ELUCIDATING IMMUNE AND MICROGLIAL DYNAMICS IN ALZHEIMER'S DISEASE WITH ADVANCED ORGANOID MODELS. - PARKINSO…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_K00AG068509_075
- FAIN
- K00AG068509
- Recipient
- UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $230,341
- Period
- Sep 1, 2020 – Jan 31, 2028
- Fiscal year
- 2024
- Place of performance state
- NC
- Source file
- FY2024_All_Assistance_Full_20261006.zip
Description
ELUCIDATING IMMUNE AND MICROGLIAL DYNAMICS IN ALZHEIMER'S DISEASE WITH ADVANCED ORGANOID MODELS. - PARKINSONâS DISEASE (PD) IS THE SECOND MOST COMMON NEURODEGENERATIVE CONDITION, WITH SERIOUS NEGATIVE IMPACTS ON QUALITY OF LIFE, AS WELL AS FINANCIAL AND PERSONAL BURDEN ON SUFFERERS AND CAREGIVERS. THERE REMAINS NO DISEASE MODIFYING THERAPY. PD IS STRONGLY LINKED TO ABERRANT OLIGOMERIZATION AND ACCUMULATION OF ALPHA-SYNUCLEIN (ÎSYN) PROTEIN. MESENCHYMAL STEM CELLS (MSCS) ARE MULTIPOTENT CELLS THAT CAN BE ISOLATED FROM VASCULARIZED TISSUE THROUGHOUT THE BODY AND EXERT REGENERATIVE EFFECTS THROUGH THEIR DYNAMIC SECRETOME, WHICH IS INFLUENCED BY MULTIPLE FACTORS INCLUDING THEIR MICROENVIRONMENT AND ANY SURROUNDING PATHOLOGY. IN THIS PROPOSAL, WE HYPOTHESIZE THAT BY CONDITIONING MSCS WITH PD-SIMULATING STIMULI, BOTH CHEMICAL AND PATIENT-DERIVED, WE WILL ENRICH THEIR SECRETOME FOR FACTORS WHICH ARE PARTICULARLY BENEFICIAL IN COMBATING ÎSYN-ASSOCIATED PATHOLOGY. THE POTENCY OF CONDITIONED MSCS IN TARGETING ÎSYN PATHOLOGY WILL BE ASSESSED USING BIOCHEMICAL AND STAINING METHODS, USING PROTEIN COMPLEMENTATION, SEMI-NATIVE WESTERN BLOT AND IMMUNOHISTOCHEMICAL ANALYSIS OF OLIGOMERIC ÎSYN IN CELLULAR MODELS OF SYNUCLEINOPATHY, AS WELL AS ASSESSING TOXICITY. BY COMPARATIVE PROTEOMIC ANALYSIS OF THE MSC SECRETOME IN THE PRESENCE AND ABSENCE OF PD-SIMULATING STIMULI WE WILL IDENTIFY THESE BENEFICIAL SECRETED MOLECULES AND VALIDATE THEM FOR EFFICACY IN ALLEVIATING ÎSYN-ASSOCIATED PATHOLOGY IN CELLULAR MODELS OF SYNUCLEINOPATHY. FOR THE K00 PORTION OF THIS PROPOSAL, FOCUS SHIFTS TO ALZHEIMERâS DISEASE (AD), AN EVEN MORE COMMON NEURODEGENERATIVE CONDITION WITH NO MEANINGFUL THERAPEUTIC INTERVENTIONS. CLINICAL TRIALS BASED ON RODENT STUDIES FAIL TO TRANSLATE EFFICACY TO HUMAN SUBJECTS, HIGHLIGHTING THE NEED FOR PHYSIOLOGICALLY RELEVANT TRANSLATABLE MODELS. FURTHER, GENETIC ASSOCIATION STUDIES HAVE HIGHLIGHTED MORE THAN 20 RISK LOCI, USUALLY RELATIVELY COMMON BUT WITH MODERATE