Unity Walk > American Parkinson Disease Research Grants 2018

 

American Parkinson Disease Association is using its 2018 distribution to fund:

Diversity in Biomarker Discovery

Protective role of the oral microbiome in Parkinson’s disease

Menopause as an important transition state in the susceptibility to Parkinson’s disease (PD)

 

PROJECT TITLE:  Diversity in Biomarker Discovery

Investigator/Author:  Elizabeth Disbrow, PhD

Objective:  The goal is to identify a brain imaging biomarker of disease severity that is applicable to a diverse sample of people with PD. 

Background:  Existing studies suggest that there are racial differences in the incidence and progression of PD. While the incidence of PD appears to be lower in the black compared to white population, progression may be steeper.  However, data from the African American population is sparse.    Recently we identified imaging markers of disease subgroups that were associated with rate of disease progression based on brain imaging markers of neuronal integrity in early stage PD.  We will extend this work to examine differences in disease severity across racial groups.

Methods/Design:  We will collect MRI, motor, cognitive and comorbidity data from black and white PD and control participants.  We will look at particular MRI features and examine the relationship  between imaging data and  clinical measures of disease severity across racial groups.

Relevance to Diagnosis/Treatment of Parkinson’s Disease: The development of biomarkers of PD disease state and progression may provide mechanistic insight and hopefully accelerate the development of disease modifying therapies. 

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PROJECT TITLE:  Protective role of the oral microbiome in Parkinson’s disease

Investigators/Authors:  Cameron Jeter, PhD

Objectives: Our study will determine how changes in oral bacteria are associated with the onset and progression of dysphagia (difficulty swallowing) and the risk of aspiration pneumonia in patients with PD.

Background: Difficulty swallowing, or dysphagia, affects up to 80% of patients with PD, leading to malnutrition, dehydration and aspiration, a process by which contents in the mouth enter the lungs due to a poor swallow. Dysphagia leads to changes in diet and in oral movements, that then can alter the composition of the oral bacteria. Changes in oral bacteria in turn, can affect the risk of whether an aspiration event causes pneumonia, as particular bacteria are more likely to cause pneumonia than others.

Methods/Design: We will take samples of oral bacteria from patients who have had PD for 10 years or longer and track the severity and progression of their dysphagia and oral microbiome for several years.  This will allow us to determine if dysphagia alters the oral bacteria, and what species are associated with high or low risk of aspiration complications.

Relevance to Diagnosis/Treatment of PD: By understanding how the makeup of oral bacteria of patients with PD changes with onset of dysphagia, we may be able to eventually use oral bacteria composition as a biomarker for dysphagia.  Importantly, future studies may determine how dietary and oral care recommendations or oral liquid probiotics can be used as non-invasive therapies to improve the quality and duration of life of patients with PD

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 PROJECT TITLE:  Menopause as an important transition state in the susceptibility to Parkinson’s disease (PD)

Investigators/Authors:  Roberta Marongiu, PhD

Objectives: The goal is to characterize the influence of the estrogen decline during menopause on susceptibility to PD in a mouse model overexpressing alpha-synuclein (αsyn).

Background:
 Pre-menopausal women have about a 2-fold reduced risk of developing PD as compared to men and post-menopausal women, suggesting that estrogen plays an important role in protecting against PD. Early menopause, either natural or surgical, is associated with an increased risk of PD. Menopausal women who had received estrogen are less likely to develop PD than those who had not. However, the mechanisms underlying the protective role of estrogen against PD progression remain unclear.  We hypothesize that loss of estrogen during menopause will decrease the neuroprotective advantage observed in young female mice, accelerating the appearance and progression of PD in our mouse model.

Methods/Design:  We will use a mouse model of PD which was engineered to contain human αsyn and which demonstrates αsyn pathology in the brain, resultant nerve degeneration, and motor impairment. In this model, we will characterize the influence of inducing menopause on PD pathology and motor deficits.

Relevance to Diagnosis/Treatment of PD:
The proposed work will help to clarify the ways in which estrogen influences PD progression. A better understanding of the underlying molecular mechanisms can lead to the development of novel targeted treatments for PD.

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