The Need

Systemic lupus erythematosus (SLE) is an orphan disease affecting approximately 5 in every 10,000 individuals. Despite its rare prevalence, this lifelong autoimmune disease has few effective targeted therapies. Current treatments are palliative using anti-inflammatory drugs or broad spectrum immunosuppression. Although such treatments are acutely effective, long term use can result in undesireable side effects, including fatigue, anemia, cardiovascular disease, and others. Accordingly, there is a high unmet need for more effective, targeted SLE treatment options.

The Technology

Researchers at The Ohio State University led by Dr. Wael Jarjour, a senior professor of Rheumatology and Immunology, has developed a therapeutic cocktail to reduce the inflammatory response in SLE. The cocktail comprises locked nucleic acids (LNAs) that act as microRNA(miR) antagonists targeting miR-21, miR-29a, and miR-29b. These miRs are upregulated, packaged, and secreted within bioactive extracellular vesicles in SLE and induce inflammation via toll-like receptors (TLR)7/8. LNAs are synthetic RNA molecules with a chemically modified backbone, which translates to in vivo stability for over 2 weeks – a significant improvement over current miR-derived therapies. Evaluation of this novel inhibitory cocktail in a humanized murine model of SLE demonstrated a reduction of numerous indicators of systemic inflammation, including a reduction of circulating adaptive immune cells, serum IL-1β, IL-6, IL-8 IL-10, and TNF-α. Importantly treatment with the anti-miR cocktail reduced histopathological inflammation in the small intestine, liver, and kidney. Collectively, Dr. Jarjour's studies suggests the novel LNA cocktail may be an effective therapeutic candidate for the treatment of SLE.

Benefits/Advantages

• Suppresses inflammatory histopathology in multiple organs affected by the disease, including the primary target of inflammation in lupus nephritis (kidneys)
• LNAs are physiologically stable in vivo with bioactive capacity significantly longer than current miR-based therapeutics, potentially reducing the dosing regimen for patients and enhancing efficacy
• Unlike other miR-based therapeutics, LNA-derived therapeutics do not require delivery mechanisms to prevent extracellular degradation in vivo

Commercial Applications

• Systemic Lupus Erythematosus
• Lupus Nephritis

Intellectual Property

• U.S. Patent Application No. 16/645,656