Repurposing of DPP-4 Inhibitors
Solid organ and hematopoietic stem cell transplantation are life-saving procedures but remain limited by alloimmune complications such as acute and chronic graft-versus-host disease (GVHD) and solid organ rejection. Despite progress in immunosuppressive regimens, outcomes remain suboptimal due to drug toxicities, infections, and refractory disease states.
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Dipeptidyl peptidase-4 (DPP-4) inhibitors, approved for type 2 diabetes, have emerging immunomodulatory roles through their effects on T-cell activation, trafficking, and cytokine production. Notably, DPP-4 (CD26) is expressed on activated T cells and is implicated in key immune processes relevant to graft rejection and GVHD.
Inventors
Dr. Moshe Yeshurun, Rabin Medical Center
Contact info
Sari Prutchi Sagiv PhD Director of Pharma and Diagnostics
For further information please contact:
sari@mor-research.comSteroid-refractory acute GVHD (SR-aGVHD) and chronic GVHD (cGVHD) have limited effective, durable treatment options.
Solid organ transplant rejection, especially in high-risk patients, still compromises long-term graft function and survival.
Existing immunosuppressive agents carry high toxicity burdens and are often poorly tolerated long-term.
No DPP-4 inhibitors are currently approved for immunomodulatory indications in transplant medicine.
We propose the use of high-dose DPP-4 inhibitors (such as sitagliptin and linagliptin) as oral, low-toxicity immunomodulatory agents to:
1. Prevent acute and chronic allograft rejection in solid organ transplant recipients.
2. Treat SR-aGVHD and moderate-to-severe cGVHD, leveraging their effects on effector T-cell suppression and Treg enhancement.
3. Serve as steroid-sparing or calcineurin-sparing agents, reducing toxicity from traditional therapies.
GVHD affects ~30-50% of allogeneic hematopoietic stem cell transplant recipients; the steroid-refractory segment is a significant high-value, unmet-need subpopulation.
Solid organ transplantation exceeds 150,000 procedures annually worldwide, with a multi-billion-dollar immunosuppression market.
Repurposing an existing drug class with well-known safety profiles can dramatically reduce development costs and timelines, while addressing high-risk, underserved populations.
POC in patients with GVHD with promising results
Provisional patent submitted Nov 2025