Transplantation of Pluripotent Stem Cell Derived Microglia for the Treatment of Adult-onset Leukoencephalopathy (HDLS/ALSP)
Grant Award Details
Grant Type:
Grant Number:
DISC2-12130
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$214,668
Status:
Closed
Progress Reports
Reporting Period:
Year 1
Grant Application Details
Application Title:
Transplantation of Pluripotent Stem Cell Derived Microglia for the Treatment of Adult-onset Leukoencephalopathy (HDLS/ALSP)
Public Abstract:
Research Objective
We propose to investigate the transplantation of pluripotent stem cell derived microglia as a potential therapy for the devastating neurological disease; Adult-onset leukoencephalopathy (ALSP/HDLS).
Impact
The most immediately impacted condition will be ALSP. However, further examination of the safety of human microglial transplantation will have broad implications for many neurodegenerative disorders
Major Proposed Activities
We propose to investigate the transplantation of pluripotent stem cell derived microglia as a potential therapy for the devastating neurological disease; Adult-onset leukoencephalopathy (ALSP/HDLS).
Impact
The most immediately impacted condition will be ALSP. However, further examination of the safety of human microglial transplantation will have broad implications for many neurodegenerative disorders
Major Proposed Activities
- We will differentiate the human embryonic stem cells line ESI-017 into micoglia, the primary immune cell of the brain.
- We will assess the purity of stem cell derived microglia by examining multiple markers for microglia and stem cells. We aim to achieve greater than 99% purity.
- We will utilize single cell RNA sequencing as a sensitive method to determine whether any contaminating pluripotent stem cells remain following microglial differentiation.
- Using specialized mice that develop ALSP pathology and allow human cells to be transplanted, we will engraft human microglia into the brain.
- We will allow mice to age for 3 months and then use a series of tests to examine the impact of micorglial transplantation on motor and cognitive function.
- We will examine the impact of human microglial transplantation on ALSP-associated neuropathologies. We will then report our results and schedule a discussion with the FDA.
Statement of Benefit to California:
Adult-onset leukoencephalopathy (ALSP) is a neurological disease that effects patients during the prime of their lives. Although rare, ALSP represents the clearest example of a ‘microgliopathy’, a disorder that affects microglia, the immune cell of the brain. As microglial dysfunction is implicated in virtually all neurological disorders, the examination of stem cell-derived microglia to treat ALSP could provide important insight into many of the neurological diseases that affect Californians.