Gait challenges in Parkinson's: new research directions

Summary statement

Gait dysfunction is a common symptom of Parkinson’s and is often one of the more distressing symptoms for people to experience. Causing difficulties with walking such as falling, freezing, and shuffling steps, gait dysfunction tends to slowly get worse as Parkinson’s progresses. Unfortunately, research into gait dysfunction has also been traditionally difficult, but recent work has been investigating the underlying pathobiological mechanisms behind gait dysfunction and promoting unified research methods that will drive this work forward to better help people living with Parkinson’s. 

Article review 

When studying neurodegenerative conditions like Parkinson’s, one of the most important first steps toward developing treatments is fully understanding the pathobiological mechanisms underlying symptoms and how that progresses. Knowing which brain regions are most impacted by the condition or symptom in question, which cells are primarily affected, if there are specific cell processes that are mostly being interrupted, which genetic variations are driving this; knowing what is happening at a biological level gives you targets to interrupt the mechanisms of the condition. That’s the principle behind why levodopa is the first-line treatment for Parkinson’s. The primary biological cause behind Parkinson’s as a whole is dopamine neurons degenerating, so a treatment that helps improve levels of dopamine in the brain is the first-line approach to improve symptoms, even if just temporarily. 

The degeneration of dopamine neurons in the substantia nigra, a part of the midbrain heavily involved in motor control, is what is typically attributed to Parkinson’s. When the alpha-synuclein protein misfolds and accumulates in the brain, it interrupts cell and brain function and causes those neurons to degrade and die. However, there’s also evidence that alpha-synuclein aggregates can be found in other parts of the nervous system throughout the body, and that neural dysfunction is present in more ways than just the loss of neurons. 

To further understand the full breadth of Parkinson’s pathology and how it effects gait dysfunction specifically, researchers at the University of Toronto performed a comprehensive review of the scientific literature around the pathobiology of this symptom. Published in Trends in Neuroscience in March 2025, this paper breaks down where in the brain and the larger nervous system Parkinson’s pathology is located, how multiple different areas are implicated in gait dysfunction, and how this knowledge can be leveraged to help address gait dysfunction clinically. 

What the authors found in their review of the overall body of the literature suggests that, as Parkinson’s progresses, the pathological hallmarks appear to spread throughout the nervous system. When examining the brains of people who have experienced various severities of Parkinson’s, pathological alpha-synuclein clumps are found in the motor cortex of the brain, the basal ganglia and substantia nigra, and further down into the brainstem and spinal cord. The reason this is so important is that movement is a complex process, and there is no one brain area that controls it unilaterally. The severity of a motor symptom like freezing of gait appears to be driven in part by how widespread the pathology is and which areas of the brain and larger nervous system it is present in. 

With that in mind it helps explain why gait dysfunction can be so difficult to manage. With the symptom being a combination of processes happening biologically and differing from person to person, a treatment like deep brain stimulation targeting just one area of the brain may not be sufficiently effective, for example. The big question for future research and development of treatments then becomes how the field can more comprehensively understand the unique biological interconnectedness of gait dysfunction as a symptom and how each person’s presentation of the symptom is biologically different. It’s not enough to just understand that this is a problem, but to figure out how it can be addressed. 

The study authors discuss a few approaches for this. First is to work on better understanding the different neural pathways that are being impacted so that researchers know where to look when developing treatment approaches. Next, going along with that, is to improve imaging and biomarker development so that people can receive access to individualized care. For example, using MRI scans or looking for the presence of alpha-synuclein in cerebrospinal fluid can help clinicians pinpoint where the pathology is located in individual cases. The authors also discuss the use of electrodes and other brain activity trackers to help detect where in the neural pathway someone might be experiencing the most disruption, which would allow for treatments that target the areas of the brain further “up the chain” so to speak. 

Source: Cho, Kalia, & Kalia, 2025 

What is Parkinson Canada’s role? 

A committee was recently formed to consider this issue of gait dysfunction research and publish guidelines intended to help standardize gait dysfunction research measures. This committee, called the Gait Advisors Leading Outcomes for Parkinson’s (GALOP), was comprised of leaders in the field from many different organizations, including our Vice President of Research – Angelica Asis. 

Research into gait dysfunction has often used a variety of outcome measures and taken place in small studies that can make it difficult to scale up and apply in a more clinically meaningful way. That makes the important work of better understanding the pathobiology of the symptom that is required to improve treatments significantly more difficult and can slow down the overall pace of research. 

The GALOP committee made some important recommendations based on their own review of the literature and understanding of the Parkinson’s research infrastructure. One recommendation is for standardized research methods and measures to be applied to gait dysfunction research, so that findings are more broadly applicable and can be scaled up more easily for future research. Another recommendation is to apply standard metrics that have been validated for use in both early- and late-stage Parkinson’s, given the known difference in pathobiology and symptom progression that occurs over time. A third recommendation is to ensure that measures are used that include someone’s daily functioning and tracking of how their gait dysfunction is impacting their home life; this ensures that the research is being done in a way that’s relevant to someone’s daily well-being and isn’t just something useful in a lab setting that may not help someone in their day-to-day. 

Source: Mancini et al., 2025 – Figure 3 

Another major recommendation that the committee makes is to prioritize open science and collaboration between international researchers focused on Parkinson’s and gait dysfunction. Standardizing research methods internationally, merging datasets, and working collaboratively will help ultimately improve and speed up research. This committee was made up of a large number of Canadian representatives, including Ms. Asis, and we’re proud to be contributing on the global stage and advocating for people living with Parkinson’s. 

Ultimately, given the large negative impact of gait dysfunction on people’s well-being, it’s very important to better understand both the underlying biology driving this symptom, and how we can support better research to improve the development of treatments.