Siglitin targets the two peptide peptide enzyme-4 (DPP-4), which is involved in a variety of processes in the body.
in the treatment of type 2 diabetes, sigletin improves insulin secretion and controls blood sugar.
Hal Broxmeyer of Indiana University, one of the co-authors of the study, is an expert in cord blood stem cell transplantation.
he had found in previous studies that DEP-4 regulates blood cell production, so he explores whether taking siglitin could improve the implantation of cord blood transplants.
unexpected result was that preliminary data showed that the rate of GVHD in patients was much lower than expected, and that Sigredine targeted DEP-4 to inhibit immune T cell activation leading to GVHD.
in this clinical study, 36 hematopoietic stem cell transplant patients were orally treated with sigletin. The patients in
study were aged 18-60 years and had one of the following blood disorders: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), or myeloid growth syndrome (MDS).
the day before the transplant, on the day of the transplant, plus 14 days after the transplant, oral sigletin.
36 patients, only 2 had an acute GVHD- 5% rate within 100 days of transplantation, which meant a significant decrease in the GVHD rate.
previous studies showed that 34-51% of patients were affected by GVHD in the first three months of the transplant.
patients did not show any unexpected or abnormal toxic reactions or higher recurrence rates after transplantation.
"This is a drug used to treat diabetes, and we are using it at a higher dose."
"We looked at whether this led to hypoglycemia, and we haven't found that yet," said study lead author Sherif Farag of Indiana University.
Sherif Farag said Siglutin's "new use of old drugs" provided a relatively inexpensive and readable way to prevent GVHD.
these findings are very significant because there are many other different drugs being tested, including those that are more expensive or require long intravenous administration," he said.
this provides new methods and targets for preventing GVHD.
GVHD in this trial was much lower than we expected.
" the findings will require larger, multi-center randomized studies to further confirm them.
team also hopes to explore whether a combination therapy that includes Sigretin can prevent chronic graft anti-host disease.
resources: iU research findings can reduce treatment-related complications for blood cancer patients. Retrieved 2021-01-11, from [2] Sherif S. Farag, et al., (2021). Dipeptidyl Peptidase 4 Inhibition for Prophylaxis of Acute Graft-versus-Host Disease. N Engl J Med,DOI: 10.1056/NEJMoa2027372
