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Principal Investigator: VESNA D GAROVIC
Organization: MAYO CLINIC ROCHESTER
Fiscal Year: 2024
Award: $200,633
Funding agency: National Center for Advancing Translational Sciences
OVERALL: Project Summary/Abstract
Mayo Clinic is one of the largest not-for-profit, academic health systems, top-ranked for quality more often than
any other health care organization. It has integrated operations in 5 U.S. states, and more than 1 million people
came to Mayo Clinic for care last year. Clinical and translational science (CTS) is a fundamental and highly
valued element of Mayo Clinic; indeed, all research at Mayo Clinic is directed towards translation of scientific
knowledge to improve patient care, with almost 60% of our NIH funding base classified as clinical research or
trials. In recognition of the importance of continued advances in CTS to the Mayo Clinic mission, our institutional
leadership has entrusted the Mayo Clinic Center for Clinical and Translational Sciences (CCaTS) to be the engine
of translational innovation and the institutional advocate for CTS and translational research. CCaTS has served
as a CTS innovation incubator for numerous efforts that were created with CCaTS funding and are now
supported by the institution. The overall vision of CCaTS is to enable high-quality, team-based multidisciplinary
research that accelerates clinical trial innovation, facilitates digital health transformation, and partners with our
stakeholders and communities to improve patient care and health for all people. Our team-based culture has
been described as one of “boundarylessness,” wherein organizational barriers are removed to enable talent,
innovation, and knowledge to converge where needed. In this context and that of our longstanding commitment
to patient-focused research, we are uniquely positioned to accomplish the following Specific Aims. In Aim 1, we
will simplify and accelerate the work of translation to improve health for all by advancing clinical trial innovations
and digital health transformations, streamlining methods and processes, and developing novel informatics
solutions that increase efficiency and drive implementation of discoveries that improve health and promote health
equity. In Aim 2, we will enhance our education programs through the expanded reach of competency-based,
learner-focused solutions, training a diverse, inclusive, multidisciplinary CTS workforce to be prepared to address
the urgent health care needs of all communities in a rapidly changing environment. In Aim 3, we will engage
local community members and patients to be active partners in translational teams, expanding research
capabilities of underserved communities, including rural populations. Our goal is to improve health and reduce
health inequities by helping these communities realize the benefits of CTS. In Aim 4, we will expand national
and regional partnerships and strengthen collaborative CTS networks in all aspects of CTS and education,
focusing on sharing innovative approaches and prioritizing diversity, equity, and inclusion, with the goal of
improving human health and advancing health equity. In summary, sustained investment in CCaTS will enable
us to continue to meet ongoing and emergent challenges in health care for all, as exemplified by our response
to support communities through the COVID-19 crisis.
Evolving Strategies for PD: Investigating STN DBS as a Neuroprotective Intervention
Parkinson’s disease (PD) is a severely debilitating neurodegenerative disorder that affects more than 10 million
people worldwide with approximately $52 billion spent yearly in the United States. Presently, there is no cure for
PD and potential neuroprotective strategies failed to properly delay the evolution of the disease. For this reason,
the prevalence of PD has doubled in the past 25 years and it is estimated that the number of PD cases will
surpass 13 million in 2040 unless more effective neuroprotective therapeutics are brought to clinical use. Deep
brain stimulation of the Subthalamic Nucleus (STN DBS), a surgical intervention in mid- to advanced-stage PD,
may represent a safe and effective neuroprotective strategy for PD based on encouraging results from animal
research. Establishment of STN DBS as an approved neuroprotective strategy requires rigorous translational
research that builds on basic science research of the neuroprotective mechanism of DBS to allow therapy
optimization in the clinical scenario. Here, we adopt a translational approach to characterize the mechanisms
whereby STN DBS promotes neuroprotection and delays the progression of the disease while identifying
conditions that can maximize its neuroprotective effects. In Aim 1 we will use a rat model of PD to determine the
molecular and network-wide targets of STN DBS and their relative contribution to delay neurodegeneration. In
Aim 2 we will deliver electrical stimulation directly to cells that overexpress α-synuclein, a toxic protein that
aggregates and can lead to neuronal loss in PD to determine effective stimulation parameters that successfully
enhance key neuroprotective mechanisms. In summary, these aims will move the neuromodulation and
neurodegeneration fields forward by characterizing intricate molecular, cellular, and network-wide
neuroprotective mechanisms of STN DBS while providing a novel translational framework to allow further therapy
optimization for clinical application.
Terms: <Abscission><Acceleration><Address><Adopted><Advocate><Affect><Age><Amentia><Animal Experimental Use><Animal Experimentation><Animal Research><Antisense Agent><Antisense Oligonucleotides><Area><Assay><Attenuated><Basic Research><Basic Science><Behavior><Bio-Informatics><Bioassay><Biochemical><Bioinformatics><Biological Assay><Bradykinesia><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><Caring><Cell Aging><Cell Body><Cell Senescence><Cells><Cellular Aging><Cellular Senescence><Characteristics><Chronic><Classification><Clinic><Clinical><Clinical Research><Clinical Sciences><Clinical Skills><Clinical Study><Clinical Trials><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Common Rat Strains><Communities><Competence><Complement><Complement Proteins><Complex><DA Neuron><DNA Molecular Biology><Data><Deep Brain Stimulation><Degenerative Neurologic Disorders><Dementia><Deterioration><Diagnosis><Disease><Disease Progression><Disorder><Disturbance in cognition><Dopamine neuron><Dysfunction><E-stim><Early Diagnosis><Economic Income><Economical Income><Education><Educational aspects><Electric Stimulation><Elements><Environment><Evolution><Excision><Extirpation><FDA approved><Financial Hardship><Functional disorder><Funding><Goals><Hallucinations><Health><Health Inequity><Health system><Healthcare><Histologic><Histologically><Hortega cell><Human><Immunization><Impaired cognition><Impairment><In Vitro><Income><Incubators><Inequalities in Health><Inequities in Health><Inflammation><Inflammatory><Informatics><Institution><Interdisciplinary Research><Interdisciplinary Study><Intervention><Intervention Strategies><Investments><Knowledge><Leadership><Mentorship><Metabolic><Methods><Microglia><Mission><Modeling><Modern Man><Molecular><Molecular Biology><Motor><Movement><Multidisciplinary Collaboration><Multidisciplinary Research><Muscle Rigidity><Muscular Rigidity><NAC precursor><NIH><National Institutes of Health><Nerve Cells><Nerve Degeneration><Nerve Unit><Nervous System Degenerative Diseases><Neural Cell><Neural Degenerative Diseases><Neural degenerative Disorders><Neuroblastoma><Neurocyte><Neurodegenerative Diseases><Neurodegenerative Disorders><Neurologic Degenerative Conditions><Neuron Degeneration><Neurons><Neurosciences><Newly Diagnosed><Operative Procedures><Operative Surgical Procedures><Oxidative Stress><PARK1 protein><PARK4 protein><Paralysis Agitans><Parkinson><Parkinson Disease><Pathway interactions><Patient Care><Patient Care Delivery><Patients><Persons><Phenotype><Physiopathology><Position><Positioning Attribute><Prevalence><Primary Parkinsonism><Process><QOL><Quality of life><Radiation><Rat><Rats Mammals><Rattus><Recurrence><Recurrent><Removal><Replicative Senescence><Research><Rural Population><Rural group><Rural people><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SNCA><SNCA protein><STN stimulation><Safety><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Sight><Social Interaction><Structure><Surgical><Surgical Interventions><Surgical Procedure><Surgical Removal><System><Systematics><Talents><Testing><Therapeutic><Training><Translational Research><Translational Research Enterprise><Translational Science><Translations><Tremor><United States><United States National Institutes of Health><Urinary Incontinence><Urinary Retention><Vision><Work><a-syn><a-synuclein><ages><alleviate symptom><alpha synuclein><alpha synuclein gene><alphaSP22><ameliorating symptom><animal experimentations><antisense oligo><asyn><attenuate><attenuates><base><bases><behavior test><behavioral test><body movement><brain circuitry><care for patients><care of patients><caring for patients><clinical applicability><clinical application><clinical center><clinical efficacy><cognitive dysfunction><cognitive loss><complementation><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><cost><decrease symptom><degenerative diseases of motor and sensory neurons><degenerative neurological diseases><digital health><disability><disease phenotype><diversity, equity, and inclusiveness><dopaminergic neuron><early biomarkers><early detection><early detection biomarkers><early detection markers><electrostimulation><equity, diversity, and inclusion><falls><fewer symptoms><financial adversity><financial burden><financial distress><financial insecurity><financial strain><financial stress><gitter cell><health care><health care organization><health care service organization><health equity><health equity promotion><health inequalities><healthcare organization><healthcare service organization><improved><incomes><inflammation marker><inflammatory marker><innovate><innovation><innovative><insoluble aggregate><interventional strategy><member><mesoglia><microglial cell><microgliocyte><motor symptom><multidisciplinary><neglect><nerve cell death><nerve cell loss><neural control><neural degeneration><neural inflammation><neural regulation><neurodegeneration><neurodegenerative><neurodegenerative illness><neuroinflammation><neuroinflammatory><neurological degeneration><neuromodulation><neuromodulatory><neuron cell death><neuron cell loss><neuron death><neuron loss><neuronal><neuronal cell death><neuronal cell loss><neuronal death><neuronal degeneration><neuronal loss><neuroprotection><neuroprotective><neuroregulation><non A-beta component of AD amyloid><non A4 component of amyloid precursor><novel><operation><operations><overexpress><overexpression><parkinsonian mouse><parkinsonian rat><parkinsonian rodent><pathophysiology><pathway><perivascular glial cell><posture instability><prevent><preventing><programs><promote health equity><protein aggregate><protein aggregation><reduce symptoms><relieves symptoms><resection><response><rural individual><scRNA-seq><senescence><senescent><senescent cell><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><single cell RNA-seq><single cell RNAseq><single cell expression profiling><single cell transcriptomic profiling><single-cell RNA sequencing><skills><subthalamic nucleus stimulation><surgery><symptom alleviation><symptom reduction><symptom relief><therapy optimization><transcriptomics><translation><translation research><translation research enterprise><translation strategy><translational approach><translational framework><translational investigation><translational research program><translational strategy><treatment optimization><under served community><underserved community><visual function><α synuclein gene><α-syn><α-synuclein>