New, Innovative Parkinson’s disease Research Being Funded by APDA
For people impacted by Parkinson’s disease (PD) the search for answers – the causes, a cure, better treatments – may seem elusive, too slow, frustrating. But all of us at APDA will not give up our pursuit, and rather than be deterred, we are inspired, energized and hopeful about the progress that has been made. And we are particularly optimistic when we see the exciting new work being done by some of the brightest minds in PD and we are extremely proud to support these researchers with funding through our grant process.
Today, APDA announced our research grantees for the year ahead. Our grant recipients are working tirelessly to understand the complexities of PD in an effort to develop new treatments and eventually, a cure, and we are honored to support their work. This year APDA awarded $1.4 million in grants that will support a wide range of fascinating research. This year, we also awarded the first-ever APDA Diversity in
Parkinson’s Disease Research grant to help address the issues and disparities regarding PD in underserved populations – more info about this new grant below.
The APDA Scientific Advisory Board thoroughly vetted each application and chose these grantees very carefully. While the science can seem complicated and the medical jargon confusing, rest assured that this work is not only significant, but exciting as well. Below, I present the research proposals to you and point out why they are important.
Post-doctoral fellowships are awarded to support post-doctoral scientists whose research holds promise to provide new insights into our understanding of PD.
April Darling, PhD
University of Pennsylvania School of Medicine
Engineering therapeutic TRIM11 disaggregases
Major question to be answered: Can we create a molecule that efficiently prevents and dissolves aggregates of alpha-synuclein?
Why is this important? Such a molecule could serve as a new therapy for PD.
People with PD have protein deposits in their brain (Lewy bodies) which are composed of accumulated α-synuclein. Preventing α-synuclein aggregation and dissolving pre-formed aggregates may be an effective strategy for treating PD. A class of proteins known as protein disaggregases have the ability to dissolve protein aggregates. One recently identified disaggregase is TRIM11. This project aims to find the most effective variant of TRIM11 at dissolving aggregates and preventing clumping of α-synuclein.
Judit Pallos, Ph.D.
Oregon Health and Science University
Mechanisms of LRRK2-induced neurodegeneration
Major question to be answered: How does the protein Prospero, which is known to be involved in outgrowth of nerve cell projections, contribute to nerve cell death in an animal model of PD?
Why is this important? This work will further our understanding of why nerve cell death occurs in PD which may identify new targets for therapy,
Degeneration of the axon (the long projection of the nerve cell that extends out from the cell body to communicate with other nerve cells) is observed in the cells of people with PD as well as in animal models of the disease. Here, the role of the protein Prospero, known to control neuronal outgrowth, will be explored to understand how it contributes to neuron abnormalities in PD.
Monika Sharma, PhD
The Brigham and Women’s Hospital
Systems biology of a novel neuronal mitochondrial mechanism: relevance to Parkinson’s disease therapies
Major question to be answered: How does activation of the beta2 adrenergic receptor work to protect neurons from degeneration?
Why is this important? If we understand the cellular mechanisms that protect neurons from degeneration, therapies can be designed to enhance those mechanisms.
Dysfunction of the mitochondria, the energy producing machinery of the cell, is known to play a role in development of PD. In addition, previous work showed that activation of the b2 adrenergic receptor can protect cells from degeneration, possibly by down-regulating α-synuclein, a protein which abnormally accumulates in PD neurons. This study aims to determine whether activation of the b2 adrenergic receptor contributes to neuroprotection by activating specific mitochondrial pathways in dopamine neurons.
Diversity in Parkinson’s Disease Research Grant
We are particularly excited to award the first-ever Diversity in Parkinson’s Disease Research Grant. This grant was created to support the study of the health disparities or differences among under-represented PD communities. The grant was inspired by the APDA Diversity in Parkinson’s Disease Conference held in May 2019.
Chantale Branson, MD
Morehouse School of Medicine
Understanding racial demographics of Parkinson’s disease among African Americans
Major question to be answered: What is the prevalence and unique clinical features of PD in the African American community?
Why is this important? PD in the African American community has been under-studied, contributing to poorer PD outcomes in this population. Increased understanding of PD in the African American community will hopefully lead to better clinical outcomes.
Previous studies have shown racial disparities in the diagnosis and treatment of PD, with people of African descent, having delayed diagnosis, more severe symptoms at the time of diagnosis, inadequate treatment, and worse clinical outcomes compared to their Caucasian counterparts. While the impact of disparities in PD is defined, the reasons behind the differences are not well understood. This project will establish a database of African Americans with PD to help define the unique features of PD in this population and determine factors that may contribute to delays in the diagnosis of PD.
Research grants are awarded to investigators performing innovative PD research at major academic institutions across the United States.
Kevin Beier, PhD
University of California, Irvine
Mapping circuit-level pathology evoked by dopamine depletion
Major question to be answered: How is the communication within the basal ganglia altered as dopamine is lost and how do those changes contribute to development of PD?
Why is this important: Brain alterations in PD start prior to development of PD symptoms. Identification of these changes could serve as a biomarker of early disease and could guide development of therapies for early PD.
Using an experimental system that can track the connection between neurons in the brain, the project will aim to identify which neurons and pathways in the brain are altered during PD pathogenesis, and in what order.
J. Nicole Bentley, MD
University of Alabama at Birmingham
Investigating prefrontal biomarkers of action control and effects of theta-burst deep brain stimulation in Parkinson’s disease
Major question to be answered: What brain signal changes correlate with cognitive impairment in PD? Can these be altered with specific deep brain stimulation (DBS) parameters?
Why is this important? Cognitive impairment is very common in PD and currently is very difficult to treat successfully. This project aims to discover DBS parameters that could treat cognitive impairment in PD.
People with PD have reduced activity of various type of brainwaves or neuronal oscillations, which correlates with increased response times in cognitive tasks. In this project, people with PD receiving deep brain stimulation for their motor symptoms will perform cognitive tasks during the surgery and their brain waves will be recorded. This project seeks to understand the relationship between brain wave changes and cognition in PD and also seeks to determine if particular methods of DBS stimulation will change these brain wave patterns and improve cognition.
Annie Hiniker, MD, PhD
University of California San Diego
Elucidating pathways of LRRK2 turnover as therapeutic targets for Parkinson’s disease
Major question to be answered: What processes in the cell are responsible for destruction of LRRK2, a key protein in the development of PD?
Why is this important? Inhibiting LRRK2 is a treatment strategy that is being pursued for the treatment of PD, but there are concerns about unwanted effects of these treatments. This project aims to understand what is happening in the cell when LRRK2 is inhibited thereby bringing these treatments closer to the clinic.
Genetic mutation of the protein LRRK2 is the most common genetic cause of both sporadic and familial PD. LRRK2 is a kinase, an enzyme that places a phosphate groups on molecules. Mutations that cause PD increase LRRK2’s kinase activity. Because of this, LRRK2 kinase inhibitors have been developed as a possible therapy for PD. Unfortunately, all known LRRK2 kinase inhibitors cause increased degradation of the normal LRRK2 protein. This work will explore the cellular pathways by which LRRK2 kinase inhibition causes LRRK2 protein degradation.
Karen L. Eskow Jaunarajs, PhD
Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham
A cell type-specific transcriptional profile of the development of L-DOPA-induced dyskinesia
Major question to be answered: What changes occur in the brain as Levodopa induced dyskinesias (LIDs) develop?
Why is this important? Understanding the specifics of what happens over time in different brain locations as LIDs develop, can lead to strategies for halting this process.
Levodopa treatment can cause changes in the PD brain that can lead to the development of LIDs – extra, involuntary movements. Precisely what happens to cause LIDs is not known. This project will explore the changes in gene expression in different cell types over time as LIDs are developing to understand how and why they occur.
Andrew Sharp, PhD
Icahn School of Medicine at Mount Sinai
Identifying novel repeat expansions as a cause of Parkinson’s disease
Major question to be answered: Are tandem repeat expansions (strings of short repeating sections of DNA) a genetic cause of PD?
Why is this important? This project aims to discover new genetic causes of PD.
Expansions of tandem repeats are known to cause more than 30 different human neurological diseases, mostly late-onset neurodegenerative disorders such as Huntington’s disease and hereditary ataxias, which can show considerable clinical similarities with PD. This project will use newly-developed analysis approaches to look for tandem repeat expansions in genome sequencing data from thousands of individuals with PD and controls to determine if these DNA changes can cause PD.
Tips and Takeaways
- Every grant we fund has been reviewed by our Scientific Advisory Board. The grants listed above were selected with extreme care and determined to be the most meritorious.
- For the first time, we are funding a Diversity in Parkinson’s Disease Research This grant will investigate the unique features of PD in the African American community with the goal of improving clinical outcomes.
- All of the cutting-edge research described above is only possible due to the support and generosity of our donors. Click hereto help us in this critical mission.
- We encourage you to learn more about all of the research APDA has funded over the years.