In Vivo Protection by Nuclear Import Inhibitor in a Mouse Model of Type 1 Diabetes (cSN-50)

Summary

Type 1 diabetes is a lifelong autoimmune disease that is rising worldwide and affecting over 10 million children, adolescents, and young adults. The current standard of care is lifelong injection of insulin; however, this does not counter the autoimmune attack or eliminate risks for blindness, cardiovascular and renal diseases caused by fluctuating glucose levels. Researchers at Vanderbilt have developed a peptide therapeutic that rendered non-obese diabetic (NOD) mice diabetes-free and insulin-independent for at least one year after only 2 days of treatment at the early stage of disease.

Insulin-dependent Type 1 diabetes (T1D) is a devastating autoimmune disease that destroys beta cells within pancreatic islets. Pioneering stem cell research to replace islet cells does not solve this autoimmune issue. Therefore, new therapies to protect islets from autoimmune destruction and allow continuing insulin production are needed.

Dr. Hawiger and colleagues have developed a first-in-class peptide therapeutic, cSN50 peptide, that affords in vivo islet protection following a 2-day course of intense treatment in non-obese diabetic (NOD) mice, a standard model for T1D. This 2-day treatment resulted in a diabetes-free state for one year without the need for insulin and without apparent side effects (see graph). Additional analysis of these NOD mice indicated that peptide therapy reduced the accumulation of islet-destructive lymphocytes by enhancing activation-induced cell death of T and B lymphocytes. Moreover, pro-inflammatory cytokine and chemokine production in immune cells was attenuated.

These results indicate that this novel form of peptide immunotherapy can arrest destruction of insulin-producing beta cells at the site of autoimmune attack within pancreatic islets. This therapy has potential for use either alone or in concert with other therapies during the progression of T1D. Used alone, cSN50 peptide as a short-term monotherapy has a potential for reversing the ongoing T1D and restore glycemic balance.

- Protects islets from autoimmune attack

- High solubility (100 mg/mL) allows easy delivery

- Reduces inflammation

- Initial studies indicate a plasma half-life of 44hr

- Engineered to cross the plasma membrane

Vanderbilt has both issued and pending patents for this technology. We are seeking either a licensing partner and/or a sponsored research agreement for further development. For additional details, see the PLoS ONE paper published by the Hawiger group on this application.