directed toward the actual co-pathologies identified in each individual. In turn, this may allow for simultaneous targeting of multiple proteinopathies, either through combination therapies, multi-target agents, or biologics designed to address specific misfolded species revealed by SAAs. 

Cheryl Wellington, PhD 

University of British Columbia 

Project name: Generation of Canadian reference intervals for plasma phosphorylated tau-217 

Dr. Wellington’s project aims to understand how the levels of an important blood biomarker called phosphorylated tau 217 (p-tau-217) could be the most promising diagnostic biomarker for Alzheimer’s disease (AD). In order to determine what an abnormal test result looks like, one first needs to understand what the normal levels are in the Canadian population. Dr. Wellington’s project will leverage a representative valid sample of Canadians to determine what normal levels of p-tau-217 are in the Canadian population. Her and her team will measure p-tau-217 levels in approximately 2500 samples, providing an unprecedented base of how p-tau-217 levels change during aging. P-tau-217 is the best plasma test to confirm a diagnosis of Alzheimer’s Disease and our study will help to launch p-tau-217 testing in Canada. In addition to clinical application in confirming an AD diagnosis and establishing eligibility to receive Lecanemab, our study will also serve as a foundation of knowledge for many more research studies on whether p-tau-217 can be used to determine how quickly a patient will progress, whether common comorbidities of aging such as cardiovascular disease affect p-tau-217 levels, and many other questions.  

Stuart Fogel, PhD 

University of Ottawa 

Project name: Targeted enhancement of sleep to restore sleep-dependent memory consolidation in prodromal dementia  

Changes in sleep are the earliest indicator of age-related cognitive decline and have been identified as one of the best potential modifiable and yet-to-be-exploited targets for prevention of dementia. Dr. Fogel’s previous work has identified potential, yet unexplored, therapeutic targets during sleep. He and his team will enhance sleep by targeting these markers using natural health products, with the aim of restoring the boost that sleep affords to memory processing. If successful, this research will provide proof-of-concept for the use of therapeutics to restore the benefit of sleep for memory and cognition at the earliest stages of cognitive decline. This will lead to the development of targeted interventions during sleep meant to alter the trajectory of age-related cognitive decline that occur in neurodegenerative diseases of aging. 

Philippe Huot, MD, PhD

McGill University

Project name: Characterization of novel GlyT1 inhibitors for the treatment of Parkinson’s disease 

Parkinson’s disease is characterized by motor symptoms such as tremor, stiffness and slowness of movement. Levodopa is the most effective treatment for Parkinson’s disease, but its use is often complicated by the occurrence of uncontrollable abnormal involuntary movements, referred to as dyskinesia, as well as a shorter duration of symptom relief, referred to as fluctuations. In experimental models of Parkinson’s disease, we have discovered that increasing the levels of the amino acid glycine in the brain diminishes the severity of dyskinesia. However, most glycine-enhancing drugs face hurdles that prevent their development for the treatment of Parkinson’s disease. In this project, Dr. Huot proposes to determine the effect of novel glycine enhancers on the severity of dyskinesia and motor symptoms, in an experimental model of Parkinson’s disease. He and his team will also determine what concentrations of the drug in the blood are associated with a reduction of dyskinesia and improvement of motor symptoms. Together, this data will inform what doses should be investigated in future clinical trials of patients with Parkinson’s disease. 

Amanpreet Badhwar, PhD 

Research Centre of the Institut universitaire de gériatrie de Montréal (CRIUGM) 

Project name: Translational Integration of Blood-Based Biomarkers and Virtual Reality Cognitive Testing for Enhanced Subtyping of Subjective Cognitive Decline 

As people age, many begin to notice subtle memory changes. When these concerns occur but standard memory tests still look “normal,” the condition is called Subjective Cognitive Decline (SCD). Although often overlooked in the clinic, SCD can be an early warning sign for future memory problems, including mild cognitive impairment or dementia. Unfortunately, today’s tools are not sensitive enough to identify who is truly at risk. Dr. Badhwar’s project aims to change that by developing a more accurate way to assess early cognitive decline. Her and her team will combine two innovative approaches: a virtual-reality (VR) memory test that can detect subtle changes in how people remember and organize information; and a blood test measuring a panel of 30 proteins linked in previous studies to early changes in the brain before overt symptoms of dementia appear. Dr. Badhwar and her team will then use machine learning to see which combination of VR performance and blood proteins best predicts who has more significant memory concerns and who will be most likely to progress to mild cognitive impairment in years to come. By developing a sensitive and scalable assessment tool, this project aims to improve early detection and help identify individuals who may benefit most from early intervention or monitoring. 

Peter St George-Hyslop, MD 

University of Toronto 

Project name: Antisense oligonucleotide-mediated therapeutic knockdown of the ABI3 Alzheimer risk gene 

Alzheimer’s disease (AD) remains a major cause of dementia worldwide, driven by accumulation of misfolded proteins and chronic neuroinflammation. As the pathology advances, resident immune cells of the brain, microglia, which mediate the clearance of toxic misfolded protein deposits, become dysfunctional. Existing anti-amyloid therapies provide only modest benefit, underscoring the need for novel approaches targeting other aspects of the disease such as microglial dysfunction. Dr. St George-Hyslop’s project targets ABI3, an AD-associated microglial protein implicated in immune cell functions. Genetic studies in AD mouse models show that loss of ABI3 markedly enhances microglial phagocytosis of amyloid and attenuates disease progression without detectable adverse effects. Building on these findings, the project will use antisense oligonucleotides (ASOs) as a clinically validated gene-modulating approach to selectively reduce ABI3 expression in microglia. The work will define the safety profile, optimal dosing parameters, and therapeutic window of ABI3-ASO treatment in vivo before and after onset of pathology. If successful, this program will establish proof-of-concept for ABI3-directed microglial modulation as a disease-modifying strategy. Enhancing microglial function has the potential to slow down or prevent AD progression and could extend to other neurodegenerative diseases of aging in which innate immunity plays a central mechanistic role.