Method for modulating inflammatory responses

Invention Summary:

Cholesterol is a major component of lipid rafts, which are sphingolipid-enriched planar domains of the cell membrane. Rafts play key roles in a variety of the cell signals processes including calcium entry into cells, which activates white blood cells and causes inflammation. Many inflammatory cell responses are tightly controlled by the regulated entry of Ca 2+ ions into the cells. Because innate immune cells lack voltage-gated calcium channels, their response to G-protein coupled (GPC) mediators depends in a great measure on store-operated calcium entry (SOCE) into the cells. This process is initiated when GPC receptors linked to Gi or Gq, or when receptor tyrosine kinases that couple to phospholipases activate Phospholipase C (PLC). Moreover, human transient receptor protein1 (TRPC1) is associated with lipid raft domains and changes in TRPC1 localization are involved with the regulation of neutrophil(PMN) SOCE. Thus, total “stimulated calcium entry” in native cells is probably the additive result of several processes including store depletion that can initiate Ca 2+ channel gating.

Researchers at Rutgers have discovered novel pathways by which specific lipids interact to modify the structure and function of inflammatory cells. Sphngosine 1-phosphate (SIP) initiated SOCE has been found to be highly dependent upon lipid rafts in PMN. Ca 2+ -entry dependent inflammatory cellular function was inhibited by either inhibition of Sphngosine 1-phosphate (SIP) synthesis or by methyl-b cyclodextrin (MbCD). MbCD could completely blocks calcium entry into the cells, and these effects were reversed by exogenous SIP and cholesterol restoration.

Based on these discoveries, they developed a method for treating an immune-related disorder in a patient comprising administering an agent to the patient for altering the patient’s plasma concentration of free cholesterol. The agent is a non-statin and comprises methyl-b cyclodextrin, lipid-free albumin, or ezetimibe, which is administered in an amount sufficient to modulate the immune-related disorders.

Market Applications:

The invention enables the creation of novel approaches (agents) to the therapy of a wide variety of immune-related disorders. It also includes the administration of the agent in various pharmaceutical dosage forms e.g. tablets capsules, oral liquids, solutions, drops, emulsions, aerosols etc. The immune-related disorder may comprise of a hyperimmune or autoimmune-related disorders such as, systemic inflammation after trauma, injury sepsis, transplant, transplant rejection, and inflammatory bowel disorders, such as, celiac disease, irritable bowel syndrome, Addison’s disease, and Alzheimer’s disease etc.

Advantages:

  • Strong potential to development novel nutritional supplements that are high in cholesterol and lysolipids that contribute to immune cell raft formation and augment the immunity.
  • Nutritional formulas can be created to modulate immunity more directly and without drug use by dietary micronutrient manipulation.

Intellectual Property & Development Status:

United States patent number US7,879,821 granted on February 1, 2011

Rutgers ID: S05-19
Category(s):
Life Sciences
Therapeutics
Contact:
Deborah Perez
Senior Licensing Manager
848-932-4467
deborah.perez@rutgers.edu
Inventors:
Carl Hauser
Keywords:
Autoimmune
Infectious Disease/Immunology