Grant Award Details

Drug Development of Inhibitors of Inflammation Using Human iPSC-Derived Microglia (hiMG)
Grant Number: 
DISC2-13463
Project Objective: 
  • To use iPSC-derived microglial models to identify and optimize a lead drug candidate targeting the NLRP3 inflammasome, which results from aggregated αSyn and Aβ in forms of Alzheimer’s Disease, Parkinson Disease and other neurodegenerative disorders.
Investigator: 
Type: 
PI
Disease Focus: 
Alzheimer's Disease
Neurological Disorders
Parkinson's Disease
Human Stem Cell Use: 
iPS Cell
Award Value: 
$1,658,123
Status: 
Pre-Active

Grant Application Details

Application Title: 
  • Drug Development of Inhibitors of Inflammation Using Human iPSC-Derived Microglia (hiMG)
Public Abstract: 

Research Objective

We will screen for modifiers of the response to misfolded αSyn and Aβ, and their cognate antibodies. Development of drugs to combat this inflammation is important in neurodegenerative diseases.

Impact

Inhibiting the immune response to minimize NLRP3 inflammasome activation may prevent the neurotoxic effect of activated microglia, and attenuate disease progression in neurodegenerative diseases.

Major Proposed Activities

  • High-throughput Screening: Screen for hit-to-lead compounds that inhibit immune activation triggered by misfolded proteins, monitored by (1) IL-1β reporter line and by (2) ELISA (month 1 - month 6).
  • Efficacy Evaluation of Hits: Evaluate candidate therapeutics in hiMG using misfolded proteins in the presence and absence of their cognate antibodies (month 6 - month 18).
  • Drug Optimization (month 18 - month 24).
  • Further Develop and Complete A Target Product Profile (month 21 - month 24).
Statement of Benefit to California: 

This proposal will benefit citizens of California by developing new treatments for Alzheimer’s disease and Parkinson’s disease based on new anti-inflammatory pathways studied in the innate immune cells of the human brain, represented by hiPSC-derived microglia. These diseases are very prevalent in California, and cause both personal tragedy to families and undue economic burden. Developing a new therapy for these conditions will alleviate this suffering while benefitting the California economy.