Stimulation of Dendrite Growth and Spine Formation by Norrin and LGR6: A Target for Therapy in CNS Injury and Degeneration

Unmet Need
Astroglial dysfunction is associated with the development of numerous central nervous system (CNS) diseases, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Huntington’s disease (HD). Astroglia are the homeostatic cells of the central nervous system and play key roles in the development and support of neuronal networks. Astroglia have historically been categorized into two subtypes: protoplasmic and fibrous astroglia. However, recent research has demonstrated that astroglial populations are more heterogeneous and that altered function in a subset of astroglia could exacerbate disease pathogenesis. Consequently, the identification of novel therapeutic targets within subsets of astroglia that contribute to disease progression could improve the treatment options for CNS injury. 
 
Technology Overview
The inventors have identified a critical subset of adult cortical astroglia, called the 8.3-astroglia. This subset represents approximately 28% of all cortical astroglia. The inventors found that the 8.3-astroglia selectively secretes Norrin and LGR6. These inventors found that these two protein pathways are key for function of 8.3-astroglia and are abrogated in ALS rodent models and human ALS. Due to the importance of these pathways in the regulation of cortical neuron dendritic growth and neuronal spine formation, they are a promising therapeutic target for the treatment of numerous CNS diseases, including brain injury, dementia, developmental diseases, neurological diseases, and neuronal injury.
 
Stage of Development
The inventors have demonstrated that Norrin and LGR6 are abrogated in ALS rodent models and human ALS.
 

Category(s):