Unity Walk > Parkinson's Foundation Research Grants 2018

 

 

Parkinson's Foundation is using its 2018 distribution to fund:

A specific and less toxic alpha-synuclein strain is a possible progression biomarker for Parkinson’s Disease-related cognitive impairment

Brain mechanisms underlying response to visual cues for gait impairment in Parkinson’s disease

 

PROJECT TITLE:  A specific and less toxic alpha-synuclein strain is a possible progression biomarker for Parkinson’s Disease-related cognitive impairment

Investigators/Authors:  Liana Rosenthal, M.D.; Johns Hopkins University

Objective: The purpose of this study is to determine whether a specific, less toxic strain of alpha-synuclein is a potential progression marker of Parkinson’s disease (PD)-related cognitive impairment.

Background: Alpha-synuclein directly relates to the pathophysiology of PD and is therefore a potential biomarker. Previous investigation into alpha-synuclein as a biomarker for PD, however, has fallen short. Previous studies have looked at the concentration of alpha-synuclein in the CSF, but this is not a reliable marker for PD progression or diagnosis. Other changes to alpha-synuclein have been measured in PD patients vs. healthy subjects, but none of these potential biomarkers have held up as tests that we can use in clinic or research. This investigation recognizes the importance alpha-synuclein while taking a different approach. We will examine the folding structure of alpha-synuclein to determine if a specific, less toxic strain is a potential biomarker for PD.

Methods/Design: Using cerebrospinal fluid (CSF) samples from the Johns Hopkins Parkinson’s Disease Biomarker Program (JHU PDBP) and the Pacific Udall—Seattle cohort, we will amplify the concentration of misfolded alpha-synuclein using the protein misfolding cyclic amplification (PMCA) technique that is similar to PCR for DNA. We will then be able to evaluate differences in protein folding and toxicity and compare alpha-synuclein strain to clinical outcome. We will first test the alpha-synuclein strains among the existing baseline CSF to determine the prevalence of this less toxic strain among individuals who have normal cognition. We will also extend the follow up time of the JHU PDBP through a single telemedicine-based visit, allowing us to determine if this alpha-synuclein strain is predictive of a slower disease course.

Relevance to Diagnosis/Treatment of Parkinson’s disease: The dementia that many individuals with Parkinson’s disease (PD) develop is devastating to both patients and their families and is associated with significant increases in morbidity and mortality above individuals with PD alone. There are currently no tests to determine which patient’s will develop dementia and/or how quickly they will do so. By identifying progression markers for PD related dementia, we will have the potential to improve the function, health, and mortality of individuals with PD.

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PROJECT TITLE:  Brain mechanisms underlying response to visual cues for gait impairment in Parkinson’s disease

Investigators/Authors:  Samuel Stuart, PhD; mentor: Martina Mancini, PhD., Oregon Health and Science University

Objective: The two goals of this study are to understand brain activity in response to visual cues when walking in PD, and to investigate the relationships between attention, brain activity, and gait responses to visual cues in PD.

Background: Walking impairments are common in PD and lead to increased falls risk, as well as reduced mobility and quality of life. Impairments include reduced speed and step length. Freezing of gait (FoG) is one of the most debilitating deficits in PD, which is defined as “a brief absence or reduction of walking despite the intention to continue” and patients describe this as a feeling of their feet being stuck to the floor. Walking impairments are difficult to treat, due to the lack of response to anti-Parkinsonian medications. Therapeutic interventions, such as visual cues (transverse lines on the floor to step over) are often used to overcome walking impairments, but the reasons for their beneficial effect are unknown. This has led to not all patients not benefiting, as well as only short-term benefit to a few impairments (e.g. step length). For people with PD, being able to use specific brain regions to pay attention to the visual cues to focus on each step has been suggested as the reason they are able to overcome their walking deficits, but this has not been tested.

Methods/Design: This study will use non-invasive inertial sensors and electroencephalography (EEG) during walking with and without visual cues in PD (we will be testing patients that experience FoG vs. patients that do not) to monitor gait and brain region response to cues. EEG measures the electrical activity of the brain, with greater electrical signal representing increased brain activity. We believe that visual cue response relies on the ability to increase brain activity in attention-related brain regions, which will be most required in those who experience FoG.

Relevance to Diagnosis/Treatment of Parkinson’s disease: Understanding the reasons why walking improves with visual cues is vital to improve their use and to develop more effective, targeted treatments for individuals.

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