The Development of an Astrocyte Hemichannel Blocker to Delay Spatial and Temporal Progression in ALS
Abstract
The mechanisms by which disease progresses in ALS, both anatomically and temporally, is unknown. Halting or slowing disease progression after onset, when patients are typically diagnosed, would offer enormous practical therapeutic potential. A consistent theme in our understanding of disease progression, after onset, in ALS suggests that astrocytes play a role in this progression. Our most recent work, implicates the astrocyte connexin, Cx43, as a mediator of MN toxicity using in vitro mouse ALS modeling. We hypothesize that the network of astrocytic hemichannels (HC), composed of connexin 43, may modulate the spatial and temporal progression of disease which ultimately results in MN death or dysfunction. Therefore, modulating Cx43 HC may be an excellent target for an ALS therapeutic. Tonabersat is a drug that has been shown to block Cx43 hemichannels in several studies and this hypothesis provides the foundation for this program. We will use human induced pluripotent stem cells from ALS patients along with animal models of ALS to study Cx43 HC mediated toxicity in ALS and to examine the ability of Cx43 HC blockers to block neurotoxicity in these models.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1194710
Entities
People
- Nicholas J Maragakis
Organizations
- Johns Hopkins University