INVESTIGADORES
CHASSEING Norma Alejandra
congresos y reuniones científicas
Título:
Immunomodulatory oligonucleotide IMT504 induces a marked recovery in a type I diabetes animal model .
Autor/es:
MONTANER A; BIANCHI S,; CALVO V, ; CHASSEING NA; LAGO N; LIBERTUN C; LUX-LANTOS V
Lugar:
Rio de Janeiro
Reunión:
Congreso; Meeting of Advanced Technologies and Treatments for Diabetes. ATTD LA2012.; 2012
Institución organizadora:
Sociedad Brasilera de Diabetes
Resumen:
Immunomodulatory oligonucleotides (im-ODNs) are synthetic molecules that stimulate the innate immune system. We have identified a new ODN-family named PyNTTTTGT. Unlike other im-ODNs, its prototype IMT504 promotes tissue repair in experimental models of bone injury, peripheral nerve crush and pancreatic insult by stimulating progenitor cells. Here, we evaluated the effect of IMT504 on a type I diabetes model. Balb/C-mice were daily ip-injected with STZ (40mg/kg) for 5 days. Animals with glycaemia higher or equal 250 mg/dl were daily sc-injected with 20 doses of IMT504 (20mg/kg/dose) and followed for 60-days. A second group were treated as above, but killed after two consecutive decreases in glycaemia (2-5 doses). IMT504 induced a decline in blood glucose in 88% of treated-mice. At day-60 glycaemia (mg/dl) were: Control+Saline: 130+/-20, Control+IMT504: 115+/-28, STZ+Saline: 557+/-49, STZ+IMT504: 278+/-112 (p=0.01). Of note, IMT504 promoted a transient decrease in body weight. Moreover, IMT504-treated animals showed a partial recovery in pancreatic function as measured by GTT, HOMA-B and HOMA-IR. Supporting these findings, the number of islet per pancreatic area was enhanced in STZ+IMT504 vs. STZ+Saline. Also, there was a marked reduction of leukocyte infiltration in and around islets both at 5- or 60-days. Further, cytokine profile at early times showed an increase in IL6 and TNF-alfa in IMT504-treated animals, a fact that could be associated with the release of immunomodulatory proteins IDO and TSG-6 in islets, at the time of progenitor markers expression. Preclinical assays have demonstrated that IMT504 is a very safe drug. Taken together, these results warrant further studies in the route to clinical application.
