Funding from The Parkinson Alliance helped to finance the following Parkinson’s research. Grantees were selected by scientific review committees of participating organizations. Updates will be posted, when available.
Project Title: Exploring the Influence of the Gut Microbiome in Parkinson’s Disease
Principal Investigator(s): Beate Ritz
Objective/Rationale: Evidence is mounting that human microbiome can affect aspects of neurologic function, brain activity, and behavior via the ‘gut-brain-axis’; importantly, it may also play an important role in the progression and the onset of Parkinson’s disease (PD). Constipation, loss of smell and sleep disturbances can occur as early as 20-30 years prior to PD diagnosis and affect as many as 80% of patients. Nevertheless, the role of the gut microbiome in PD is still underexplored.
Project Description/Methods/Design: We plan to capitalize on patient resources from a previous case-control study of PD (Parkinson’s Disease Susceptibility Genes and Pesticides Study (PEG)), and for the first time join forces with Drs. Mayer and Jacob (UCLA Gastroenterology) – experts in brain-gut connection microbiome research – to generate pilot data in support of a new grant that will explore novel GI hypotheses for PD etiology and progression. We propose to collect fecal samples to analyze the bacterial gut flora of 70 PEG study PD patients and 50-70 matched controls (25 household & 25 community controls) and employ 16S ribosomal RNA (genetic identification of gut bacteria) to assess microbiome differences while controlling for a number of co-variates including diet and sex. Specifically, our hypothesis is that we will find some compositional and functional differences in patients vs. controls.
Relevance to Treatment of Parkinson’s Disease: This is the first time that we will venture into this new and expanding field of GI contributions to PD onset and progression. We hope that what we learn from this project will help inform future treatments of pervasive GI problems in PD as well as suggest some interventions that contribute to improved health-related quality of life in PD overall.
Expected Outcome: We expect that our research may contribute to the discovery of potentially novel etiologies and treatment options in PD and to be able to address hypotheses about the contributions of diet, environmental factors, and disease status to microbiome composition and to GI tract problems in PD.
Project Title: The Walk-Safe Navigator (WSN): An Advanced Wearable for Fall Avoidance in Parkinson’s Disease
Principal Investigator(s): John-Ross Rizzo, MD, MSCI
Objective/Rationale: Parkinson’s disease (PD) is a disorder of chronic neurodegeneration that causes significant disability and reduces quality of life. PD precipitates not only motor impairment but also sensorimotor malfunction. PD patients often exhibit severe visual dysfunction in the absence of cognitive impairment. Visuospatial disturbances relevant to orientation are among the most troubling problems. It affects complex visual function and can manifest in many ways, such as difficulty in judging verticals, estimating the position of body parts, carrying out route-walking, and even visually scanning environments. In addition, Parkinson’s disease disturbs the understanding of motor and perceptual task timing, i.e., the ability to temporally process sensory information. Visual perception problems are believed to cause difficulty in tracking fast moving targets, as exploring and judging spatially relevant environmental cues is impaired and therefore hinders the ability to pair motor activity (human response). Links between visual dysfunction and falls are ever-present, but, in Parkinson’s disease, when compounded by mobility limitations secondary to motor impairment, the situation becomes dire. We aim to address this critical need by leveraging advanced wearable technologies that autonomously map a user’s ambient environment and synthetically augment a PD end user with pertinent hazard information, maximizing safety and mitigating fall risk.
Project Description/Methods/Design: This proposal builds upon our expertise in assistive technologies (ATs), which represent a therapeutic alternative that focuses on task enablement and performance while driving towards decreases in falls, morbidity, and mortality. Over the last decade, we have built a multitude of advanced wearables (instrumented clothing and bags) that improve mobility while affording augmented safety and protection for individuals with a host of visual deficits. These devices are easily donned and doffed and look similar to conventional, commercially available products (vests/back packs). The key is seamlessly embedded sensors that extract pertinent information about obstacles and the environment and miniaturized, integrated (hidden) computer-controllers. These components are paired with ergonomic feedback systems, a low-profile haptic interface (belt), which communicates simple touch codes to users, and a headset, containing both speakers and a microphone.
We propose here to design, build, test and implement a specific wearable with a feature set called Curb Detector (WSN-CD). WSN-CD enables Parkinson’s Disease patients to more successfully navigate city streets and avoid overwhelming sensory information by adequately anticipating changes in elevation near intersections and curb transitions for sidewalk/roadway travel. We intend to improve safe and mitigate fall risk by squarely addressing previously characterized visual deficits, such as judging verticals and route planning. Our platform will automatically detect these curb borders, as would be encountered during travel, and label these relevant spatial markers relative to an end user. The information will be provided in the form of an auditory cue and/or touch cue, e.g., “alert- curb ahead, 10 feet out.” The end user will then able to better understand the spatial context of the local environment and more appropriately scan, anticipate and plan their next travel moves, improving safe way finding and most importantly avoiding falls.
Relevance to Treatment of Parkinson’s Disease: Unanticipated environmental features, such as curb transitions and drop-offs, turn hazardous when not attended to appropriately, undoubtedly precipitating mechanical trips and leading to unintended falls and grave injuries in the setting of Parkinson’s disease. Wearable-based, automated environmental monitoring and spatial cueing to relevant landmarks are robust approaches to mitigate risk in Parkinson’s disease.
Expected Outcome: We anticipate that navigation efficiency will significantly improve for those who travel with the advanced wearable, as compared to those who travel without. Navigation efficiency will be defined as a combination of walking speed, path length, and successful obstacle negotiation (avoiding dangers, e.g., curb drop-offs or sudden ground-elevation changes). Furthermore, and more globally, we expect to demonstrate the feasibility of mobile platforms capable of real-time scene understanding and action planning, representing the first of a series of novel research approaches in Parkinson’s.
Project Title: Registry for the Advancement of DBS in Parkinson’s Disease (RAD-PD)
Investigator/Author: Joohi Jimenez-Shahed, MD and Jim McInerney, MD
Objective: This project will identify the best practices surrounding DBS therapy, identify the adverse effects (and determinants) of DBS therapy, and identify the health economics and disparities related to DBS therapy, thereby helping clinicians identify ways to improve DBS treatment processes and patient outcomes.
Background: Many clinical questions about DBS therapy cannot be practically answered through traditional clinical trials methodology. RAD-PD will be conducted as a quality improvement project, a form of health effectiveness research that is focused on measuring and monitoring outcomes in order to secure positive change.
Methods/Design: This study has 2 phases. In the first phase, we will use an neuroimaging method called positron emission tomography and gradually escalating doses of varenicline to find the most appropriate dose for Parkinson disease patients. In the second phase, we will administer the selected dose of varenicline to Parkinson disease patients in a double-blind crossover trial. Laboratory measures of gait and balance will be obtained on and off varenicline. This will allow us to determine if varenicline, or similar drugs, should be pursued as treatments for Parkinson disease.
Relevance to Diagnosis/Treatment of Parkinson’s Disease: Relevance to Diagnosis/Treatment of Parkinson’s disease: The quality improvement design of this patient registry will generate large datasets that can provide insights into treatment patterns and related outcomes for DBS. Analysis of registry data will allow investigators to fill knowledge gaps in the current evidence base about DBS in PD, provide information that is applicable within a spectrum of clinical care environments, and yield recommendations for practice improvement that will enhance therapy outcomes for patients with Parkinson’s disease.