Endoplasmic reticulum stress relievers for increasing the production of insulin in beta cells

This technology is a stress reliever for the endoplasmic reticulum (ER) that can improve beta cell function and survival as a potential treatment for diabetes.

Unmet Need: Small molecule treatment for beta cell disorders related to diabetes

Currently, most treatments for diabetes rely on enhancing insulin production by beta cells, reducing production of glucose by the liver, or increasing glucose excretion. Accumulating evidence suggests that ER stress plays a role in the pathogenesis of beta cell functional derangements and demise in diabetes. However, there are currently no available explicit therapeutics to reduce ER stress.

The Technology: Small molecule treatment to prevent and reverse stress-related beta cell degradation in diabetes and diseases

This technology consists of small molecules that are capable of relieving ER stress, leading to increased insulin production in beta cells, improved insulin secretion and possibly enhanced beta cell survival. Tauroursodeoxychlic Acid (TUDCA) and 4-phenylbutyric Acid (PBA) are two compounds capable of reducing ER stress. TUDCA and PBA exhibit low toxicity and effectively aid in preserving beta cell mass by protecting the cell from harmful effects of inflammatory and metabolic stress. As such, this technology provides a targeted potential treatment for diabetes that helps to preserve the patient’s own beta cells.

This technology has been validated using Wolfram syndrome patient-derived stem cells and beta-like insulin-producing cells.

Applications:

• Prevention of beta cell loss in diabetic patients through relief of ER stress
• Early stage treatment option to prevent onset of type I and II diabetes prior to clinical symptoms
• Treatment of Wolfram syndrome
• Use in treatment of Wolcott-Rallison syndrome
• Treatment of permanent neonatal diabetes
• Utilization in research studying ER stress as a recovery assay
• As part of combination therapy in diabetes management

Advantages:

• Treats beta cell deterioration
• Can prevent diabetes progression
• Can be applied to other disorders and conditions involving ER stress related beta cell death
• Has potential in diseases associated with ER stress in other cell types
• Can act in synergy with other therapies required to manage diabetes

Lead Inventors:

Rudolph L. Leibel, M.D., Dieter Egli, Ph. D., Robin Goland, M.D.

Patent Information:

Patent Status

Related Publications:

• Shang L, Hua H, Foo K, Martinez H, Watanabe K, Zimmer M, Kahler DJ, Freeby M, Chung W, LeDuc C, Goland R Leibel RL, Egli D. “Beta cell dysfunction due to increased ER stress in a stem cell model of Wolfram syndrome” Diabetes. 2013 Nov 8; 63(3): 923-33.

Tech Ventures Reference:

• IR CU12150

• Licensing Contact: Ron Katz