Repurposing a Kinase Inhibitor to Regenerate Insulin-Producing Cells in Type 2 Diabetes

This invention is a method of treating type 2 diabetes by orally administering the focal adhesion kinase (FAK) inhibitor PF-562271, which increases the number of insulin-producing beta cells. In a preclinical diabetes model, a short course of treatment normalized blood glucose in most animals, and glucose remained normal for a month after dosing stopped.

Description

Type 2 diabetes involves insufficient insulin function, and restoring functional beta cell mass is a central goal of treatment. This technology uses PF-562271, a small-molecule inhibitor of focal adhesion kinase, an enzyme involved in cell adhesion and migration. In treated mice, the inhibitor drove pancreatic acinar cells, which normally make digestive enzymes, to convert into insulin-producing beta cells.

These acinar-derived cells stopped expressing the digestive enzyme amylase and moved into the existing islets of Langerhans, the pancreatic clusters that regulate blood sugar. There they sit near blood vessels and express Glut2, a glucose-sensing feature of mature beta cells. Cell-tracing experiments confirmed that the new insulin-producing cells originated from acinar cells. Genetic deletion of FAK in the pancreas produced the same acinar-to-beta-cell shift, supporting the mechanism. The therapy is given by mouth, and treatment can be monitored through beta cell function, glucose tolerance, plasma glucose and insulin levels, and HbA1c.

Applications

- Oral therapeutic for the treatment of type 2 diabetes
- Beta cell regeneration therapy aimed at restoring endogenous insulin production
- Short-course treatment regimen that does not require continuous dosing once blood glucose is normalized
- Drug-repurposing programs for an agent already evaluated in humans in another disease area
- Companion monitoring approaches that detect acinar-derived beta cells during therapy

Advantages

- Converts acinar cells into insulin-producing beta cells that embed in the islets of Langerhans
- Lowers plasma glucose and raises plasma insulin levels
- Blood glucose remained normalized one month after treatment ceased, indicating the effect does not depend on continuous dosing
- Oral small-molecule delivery, given once or twice daily
- Works as a stand-alone treatment, with no other diabetes medication required

Invention Readiness

In vivo and Phase-1 dose escalation trial data

IP Status

https://patents.google.com/patent/US12702667B2

Related Publication(s)

Dahiya, S., Saleh, M., Rodriguez, U.A. et al. Acinar to β-like cell conversion through inhibition of focal adhesion kinase. Nat Commun 15, 3740 (2024). https://doi.org/10.1038/s41467-024-47972-4