Use of 2-Hydroxyoleic Acid for the Treatment of Systemic Lupus Erythematosus and Other Immune Pathologies

A novel B cell tolerance pathway activated by the lipid enzyme sphingomyelin synthases 2 (SMS2). 
  Background:
Autoimmune diseases such as Systemic Lupus Erythematosus are chronic, painful and debilitating. The Lupus Foundation of America estimates that 1.5 million Americans, and at least five million people worldwide, have some form of lupus. The vast majority of those are women of color. About 10 percent of people with lupus will die prematurely of their disease, but the rest will have it impact their quality of life significantly. About 20 percent of those with a work disability have it due to lupus-related symptoms.
Medicare patients diagnosed with lupus have an average of twice the physician visits, ER visits, and hospitalizations as those without lupus. This increased care represents over $10K per year in direct health care costs for each lupus patient with Medicare. SLE is a multisystem autoimmune disease. Diseased autoantibodies Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease. Circulating autoantibodies, by their circulating nature, are responsible for the heterogeneous presentation of this disease, which targets a variety of organs, causing different clinical pictures. Antinuclear antibodies are the hallmark serological feature of SLE, and anti-double stranded DNA antibodies are so commonly observed that they serve as a widely recognized biomarker of SLE disease activity.
  B cell tolerance normally prevents autoimmunity by deleting or deactivating autoreactive B cells capable of causing autoantibody-driven disorders.
When that mechanism malfunctions, autoantibody-secreting plasma cells are neither deleted nor deactivated, and an autoimmune disorder results.
  A method to improve elimination of these autoreactive B cells by enhancing self-protective B cell tolerance mechanisms in the Germinal Center would be an effective therapeutic strategy for treating SLE.
  Improvements in diagnosis and therapy have nearly doubled the 5-year survival rate for lupus patients, but the immunosuppressive drugs used to treat lupus have significant side effects. As with all autoimmune diseases, there is still no cure. Understanding the mechanism on a molecular level and using that information to develop more effective and less toxic therapies is a critical next step on the way to finding a cure. Technology Overview: Researchers at SUNY Downstate have identified a novel B cell tolerance pathway activated by the lipid enzyme sphingomyelin synthases 2 (SMS2). SMS2 deficiency impairs the activation of protein kinase C-delta (PKCδ), whose genetic deficiency causes lupus-like disease in both humans and mice. SMS2 is required for nuclear PKCδ translocation, a key lupus-associated apoptotic process.
  RNA sequencing showed that patients with lupus had substantially reduced SMS2 expression in B cells and had near absent SMS2 in their expanded autoimmune-prone, age-associated B cells (ABCs), but healthy individuals did not. They have proposed a novel therapeutic approach that selectively inhibits autoantibody production via the enforcement of GC B cell tolerance by targeting and activating SMS2 with a known non-toxic SMS activator, 2-hydroxyoleic acid (2OHOA). 2-hydroxyoleic acid helps the body reduce the levels of autoantibodies. This drug may be given alone, or in tandem with either an immunosuppressor, a corticosteroid, and NSAID, and anti-malarial, or other. Further Details:

https://suny.technologypublisher.com/files/sites/adobestock_419089868.jpeg Intellectual Property Summary:  
– WO/2019/099664
– Provisional patent
– Patent application submitted Licensing Status:
This technology is available for licensing.
This technology is available for licensing.

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