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Antifreeze glycopeptide improves islet cell transplants for patients with type 1 diabetes
Soaking islet cells in the antifreeze glycopeptide that mimics a naturally occurring glycoprotein found in Arctic fish significantly improves the efficacy of cell transplant treatments for patients with diabetes, according to research in Diabetes.
Researchers found that by soaking islet cells in anti-aging glycopeptide (AAGP, ProtoKinetix) molecules for an hour and washing cells off prior to transplantation, the cells were protected from the antirejection drug tacrolimus.
"Normally when we expose human islets to tacrolimus in the petri dish, they flat line and don't release insulin at all," James Shapiro, MD, PhD, FRCSC, director of the Clinical Islet Transplant Program and Canadian research chair in transplantation, University of Alberta, said in a press release. "When we add the AAGP and wash it all off, the cells work perfectly normally, and are protected in a remarkably durable manner. We find we need far fewer cells to treat diabetes in our preclinical models than we would normally."
Shapiro, who created the Edmonton Protocol in 1999 and has treated more than 250 patients, said most patients typically need two islet infusions prepared from separate pancreas organ donors. However, there aren't enough organ donors to meet demand, Shapiro said.
Through the use of AAGP, more patents could potentially be treated, he said.
"Just a 1-hour soak in AAGP is enough to protect the islet cells for up to a month or two afterwards,” Shapiro said. “It has a very potent and profound effect. As a direct result of these findings, we're now moving forward with plans for a first-in-human clinical trial — led at the University of Alberta — testing this drug in our human islet cell transplant program."
Researchers said the addition of AAGO reduced oxidative stress, enhanced insulin exocytosis, improved apoptosis and also improved engraftment in mice.
"This synthetic molecule seems to provide significant protection to cells exposed to multiple deleterious conditions, such as UV radiation, starvation, extreme temperatures and oxidative stress," Boris Gala-Lopez, PhD, a clinical/research fellow in the department of surgery at the University of Alberta, said in a press release. "We are certainly very excited for the multiple opportunities this finding entails to the field of transplantation research."
Shapiro said AAGP, if successful in human clinical trials, could become a permanent addition to the Edmonton Protocol.
Disclosure: The researchers report that biotechnology company ProtoKinetix, which owns patent rights to the molecule, provided the drug used in this study. One study author reports owning shares in ProtoKinetix.