What do virtual reality and menopause have in common? APDA’s new grants are announced
Last May, I wrote about the process by which APDA’s Scientific Advisory Board chooses which research grants to fund. It is fascinating to discuss and consider thought-provoking proposals from across the country from researchers dedicated to trying to solve the difficult puzzle that is Parkinson’s disease (PD).
It is that time of year – when APDA announces our research grantees for the 2018-2019 fiscal year. We are very proud of our grant recipients who each has a unique idea that will hopefully serve to benefit the entire PD community.
While a lot of the scientific terminology can seem like a foreign language, and the ideas can sometimes seem obscure to a lay person, rest assured that the APDA Scientific Advisory Board thoroughly vetted each and every application and chose these grantees very carefully. We are excited for these scientists and researchers to dig deep into their work and have hope for meaningful outcomes that can make a difference for people living with PD. Below, I have tried to explain the research proposals to you.
Here are our awardees and what they will be researching:
George C. Cotzias Fellowship
Aasef Shaikh, MBBS, PhD, Cleveland VA Medical Center and Case Western Reserve University, Cleveland, OH
The influence of basal ganglia, thalamus, and cerebellum network on discordant visual input induced gait disorder in Parkinson’s disease (PD)
This project aims to understand the biological underpinnings of poor gait and imbalance in PD. Using virtual reality, both patients and controls will be subject to visual signals that conflict with other sensory inputs. Studying each group’s reaction will help to further the understanding of the abnormal brain circuitry in PD. In addition, it will help to develop new deep brain stimulation (DBS) strategies to manipulate that circuitry and improve gait. The ultimate goal of this work is to develop DBS technologies that can improve gait dysfunction in PD, a feature of PD that often does not respond to current pharmacologic and DBS methods.
Daniel Joyce, PhD, Stanford University, Stanford, CA
Pupil-based biomarkers of Parkinson’s disease
It has been shown that people with Parkinson’s disease have a slower response of their pupil to light. This research works to develop a test of the pupil’s response to light, and determine how it correlates to disease severity, to be used as a biomarker of PD. Currently, there is no definitive test that can be done to follow PD disease progression over time. This test could turn out to be a simple way to do that.
Giulietta Riboldi, MD, New York University School of Medicine, New York, NY
Role of GBA mutations in the pathogenesis of Parkinson’s disease
Glucocerebrosidase (GBA) mutations on both copies of human DNA causes Gaucher’s disease. Data has accumulated to suggest that mutations in this protein, either on one or both copies of DNA, is associated with an increased risk of PD. This project aims to characterize the patients with PD that also harbor this mutation and investigate the relationship between GBA and PD. If researchers understand how GBA mutations contribute to development of PD, they can design treatments to interfere with these processes.
Tim Bartels, PhD, The Brigham and Women’s Hospital, Boston, MA
Alpha-synuclein related lipid pathology in Parkinson’s disease
Alpha-synuclein molecules can exist in a number of structures, some of which abnormally clump into Lewy bodies and others which do not. This study investigates lipids, or fat molecules, that play a major role in cell structure, and their role in stabilizing alpha-synuclein into particular structures.
Christopher Bishop, PhD, Binghamton University, Binghamton, NY
Targeting the Pedunculopontine Tegmental Nucleus to Optimize Treatment of Parkinson’s Disease
This study investigates the function of a nucleus in the brainstem called the Pedunculopontine Tegmental Nucleus (PPN) and attempts to decipher its role in modulating motor and non-motor functions of the brain and its relationship to PD.
Shu Chen, PhD, Case Western Reserve University, Cleveland, OH
Novel knock-in models linking Rab phosphorylation to neurodegeneration in PD
Leucine repeat rich kinase 2 (LRRK2) mutations are a risk factor for PD. LRRK2 is a kinase, or a protein, that adds phosphate groups onto other proteins. Figuring out what proteins are phosphorylated by LRRK2 and what happens in the cell after that, is essential to figuring out why LRRK2 mutations cause PD. This work uses a simple organism, known as C elegans, to work out these cellular events.
Elizabeth Disbrow, PhD, Louisiana State University Health Sciences Center, Shreveport, LA
Diversity in biomarker discovery
Specific features on brain MRI may be able to act as biomarkers associated with disease progression. In this study, MRI and clinical data will be collected from both black and white PD patients. The study will investigate whether particular MRI features correlate with measures of disease severity across racial groups.
Yuanfang Guan, PhD, University of Michigan, Ann Arbor, MI
Digital biomarkers for monitoring Parkinson’s disease
The study’s goal is to generate an algorithm to analyze voice and movement information gleaned from a mobile device to determine PD diagnosis and severity. Such an algorithm could serve as a PD biomarker.
Mallory Hacker, PhD, Vanderbilt University Medical Center, Nashville, TN
Investigating long-term clinical outcomes of Subthalamic Nucleus Deep Brain Stimulation in early stage Parkinson’s Disease
A clinical trial was conducted between the years of 2006-2014, that investigated whether Deep Brain Stimulation (DBS) should be performed on patients in early stages of PD, as opposed to standard practice in which DBS is performed at more advanced stages of PD. The patients in the trial are beginning to meet the 10-year mark after surgery and this study aims to test these patients to determine the long-term effects of DBS done in this unique population. One hypothesis that is being explored is that DBS, if performed early enough, will change the course of the disease and improve long-term prognosis.
Magdalena Ivanova, PhD, University of Michigan, Ann Arbor, MI
Biochemical and structural studies of α-synuclein fibrils derived from brain tissues with Parkinson’s disease and Dementia with Lewy bodies with Alzheimer’s disease
α-synuclein molecules can exist in a number of structures. This study aims to study post-mortem brains of people who had only Lewy bodies in their brains and those who had both Lewy bodies and Alzheimer’s changes in their brains and investigate whether the presence of Alzheimer’s changes in the brain can affect the way α-synuclein accumulates.
Cameron Jeter, PhD, The University of Texas Health Science Center, Houston, TX
Protective role of the oral microbiome in Parkinson’s disease
The impact of the microbiome (the trillions of bacteria that inhabit the human gut) on PD is under intense investigation. This study aims to 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.
Eunsung Junn, PhD, Rutgers, The State University of New Jersey, Piscataway, NJ
In vivo identification of microRNAs associated with α-synuclein mRNA
MicroRNAs are small molecules that decrease production of a particular protein in the cell by binding to messenger RNA (mRNA). This study aims to identify microRNAs that bind α-synuclein mRNA and thereby serve to decrease alpha-synuclein production. Decreasing α-synuclein production may be one way to decrease Lewy body formation, the pathologic hallmark of PD.
Roberta Marongiu, PhD, Weill Cornell Medical College, New York, NY
Menopause as an important transition state in the susceptibility to Parkinson’s disease
Women develop PD at a slightly lower rate than men, at a ratio of about 2:3, but that rate evens out as women age. It has been hypothesized that the reason behind this epidemiological data is that estrogen is protective of the neurons, and that protection lifts during menopause. This project aims to characterize a mouse model of PD which has been subject to accelerated ovarian failure and study α-synuclein aggregation, inflammation, neurodegeneration, and motor deficits as menopause occurs.
Talene Yacoubian, MD, PhD, University of Alabama at Birmingham School of Medicine, Birmingham, AL
Rab27b as a potential regulator of α-synuclein spread
This project aims to study the events in the cell that cause α-synuclein to abnormally accumulate. Rab27b is being studied as a protein within the cell that is meant to clear abnormal α-synuclein. If this is confirmed, therapies that could enhance the action of Rab27b may be useful for treating PD.
For more detailed information on each project, please click here.
- Investigations to further PD research takes many shapes and forms: e.g. studies of cells, animal models, human biospecimen, imaging, mobile device data and more. Creativity is the first step in coming up with a way to help further our understanding of PD.
- Finding a biomarker for PD would be advantageous to help physicians diagnose and monitor the progression of PD. A number of our projects have this as a goal.
- We are only able to fund this research because we receive donations from dedicated people like you. If you would like to support this critical work, please click here.