On September 8, 2022, APDA announced 27 new research grants for the year ahead. Our grant recipients are working tirelessly to understand the complexities of Parkinson’s disease (PD) to develop new treatments and eventually, a cure. We are honored to support our researcher’s work. We awarded $2.35 million to support cutting-edge PD research for the 2022-2023 year – a 25% increase in funding from the previous year.
The APDA Scientific Advisory Board thoroughly vetted each application and chose these grantees very carefully. The funded research projects study a range of important topics including:
- Understanding the molecular underpinnings of anxiety in PD
- Probing the role of DNA damage in causing genetic mutations in PD
- Testing the use of augmented reality in treating freezing of gait
Grants have been awarded in the form of four Post-Doctoral Fellowships, thirteen Research Grants, one Diversity in Parkinson’s Disease Research grant, eight APDA Centers for Advanced Research, and one George C. Cotzias Memorial Fellowship.
Below, I present the research projects APDA will be funding and specify why they are important for the PD community. You can click on any of the researchers below to learn more about them and their work.
The 2022-2023 APDA Parkinson’s Disease Research Grants and Fellowships:
The George C. Cotzias Fellowship
The George C. Cotzias Fellowship is APDA’s most prestigious award and is granted to a young physician-scientist with exceptional promise who is establishing a career in research, teaching, and clinical services relevant to PD. The award spans three years and is designed to fund a long-range project focused on PD. This year’s awardee is:
Gary Ho, MD, PhD
Leveraging protein palmitoylation to correct vesicle trafficking defects in Parkinson disease.
Brigham and Women’s Hospital, Boston MA
Major question to be answered:
Can enzymes that add the fat molecule palmitate to proteins (palmitoyltransferases) correct vesicle trafficking defects caused by α -synuclein in PD?
Why is this important?
α-synuclein aggregation can distort the shape of vesicles – the bubble-like structures that transport cargo within the nerve cell. Palmitoylation can restore the normal curve of the vesicles. If palmitoylation improves the structure and function of vesicles in these studies, drugs or gene therapy targeting palmitoylation may be possible new therapies for PD.
Diversity in Parkinson’s Disease Research Grants
These are one-year grants to study the health inequities and/or differences among under-studied PD communities, across the spectrum of ethnicity, ancestry, geography, socioeconomic conditions, and gender. This year’s awardee is:
Erin Foster, PhD
Understanding engagement in research, clinical care, and community services among people of color with Parkinson disease.
Washington University, St, Louis, MO
Major question to be answered:
How can we increase health equity and reduce health disparities among people with PD?
Why is this important?
Underrepresentation of people of color is widespread in PD research and care. It is a significant problem because it limits our understanding of PD, impedes the generalizability and impact of PD-related research findings, and reduces the quality and outcomes of patient care for all people with PD. This project will form the foundation for the development of effective engagement strategies to improve representation, diversity, and inclusion in future work. Ultimately, it will promote the translation of scientific discoveries into practice and improve the quality of research and care, health, and well-being of all people with PD.
Post-Doctoral Fellowships
These fellowships are awarded to support post-doctoral scientists, who recently completed their graduate degree work, and whose research holds promise to provide new insights into the pathophysiology, etiology, and treatment of Parkinson’s disease. This year’s awardees are:
Tyler Camp, PhD
α-synuclein oligomerization and membrane localization in Parkinson’s disease.
University of Illinois Urbana-Champaign, Champaign, IL
Major question to be answered:
How do the size and location of α-synuclein clusters affects their toxicity?
Why is this important?
The project seeks to understand the relationship between α-synuclein cluster size and toxicity which can provide guidance for developing treatments for PD. For example, if the work reveals that smaller clusters are more harmful, this knowledge will guide drug development and therapeutic efforts toward eliminating smaller clusters rather than targeting larger ones. On a more fundamental level, understanding how cluster size impacts its potential to do damage, will give clues as to how PD might be initiated or evolve. Experiments that target α-synuclein to cell membranes will also help increase the understanding of whether these interactions are harmful and allow for the design of therapies to limit toxicity.
Stephan Grimaldi, MD, PhD
Longitudinal changes of brainstem-based biomarkers of prodromal Parkinson’s disease with Ultra-High Field MRI.
Massachusetts General Hospital, Boston, MA
Major question to be answered:
What long term changes of brain biomarkers of neurodegeneration, detected by a 7 Tesla MRI, are present in the prodromal phase of Parkinson’s disease?
Why is this important?
This project aims to identify early biomarkers of neurodegeneration with the goal of making early diagnosis a reality. Those who are diagnosed early can be included in clinical trials of potential neuroprotective agents. The same early biomarkers of neurodegeneration can then be used to monitor the response to the therapeutic intervention, thereby accelerating the development of therapeutics.
Anastasia Kuzkina, MD
Developing human IPSC models for examining host-strain interactions in synucleinopathy.
Brigham and Women’s Hospital, Boston, MA
Major question to be answered:
Do different strains of α-synuclein contribute to the variability in their aggregation and toxicity in different brain cell types? Does this contribute to the differences between PD and the related disorder Multiple system atrophy?
Why is this important?
This research will systematically analyze the effects of different α-synuclein aggregates in different brain cells to gain insight into the disturbances in biology that underlie different synuclein diseases. We will closely model the pathology seen in patients which could also shed light on which disease the treatment is likely to work in and thereby facilitate development of tailored therapies.
Andrew Zimnik, PhD
Role of basal ganglia output in acquiring and executing complex motor skills.
Columbia University, New York, NY
Major question to be answered:
What role does the basal ganglia play in initial learning and production of new movements?
Why is this important?
The ability to reverse the motor symptoms of PD would be greatly improved by a better understanding of the basal ganglia’s computational role in the healthy brain. If we can characterize the normal function of the cortico-basal ganglia circuit, we can better develop pharmacologic and surgical treatments to restore that function.
Research Grants
Research grants are awarded to investigators performing innovative PD research. This year’s awardees are:
Eamonn Dickson, PhD
α-synuclein dependent remodeling of membrane contact sites as a driver of Parkinson’s Disease neurotoxicity.
University of California, Davis. Davis, CA
Major question to be answered:
How does α-synuclein aggregation alter the structure and function of calcium channel domains at membrane contact sites – regions where internal membranes within the neuron contact each other – and how do these alterations precipitate neurodegeneration?
Why is this important?
Understanding how α-synuclein alters the membrane contact sites is critical and will help to determine how PD neurodegeneration progresses at the molecular level and interferes with inter-organelle communication. By defining mechanisms through which α-synuclein alters these membrane contact sites to increase dopamine neuron vulnerability, we can selectively target these sites with the aim of slowing the progressive neurodegeneration of PD.
Ronald Emeson, PhD
ADAR-Mediated LRRK2 Therapeutics in Parkinson’s Disease.
Vanderbilt University, Nashville, TN
Major question to be answered:
Can the power of the cell’s RNA editing repair machinery (Adenosine Deaminases Acting on RNAs or ADARs) be harnessed to correct a common genetic mutation in PD?
Why is this important?
The goal of these studies is the pre-clinical development of ADAR-recruiting RNAs as a new therapeutics tool to correct a common genetic mutation associated with PD.
Sunil Kumar, PhD
Therapeutic Validation of Novel Targets Associated with Parkinson’s Disease.
University of Denver, Denver, CO
Major question to be answered:
Can drug-like ligands be identified that can specifically target and disrupt the aggregation of α-synuclein, a process that is directly associated with development of PD?
Why is this important?
Identification of new molecules that disrupt the α-synuclein aggregation process will pave the way for novel and effective treatments for PD.
Gabsang Lee, PhD
In vitro and in vivo efficacy of hit compound selected from OASIS drug screening platform.
Johns Hopkins University School of Medicine, Baltimore, MD
Major question to be answered:
What is the potential therapeutic effect of a drug candidate, recently selected from a novel drug screening platform, that decreases the aggregation of α-synuclein?
Why is this important?
If successful, the proposed study will provide a new drug candidate for PD with a clear mechanism of action and associated pre-clinical data.
James Liao, MD, PhD
External vs internal-triggered augmented-reality visual cues to treat freezing of gait.
Cleveland Clinic, Cleveland, OH
Major question to be answered:
Can Augmented Reality (AR) cues be used to ameliorate freezing of gait (FOG) in PD?
Why is this important?
This will be the first study to determine if AR cues can improve FOG and could lead to widespread adoption of AR assistive cueing devices to treat FOG. In addition, by comparing FOG propensity across different cuing mechanisms, we may gain insight into the mechanisms of FOG, which are still incompletely understood. Ultimately, this project will lead to reliable treatments for FOG that improve quality of life and safety for people with PD.
Michael Lodato, PhD
Single-cell whole genome sequencing analysis of DNA damage and somatic mutation in the human Parkinson’s disease brain.
University of Massachusetts Chan Medical School, Worcester, MA
Major question to be answered:
What role do somatic mutations play in the development of PD?
Why is this important?
The analysis of somatic mutations in other disease states, such as cancer, has identified new and unexpected treatments. The mutation signature analysis that will be explored in this project may similarly identify therapeutic interventions for PD.
Ryan Roemmich, PhD
An automated mHealth approach for video-based motor assessment in Parkinson’s disease.
Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD
Major question to be answered:
Can efficient smart-phone based tools be developed that provide a useful and accurate motor assessment in people with PD?
Why is this important?
The new tools will provide data about patients’ movement patterns and ultimately, improve their clinical care. These tools can enable remote assessment of motor function, as they require only readily accessible household devices (e.g., smartphones, tablets) that can be implemented in virtually any setting, including the home and clinic. If successful, this proposal could lead to a paradigm shift in the way that movement in people with PD is measured.
Hiroaki Sekiya, MD, PhD
Differential protein and gene expression by digital spatial profiling in neurons with synuclein oligomers or Lewy bodies.
Mayo Clinic Jacksonville, Jacksonville, FL
Major question to be answered:
What is the total impact of α-synuclein oligomers and Lewy bodies on neurons in PD?
Why is this important?
The research aims to reveal the pathological roles of both early and late stage α-synuclein aggregates and can lead to discovery of new biomarkers and possibly new therapeutic targets for PD.
Martine Tetreault, PhD
Regulation of aberrant immunity in Parkinson’s disease by Stearoyl-CoA Desaturase.
Centre Hospitalier de l’Université de Montréal, Montreal, Quebec, Canada
Major question to be answered:
Can altering the fat metabolism in peripheral immune cells reduce the inflammatory signals in PD?
Why is this important?
This study will help to determine if directly altering fat metabolism in peripheral immune cells can be an effective treatment for PD.
Nicolas Tritsch, PhD
Revealing how striatal circuits gradually change as dopamine neurons degenerate.
New York University School of Medicine, New York, NY
Major question to be answered:
How do neurons that normally receive dopamine signaling gradually change as the degeneration of dopamine-producing neurons progresses?
Why is this important?
By revealing the molecular changes that define how dopamine-sensing neurons adapt to different degrees of dopamine-producing neuron degeneration, this work will provide novel insights into the pathophysiology of PD and enable the development of novel therapeutic approaches to prevent or reverse the onset of motor symptoms or the development of levodopa-induced dyskinesia.
Hisashi Umemori, MD, PhD
The nigrostriatal-specific dopaminergic synapse organizer and Parkinson’s disease.
Boston Children’s Hospital, Boston, MA
Major question to be answered:
Why are only the dopaminergic neurons of the substantia nigra – and not the ventral tegmental area – targeted in PD?
Why is this important?
The discovery of key molecules that regulate the differential susceptibility of dopaminergic neurons holds excellent potential for the discovery of novel drug targets and the development of promising neuroprotective treatment strategies for PD.
Laura Volpicelli-Daley, PhD
mGluR4 activation to rescue amygdala defects caused by aggregated alpha-synuclein.
University of Alabama at Birmingham. Birmingham, AL
Major question to be answered:
How do abnormal aggregates of α-synuclein disrupt neurotransmission in the amygdala and contribute to cognitive and psychiatric dysfunction in PD?
Why is this important?
If successful, this project could determine if specific pharmacologic compounds could rescue defects in the amygdala and prevent development of cognitive and psychiatric disturbances in PD.
Scott Waldman, MD, PhD
Targeting GUCY2C for Neuroprotection in Experimental Parkinson’s Disease.
Thomas Jefferson University, Philadelphia, PA
Major question to be answered:
Can GUCY2C activation by linaclotide block brain cell toxicity in PD?
Why is this important?
The proposed studies seek to define a new mechanism in which activation of GUCY2C by linaclotide promotes mitochondria function and potentially prevents neurodegeneration. Because linaclotide is already FDA-approved, these studies could be rapidly translated into new therapeutic strategies for 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.
- While some of the scientific terminology might be hard to follow, these research projects are incredibly exciting and have the potential to help make significant progress in the fight against Parkinson’s disease.
- The cutting-edge research described above is only possible due to the support and generosity of our donors.
- We encourage you to learn more about the research APDA has funded over the years.