Super Active Leptin Antagonists for Treatment of Autoimmune Diseases and CKD-associated Cachexia
Innovative Products and Technologies
Technology Offer
Super Active Leptin Antagonists for Treatment of Autoimmune Diseases and CKD-associated Cachexia
- Yissum - Research Development Company of the Hebrew University
- From Israel
- Responsive
- Innovative Products and Technologies
Summary of the technology
Cluster8
A novel Recombinant leptin mutant acts as antagonist has a strong potential for pharmacologic agent for autoimmune and inflammatory diseases, cancers, and cardiovascular disease, among others. Substitution of two to four amino acid residues of leptin to alanine converts agonist to antagonist without reducing affinity toward leptin receptor.
Keywords: Leptin, antagonist, mutein, multiple sclerosis, inflammatory bowel syndrome, rheumatoid arthritis, fibrosis, cardiovascular disease, breast cancer, colon cancer, prostate cancer, ovarian cancer, obesity
Project ID : 8-2006-198
Details of the Technology Offer
Categories Superactive High Afinity Leptin antagonist, mutein, multiple sclerosis, inflammatory bowel syndrome, rheumatoid arthritis, fibrosis, cardiovascular disease, CKD Cachexia, Osteoarthritis Development Stage (1) In vivo tests in animal (mouse) models, (2) Preparation of second generation of antagonists with increased affinity toward leptin receptor and longer in vivo persistence in circulation Patent Status Patent number application: WO2011/132189A3
Highlights
- Advances treatment of many diseases by blocking undesired leptin effects
- Interacts with mammalian leptin receptor with affinity identical to non-mutated leptins
- Can be easily prepared in large quantities as recombinant protein expressed in E. coli
- Effectiveness established in three mice models of human acute and chronic fibrosis
Our Innovation
- Recombinant leptin mutein acts as antagonist
- Isolated DNA molecule encoding super active leptin antagonist
- Strong potential for pharmacologic agent for CKD (Chronic Kidney Disease) associated cachexia, autoimmune and inflammatory diseases, cancers, and cardiovascular disease, among others
- Substitution of two to four amino acid residues of leptin to alanine converts agonist to antagonist without reducing affinity toward leptin receptor
The Opportunity
- Addresses multiple markets for treatment of multiple disease entities, specifically, CKD associated cachexia
- Expands various research fields stressing proteins that inhibit leptin activity
Development Milestones
- Testing super activeleptin antagonist activity in additional in vivo models e.g., Cachexia Inflammatory Bowel Disease in mice or others
- Preparation of leptin antagonists with more potent activity in vivo
Additional Information
- A. Gertler. Development of leptin antagonists and their potential use in experimental biology and medicine. Review. Trends in Endcrinol. Metab. 17: 372-8 (2006).
- Elinav E, Ali M, Bruck R, Brazowski E, Phillips A, Shapira Y, Katz M, Solomon G, Halpern Z, Gertler A.Competitive inhibition of leptin signaling results in amelioration of liver fibrosis through modulation of stellate cell function. Hepatology 49:278-86 (2009)
- Shpilman M, Niv-Spector L, Katz M, Varol C, Solomon G, Ayalon-Soffer M, Boder E, Halpern Z, Elinav E, Gertler A.Development and characterization of high affinity leptins and leptin antagonists. J Biol Chem. 286:4429-42 (2011).
- Gertler A, Elinav E.Novel superactive leptin antagonists and their potential therapeutic applications. Curr Pharm Des. 20:659-65 (2014)
- W.W. Cheung et. al A Pegylated Leptin Antagonist Ameliorates CKD-Associated Cachexia in Mice. J. Am. Soc. Nephrol 25:119-282 (2014).