The development of neuroprotective strategies for PD is a vital unmet need. Despite remarkable advances in the last fifteen years in the understanding of pathobiological mechanisms in PD, there are no known therapies available that slow the progression or alter the course of PD. The systemic nature of PD suggests new pre-clinical approaches are needed in order to identify pathways and associated therapeutics that might slow the progression of disease. As stated in the Conference and Recommendations Report to NINDS Council (PD2014), the community of investigators focused on PD now strives to create therapies that meaningfully slow or stop the disease mechanisms that underlie all symptoms of PD. Neuroinflammation is increasingly recognized as a critically important element of PD pathogenesis. The vision for this P20 Exploratory Grant is to create the team, environment, and capability to explore innate and adaptive immunity in PD. Currently, there are no Udall Centers of Excellence that focus on understanding neuroinflammatory mechanisms in PD. These studies will require a team with a combination of specialized expertise in neuroimmunology and neurodegenerative disorders. We request support to foster the development of new collaborations and to develop critical data both in PD subjects as well as in recently developed pre-clinical models of PD. The investigative team includes two established investigators in PD (Drs. David Standaert and Andrew West), and an established investigator from the field of neuroimmunology (Dr. Etty Tika Benveniste). We will explore neuro-inflammatory signaling, particularly the actions of myeloid cells, in pre-clinical models of PD as well as early human disease. It is expected that success in these exploratory studies will lead to the development of a future Udall Center of Excellence dedicated to understanding the roles of the innate and adaptive immune system in PD, with emphasis on pursuing points of therapeutic mediation and novel neuroprotection strategies.

Public Health Relevance

The vision for this P20 Exploratory Grant is to create the team, environment, and capability to explore innate and adaptive immunity in PD. The long term goal for this team is to establish a P50 Udall Center which will identify novel immunomodulatory treatments to slow the progression of PD and to complement ongoing studies in existing Udall Centers by establishing a focus of expertise in neuroinflammation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory Grants (P20)
Project #
1P20NS092530-01
Application #
8936250
Study Section
Special Emphasis Panel (ZNS1)
Program Officer
Sieber, Beth-Anne
Project Start
2015-07-01
Project End
2017-06-30
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Neurology
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Delic, Vedad; Chandra, Sidhanth; Abdelmotilib, Hisham et al. (2018) Sensitivity and specificity of phospho-Ser129 ?-synuclein monoclonal antibodies. J Comp Neurol 526:1978-1990
Harms, Ashley S; Thome, Aaron D; Yan, Zhaoqi et al. (2018) Peripheral monocyte entry is required for alpha-Synuclein induced inflammation and Neurodegeneration in a model of Parkinson disease. Exp Neurol 300:179-187
Gwinn, Katrina; David, Karen K; Swanson-Fischer, Christine et al. (2017) Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program. Biomark Med 11:451-473
Harms, Ashley S; Delic, Vedad; Thome, Aaron D et al. (2017) ?-Synuclein fibrils recruit peripheral immune cells in the rat brain prior to neurodegeneration. Acta Neuropathol Commun 5:85
West, Andrew B (2017) Achieving neuroprotection with LRRK2 kinase inhibitors in Parkinson disease. Exp Neurol 298:236-245
Abdelmotilib, Hisham; Maltbie, Tyler; Delic, Vedad et al. (2017) ?-Synuclein fibril-induced inclusion spread in rats and mice correlates with dopaminergic Neurodegeneration. Neurobiol Dis 105:84-98
Qin, Hongwei; Buckley, Jessica A; Li, Xinru et al. (2016) Inhibition of the JAK/STAT Pathway Protects Against ?-Synuclein-Induced Neuroinflammation and Dopaminergic Neurodegeneration. J Neurosci 36:5144-59
Ponnazhagan, Ranjani; Harms, Ashley S; Thome, Aaron D et al. (2016) The Metabotropic Glutamate Receptor 4 Positive Allosteric Modulator ADX88178 Inhibits Inflammatory Responses in Primary Microglia. J Neuroimmune Pharmacol 11:231-7
Litvan, Irene; Lees, Peter S J; Cunningham, Christopher R et al. (2016) Environmental and occupational risk factors for progressive supranuclear palsy: Case-control study. Mov Disord 31:644-52
West, Andrew B; Cookson, Mark R (2016) Identification of bona-fide LRRK2 kinase substrates. Mov Disord 31:1140-1

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