Formulations to Prevent Neurological Diseases and Disorders, including TBI

Traumatic brain injury (TBI) is a major source of death and long-term physical, cognitive and mental disability worldwide, with roughly 27 million new cases each year. In the U.S. alone, this results in almost 70,000 deaths, annually. Although TBIs can affect people of all ages, the risk of getting a TBI is greatest in adolescents, young adults and people over the age of 75. TBI also has a higher prevalence among military personnel, athletes and people in correctional or detention facilities. Because the demographic at greatest risk can be identified, prevention strategies for these demographics, are needed to reduce the risk of long-term disability.  
 
Researchers at Arizona State University have developed a novel nervous-system specific formulation to elicit antigen-specific, anti-inflammatory responses and modulate the activity of peripheral immune cells to reduce symptoms of neurological diseases, disorders, and trauma, including TBI. This formulation utilizes a particle comprising poly(alpha-ketoglutarate) (paKG), a glycolysis pathway inhibitor, and at least one of a proteolipid protein (PLP), PLP antigen, myelin oligodendrocyte glycoprotein (MOG), MOG peptide, myelin-associated glycoprotein (MAG), or MAG peptide, to generate immunosuppressive cell phenotypes. When tested in a CCI mouse model, the results suggest that the formulation increased migratory macrophages within this population, decreased inflammatory markers in dendritic cells (DCs) and macrophages, and increased suppressive markers in the migratory macrophage population.
 
This formulation represents a novel breakthrough for modulating the peripheral immune system to change the phenotype of brain-resident microglial cells, which could be utilized as a preventative for reducing the chronic inflammatory symptoms associated with neurological diseases, disorders and trauma.
 
Potential Applications
  • Formulation to prevent inflammatory symptoms associated with neurological diseases, disorders, and trauma:
    • TBI, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, etc.
Benefits and Advantages
  • The formulation can be utilized to modulate the innate immune responses systemically
    • Gives rise to changes in the adaptive immune system and leads to infiltration of both innate and adaptive immune cells into the brain
  • Only mice treated with the formulation were able to significantly increase the frequency of Tregs in the brain
    • Within this Treg population the formulation significantly increased the frequency of immunosuppressive PLP-specific central memory T cells
  • A significant decrease in the frequency of proliferating PLP-specific T helper type 1 cells was observed
    • These cells, in an antigen-specific manner, might induce inflammation by secreting pro-inflammatory cytokines
  • Enhances anti-inflammatory innate immune responses in the brain
    • Lower expression of inflammatory markers CD80 & CD86 within the migratory DC population
    • Infiltrating macrophages had lower expression of MHCII
 
For more information about the inventor(s) and their research, please see
 
Patent Information:
Direct Link:
https://canberra-ip.technologypublisher.com/tech?title=Formulations_to_Preven t_Neurological_Diseases_and_Disorders%2c_including_TBI
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For Information, Contact:
Jovan Heusser
Director of Licensing and Business Development
Skysong Innovations
jovan.heusser@skysonginnovations.com