Alpha-synuclein plays a key role in the pathophysiology of Parkinson's disease, and researchers have been investigating this protein as a therapeutic target and also as a potential biomarker for the disease. The alpha-synuclein seed amplification assay, developed by Dr. Claudio Soto and colleagues, leverages the self-replicating nature of the misfolded alpha-synuclein proteins that form aggregates in Parkinson's disease. Amplifying misfolded alpha-synuclein can allow researchers and...

To help meet the growing global need for more movement disorders specialists, The Michael J. Fox Foundation created the Edmond J. Safra Fellowship in Movement Disorders in collaboration with longtime partner the Edmond J. Safra Foundation. This program supports the training of movement disorders specialists who will provide expert care and drive advances in Parkinson's research. The program is positively impacting early-career clinician-researchers, as well as the centers where they train....

Stem cell models derived from patients with Parkinson’s disease are valuable tools that are helping researchers around the world to better understand the underlying causes of neurodegeneration and to develop biomarkers and new therapies. To maximize the potential impacts of these tools, it is critical that they are developed and shared according to the principles of open science. In her interview, Dr. Birgitt Schüle discusses her work developing alpha-synuclein cell lines, challenges and...

New qualitative and quantitative tools are being developed to measure and track changes in proteins relevant for neurodegenerative disease, and these tools have the potential to accelerate drug discovery and clinical trials. In this episode, Dr. Judith Steen discusses her work creating novel qualitative and quantitative tools and workflows at the interface of proteomics and transcriptomics, including their novel FLEXI platform. This platform uses targeted, high- throughput quantitative mass...

Substantial research has focused on identifying biomarkers for the diagnosis of Parkinson's disease (PD) as well as monitoring progression of the disease. In developing these biomarkers, it is critical for scientists to consider how the biomarkers will ultimately be used in the clinic and in clinical trials research. In this interview, Dr. Charles (Chuck) Adler shares his perspectives on how biomarkers are currently being used in clinical and research contexts, and what it would take for him...

Sleep disturbances, such as insomnia, sleep fragmentation, excessive daytime sleepiness, and REM sleep behavior disorder are common in people with Parkinson's disease (PD). Poor sleep quality can also impact other domains of function, including motor function. Prior research has shown that a type of photoreceptor cell in the retina, called melanopsin cells, provide the main light signals to the brain to initiate sleep, and function of these cells is impaired in PD. Dr. Beatix Feigl and her...

Though existing evidence supports that dysfunction in the clearing of cellular debris plays an important role in the development of Parkinson's disease, many unanswered questions remain regarding the mechanisms of the autophagy-lysosomal pathway involved in this process. In particular, research in the field has been limited by a lack of reliable, quantitative tests for monitoring autophagy-lysosome activity. In this interview, Dr. Zhenyu Yue describes his research investigating the cellular...

Evidence supports that dysfunction in the homeostasis of iron and other elements likely contributes to the pathophysiological mechanisms of Parkinson's disease, but we have yet to develop suitable elemental biomarkers for use in diagnosing and monitoring the progression of Parkinson's disease. Dr. Paul Lingor discusses his work in this area to identify patterns of bioelements in CSF that could serve as PD biomarkers. Beyond CSF, he is also examining tear fluid as a potential biomarker source...

Identifying reliable biomarkers for the diagnosis and prognosis of Parkinson's disease and atypical parkinsonism would have substantial impacts on clinical trials and clinical practice. A particularly active area of research is the development of novel molecular imaging biomarkers that can be used in combination with common neuroimaging approaches. Dr. Antonio Strafella discusses current practices for using molecular imaging biomarkers in research and in the clinic, the process of developing...

Prior studies have established links between poor olfaction and Parkinson's disease, and impaired sense of smell is a common prodromal symptom of Parkinson's disease. The causes and mechanisms of prodromal neurodegeneration are actively being researched. However, environmental exposure to pesticides or other chemicals may trigger or modify the course of neurodegeneration, potentially leading to the development of Parkinson's disease over time. In this episode, Dr. Honglei Chen shares his...

Gait impairments such as slow speed, small steps, and high variability from step to step are common in people with Parkinson's disease, and these changes begin to occur early in the course of disease. Freezing of gait may develop later for some individuals, and it has been linked to falls and other adverse outcomes. When the quality of walking declines, it can lead to a reduction in the quantity of walking and overall physical activity, which is also related to poorer health outcomes. To...

Improving our understanding of the complex neural circuits involved in normal function of the basal ganglia and other parts of the brain impacted by Parkinson's disease is critical for developing more targeted and more effective treatment approaches. In this episode, Dr. Aryn Gittis discusses her research examining how the activity of specific basal ganglia circuits relates to motor control in both health and pre-clinical models of movement disorders like Parkinson's disease. She describes...

Demand for movement disorder specialists continues to grow, but not enough neurologists are receiving focused training in Parkinson’s and related conditions in order to meet the current and projected needs in the U.S. and around the world. In collaboration with longtime partner the Edmond J. Safra Foundation, The Michael J. Fox Foundation created the Edmond J. Safra Fellowship in Movement Disorders with the goal of growing the global base of movement disorders specialists. In this episode Dr....

Trichloroethylene (TCE) and related chemicals like perchloroethylene (PCE) have been used widely for a variety of commercial purposes over the past century, and these chemicals are prevalent in the air, water, and soil. Over the past several decades, mounting evidence has been published linking exposure to TCE/PCE with adverse health effects, including cancer and Parkinson's disease. In this episode, Dr. Sam Goldman discusses his research on environmental risk factors for Parkinson’s disease,...

For over a century, different surgical interventions have been explored to address symptoms of Parkinson's disease, and researchers are continuing to innovate and improve surgical treatments today. With new technology and an ever-expanding understanding of the function of the nervous system and the pathophysiology of Parkinson's disease, neurosurgical interventions are becoming more effective and more personalized. Dr. Doris Wang joins us in this episode to discuss her work using focused...

The Michael J. Fox Foundation for Parkinson's Research established its Research Tools Program to address gaps in the field and common challenges surrounding the development of reagents and models that slowed the initial stages of promising research projects. In collaboration with many partners and stakeholders, the Research Tools Program helps ensure that scientists around the world have access to high-quality reagents, models, and more. These tools have been instrumental in launching novel...

Increasing evidence supports the presence of sex and gender differences in neurodegenerative conditions, including Alzheimer's disease and Parkinson's disease. There is a critical need to more closely examine sex and gender differences in all stages of research, therapeutic development, and clinical treatment to enable better outcomes through precision medicine approaches. This episode focuses on the relevance of sex and gender factors in Parkinson's disease and efforts to transform...

Atypical Parkinsonian Syndromes, such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and dementia with Lewy bodies are often initially diagnosed as Parkinson's disease. Incorrect, incomplete, or delayed diagnoses are barriers to beginning the most appropriate treatment early in the disease course. More research is needed to facilitate early diagnoses, understanding of disease pathogenesis, and monitoring of disease progression....

For many years, Parkinson's disease and dementia with Lewy bodies have been defined using clinical features. With recent advances in biomarkers, particularly the alpha-synuclein seed amplification assay that allows us to detect misfolded and aggregated alpha-synuclein in cerebrospinal fluid, it is now possible to identify the presence of pathological neuronal alpha-synuclein in living patients. With input from diverse stakeholders, a new biological definition of neuronal alpha-synuclein...

There is a pressing need to develop safe and effective disease-modifying and symptomatic treatments for Parkinson's disease. Through improvements in our understanding of the pathophysiology of the disease, as well as genetic risk factors, new potential treatment targets have emerged. However, bringing a promising new compound from the lab through all of the steps of drug development is a long, difficult, and resource-intensive process. In recent years, collaborative efforts and advances in...

In neurodegenerative conditions such as Parkinson's disease (PD), patients often do not receive a diagnosis until the hallmark motor symptoms begin to manifest. This can be a decade or more after substantial changes start occurring in the brain. A major goal of the PD research field has been to develop methods for earlier detection and intervention. Over the years, there have been substantial advances in neuroimaging techniques and biological biomarkers that have allowed us to more accurately...

A substantial portion of people with Parkinson's disease (PD) have a family history of the disease, and new findings continue to improve our understanding of relevant genetic variants. These discoveries are key for clarifying the mechanisms that lead to Parkinson's disease as well as the development of new therapies. The Global Parkinson's Genetics Program (GP2) was established to gather and integrate genetic and clinical data from diverse participants around the world to expand our knowledge...

A growing body of evidence is expanding our understanding of the links between inflammation, our immune responses, brain health, and neurodegeneration. In particular, several genes associated with Parkinson's (including LRRK2) are known to be involved in inflammation, and peripheral inflammation has been shown to influence brain function and contribute to the development of neurodegenerative diseases. Better understanding the roles of inflammation and our immune responses in Parkinson's...

Mutations in the LRRK2 gene were first linked to Parkinson's disease (PD) risk in 2004. Since then, researchers from around the world have advanced our understanding of the mechanisms through which LRRK2 may contribute to PD, leading to the development of three potential LRRK2-targeted therapies that are now being evaluated in clinical trials. Along with colleagues and collaborators, Dr. Dario Alessi has pioneered new research and approaches that have aided in the development of drugs to...