APDA announces funding for 2019-2020 grants

It is that time of year – when APDA announces our research grantees for the 2019-2020 fiscal year. We are very proud of our grant recipients who each has a unique idea that will hopefully benefit the entire Parkinson’s disease (PD) community. This year APDA has awarded $1.7 million in grants that will support a wide range of fascinating research – including the investigation of T cells and their role in PD; genetic factors for PD in Hispanic populations; the potential for telehealth psychotherapy to alleviate depression in PD; and so much more.

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 application and chose these grantees very carefully. We are excited for these 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 and point out why they are important.

George C. Cotzias Fellowship

The George C. Cotzias Fellowship is APDA’s most prestigious grant. The award spans three years and is designed to fund a long-range project focused on PD.

Vikram Khurana, MD, PhD
Brigham and Women’s Hospital, Boston, MA
Molecular mechanisms of perturbed mRNA metabolism in alpha-synucleinopathy

Major question to be answered: How does α-synuclein mutation or over-expression affect mRNA regulation in PD?

Why is it important?: If α -synuclein is shown to change mRNA functioning, this could lead to the identification of new therapeutic targets and potential gene therapies.

In previous work Dr. Khurana explored genetic and physical interactions of α-synuclein, the protein that accumulates in the brains of people with PD. He discovered unexpectedly, that α-synuclein influences messenger RNA (mRNA), the intermediary molecule between DNA and the proteins that it encodes.

This project aims to understand the role of mRNA regulation or dysregulation in PD neurons. By using induced pluripotent stem cells (stem cells created from people with specific mutations in or over-expression of α –synuclein), Dr. Khurana will investigate the changes to mRNA biology that can be attributed to changes in α -synuclein.

Post-doctoral Fellowships

Awarded to support post-doctoral scientists whose research holds promise to provide new insights into the pathophysiology, etiology and treatment of PD.

Edward Griffin, PhD
University of Alabama at Birmingham, Birmingham, AL
The role of T cells in inflammation-induced neurodegeneration

Major question to be answered: What is the role of the particular immune cell, the T cell, in the destructive changes of the PD brain? 

 Why is this important?: If we understand how the T cell contributes to PD development, therapies that interfere with T cell function can be tried for people with PD.

It is known that inflammation in the brain is an important part of the pathological changes that accompany PD, but inflammation is a complex process involving multiple types of signals and immune cells. The precise makeup of the inflammation in PD is not completely understood. This project focuses on the role of T cells, one type of immune cell, and their role in PD.

Previous work has shown that when particular structures of α-synuclein are injected into the brains of rats, inflammation is triggered. In this project, the brain tissue of these rats will be studied to determine which types of immune cells are activated. Then, rats unable to produce T cells will be injected with these α-synuclein structures to determine if there is a difference in the neurodegeneration caused by the α-synuclein with and without T cells.

Livia Hecke Morais, PhD
California Institute of Technology, Pasadena, CA
Microbial-brain interactions in Parkinson’s disease neurodegeneration

Major question to be answered: How do the micro-organisms that live in the gut contribute to the motor deficits and increased α-synuclein seen in a mouse model of PD?

 Why is this important?: Understanding the relationship between gut bacteria and disease can help to design novel therapies that manipulate gut bacteria for the treatment of PD.

Research has shown that the microbiome, the collective body of micro-organisms that live in the gut, can be altered in different disease states. In a mouse model of PD, the microbiome has been linked to motor deficits, inflammation and increased α-synuclein pathology. It has recently been demonstrated that transferring the microbiome from patients with PD into a germ-free mouse model of PD can induce increased motor dysfunction. What is not understood is how this happens. This project will investigate whether specific genetic profiles or metabolic byproducts of the microbiome are associated with worsened motor function. The project will also look at whether the gut microbiome impacts brain energy use by interfering with the mitochondria, or the specialized structures of the cell that create energy.

Dorian Sargent, PhD
Van Andel Institute, Grand Rapids, MI
Novel molecular mechanisms of VPS35-linked Parkinson’s disease: D620N VPS35 knock-in mice

Major question to be answered: How does VPS35 which is mutated in some families with PD, contribute to the development of PD?

 Why is this important?: Understanding how VPS35 contributes to PD will help us broaden our understanding about what is happening in the PD nerve cells and can help us design new treatments that manipulate the function of VPS35.

Vacuolar Protein Sorting 35 (VPS35), is a component of a large protein complex in the neuron that helps to transport and recycle specific proteins. A specific mutation of this gene can run in families and causes PD that is indistinguishable from sporadic PD (unrelated to a specific mutation). Very little is known however, about how mutations of VPS35 change the function of VPS35 and how that contributes to PD. This study will use a mouse model with mutated VPS35 to investigate those unanswered questions. Interestingly, these mice develop abnormal accumulations of tau in the brain, and not α -synuclein, suggesting that understanding VPS35 biology may also have ramifications for neurodegenerative diseases that accumulate tau such as progressive supranuclear palsy (PSP).

Research Fellowships

Awarded to investigators performing innovative PD research at major academic institutions across the United States.

Brian Daniels, PhD
Rutgers, The State University of NJ, Piscataway, NJ
Investigating RIPK3 as a driver of inflammatory astrocyte activation in Parkinson’s disease

Major question to be answered: Does the RIPK family of proteins, which promote inflammation associated with Alzheimer’s disease and Amyotrophic lateral sclerosis, also contribute to inflammation in PD?

 Why is this important?: If we understand the processes by which RIPK signaling contributes to inflammation in PD, inhibitors of these proteins can be tried as new PD therapies.

Inflammation in the brain plays an important role in the pathologic changes of PD. Astrocytes, a cell type in the brain with a variety of functions, can become activated during the progression of PD and promote inflammation. Recent work has also shown that a group of proteins called Receptor Interacting Protein Kinases (RIPKs) are key players in promoting inflammation in a variety of neurodegenerative conditions, and inhibitors of RIPK signaling are currently in clinical trials for both Alzheimer’s disease and Amyotrophic lateral sclerosis (ALS). Increased RIPK activity has been observed in PD as well, but its role is not fully understood. This grant will study the specific role of RIPK3 signaling in the development of neuroinflammation in a PD mouse model.

Xianjun Dong, PhD
Harvard Medical School, Brigham and Women’s Hospital, Boston, MA
Circular RNAs: A novel link between genetic susceptibility and Parkinson’s disease?

Major question to be answered: Which circRNAs, a newly discovered class of RNA, are expressed in dopamine neurons and may be related to development of PD?

Why is this important?: By characterizing this newly-discovered component of dopamine cells and its relationship to PD, we may have a better understanding of what goes wrong in PD and be able to develop targeted RNA-based therapies.

Circular RNA (circRNA) is a recently discovered class of RNA (ribonucleic acid) which is enriched in the brain, primarily around the synapse – the space between two neurons. Much is not yet known about circRNAs, but they may be involved in how neurons speak to each other. This project aims to identify the circRNAs expressed in dopamine neurons, the nerve cells that are particularly susceptible in Parkinson’s disease (PD), and then determine which circRNAs are associated with PD based on when and how they are expressed.

Monica Driscoll, PhD
Rutgers, The State University of NJ, Piscataway, NJ
Identification of genes mediating a novel mitochondrial quality control mechanism impacted by Parkin

 Major question to be answered: How do exophers, a newly discovered garbage disposal mechanism in the nerve cell, form and select mitochondrial cargoes?

Why is this important?: 1) If we understand the basic mechanisms of how nerve cells get rid of what is determined to be garbage, we may understand how α-synuclein is transferred from one neuron to another; and 2) If exophers that dispose of mitochondria do not function properly in PD, then understanding how exophers form can help us to design new therapies for PD.

In previous work, Dr. Driscoll’s lab discovered that neurons in the model roundworm organism C elegans can “throw out” debris into the space outside the cell, in strikingly large membrane-surrounded vesicles named exophers. The exopher mechanism may have implications for how α-synuclein is discarded outside the cell, a process that potentially allows α-synuclein to then enter a neighboring cell, and from there, continue to propagate into other cells.

Mitochondria, or the specialized structures within the cell that produce energy, can also be disposed of in exophers in order for the neuron to maintain only healthy mitochondria within its boundaries. Mitochondrial dysfunction is known to be a key feature of PD, and mutations of particular proteins that are associated with development of PD, including Parkin, PINK1, and LRRK2 influence the removal of mitochondria via exophers. This could indicate that the exopher process that clears the cell of dysfunctional mitochondria may not function properly in PD. This grant will investigate which additional genes are responsible for processing the mitochondrial “garbage”.

Karen Nuytemans, PhD
University of Miami, Miami, FL
Genetic factors for Parkinson’s disease in Hispanics

Major question to be answered: What is the contribution of the PD genes that have already been identified in the Hispanic population?

Why is this important? By understanding the genetics of PD in a variety of populations, we will have a more complex and accurate understanding of all the genes that contribute to PD.

Most studies investigating the genetics of PD have been performed on non-Hispanic individuals of European descent. The Hispanic population, is a genetically diverse group with European, African and Amerindian ancestry. PD risk in this group is likely due to both genetic risk factors previously identified in non-Hispanic European descent patients as well as novel genetic factors present in the African and Amerindian lineages.  This study will initially aim to evaluate the frequency of known PD genes in the Hispanic population to determine the genetic contribution of known genes to PD risk in this population.

Mohammed Shahnawaz, PhD
University of Texas Health Sciences Center at Houston, Houston, TX
Detection of α -synuclein oligomers in blood for the diagnosis of Parkinson’s disease

Major question to be answered: Can a blood test for PD be invented that measures clusters of α-synuclein circulating in the blood?

Why is this important?: Having a blood test for PD will revolutionize diagnosis of PD and monitoring of disease.

PD does not have a reliable biomarker or biological feature that can indicate whether a person has the disease or not. It is known that α-synuclein clustering is a key disease feature found in the brains of people with PD, but accessing brain tissue is not a realistic way to make a diagnosis. It has been discovered that tiny amounts of α-synuclein clumps circulate in the blood. This project aims to work on a method to detect these clumps in the blood to create a blood test that can diagnose PD.

Bonnie Wong, PhD
Boston University, Boston, MA
Alleviating depression and cognitive impairment in Parkinson’s disease through telehealth psychotherapy.

Major question to be answered: Can CBT be done to treat depression and cognitive impairment in PD via telemedicine? 

Why is this important? If telemedicine does work to treat depression and cognitive impairment in PD, then many more people will be able to access mental health services.

Depression and cognitive impairment are very common non-motor features of PD. Cognitive behavioral therapy (CBT) can be an effective treatment, but there are many limitations to obtaining this type of therapy for people with PD. These include motor disability and transportation issues which make it challenging to come to weekly appointments, as well as a limited number of mental health professionals able to give this specialized care. This project will evaluate the feasibility and efficacy of performing CBT via telehealth, the delivery of health services through telecommunication technologies.

As I hope you can see from the grants described above, we are focused on identifying researchers early in their careers to attract them to the PD field, as well as to help established investigators pursue new and novel ideas. In many cases these APDA-funded projects produce significant pilot data, which has enabled researchers to apply for and receive large research grants from the National Institutes of Health (NIH) and other funding institutions. A past APDA-funded researcher, Beom-Chan Lee, just recently received a large grant from the NIH due to the work he was able to do with APDA’s support. Now he can continue his research project for several more years!

Tips & Takeaways

• Understanding the types of PD research underway is one more way to educate and empower yourself.
• APDA is very thoughtful in its grant selection process, choosing only those requests with significant merit.
• APDA funding can help researchers to develop their theories and thus apply for larger grants (from the NIH and other sources) that enable them to delve deeper into their research.
• The cutting-edge research described above is possible due to the support and generosity of our donors. Click here to help us in this critical mission.
• We encourage you to learn more about all of the research APDA has funded over the years.