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Once Weekly Dosing GLP-1 Promotes Beta-Cell Growth

Posted: Saturday, June 30, 2007

Preclinical data suggests a long-acting formulation of native, human GLP-1 can promote the growth of insulin producing cells (beta cells) in a type 1 diabetes animal model. 
Sandra Reichstetter, PhD, a company scientist at PharmaIn, Ltd. announced last Saturday during her oral presentation at the ADA Sessions,  data from preclinical animal experiments supporting use of PGC GLP-1, a nanocarrier-based formulation of native, human GLP-1 (glucagon-like peptide 1), to potentially treat type 1 diabetes. 

“We are very excited about our data,” said Sandra Reichstetter, PhD, principle author and research scientist at PharmaIN.  “We were able to show that our technology improves the pharmacokinetics of native human GLP-1 and enables it to accumulate in the inflamed pancreas.  Importantly, we also showed improved blood glucose control and overall health in STZ treated rats using a very low dose of PGC GLP-1.”

High-dose streptozytocin treated rats, an experimental animal model for type 1 diabetes, were dosed with formulated human GLP-1 (PGC GLP-1), unformulated GLP-1, or control vehicle alone.  The group treated with PGC GLP-1 showed evidence of improved glucose control and weight gain as compared to control animals – suggesting improved beta cell activity.  The company was recently awarded a $3 million grant from NIH/NIDDK to support development of PGC GLP-1 to treat type 1 diabetes.

“I believe we are on the cusp of developing breakthrough therapies for type 1 diabetes patients” said William Hagopian, MD, PhD, Principal Investigator, Pacific Northwest Research Institute and Clinical Associate Professor of Medicine at the University of Washington School of Medicine.  “One potential breakthrough would be our ability to regenerate beta cells in type 1 diabetic patients, perhaps even in late disease stages long after diagnosis.  The approach offers a solid start to this beta cell regeneration effort by enabling steady delivery of human GLP-1.  Steady levels mean higher concentrations can be delivered with less toxicity, which is a significant advance.  I believe that human GLP-1 in combination with other islet growth factors has a good chance of success in islet regeneration, with the potential to dramatically change how we deal with type 1 diabetes.  The PharmaIN formulation might also be able to increase GLP-1 targeting directly to the sites of inflammation in the prediabetic stages of type 1 diabetes, potentially rendering new and existing beta cells more resistant to immune attack.”

PGC GLP-1 is a novel formulation of the native (natural form) human sequence peptide GLP-1 (glucagon-like peptide 1) using the Company’s proprietary drug delivery technology, PGC™ (Protected Graft Copolymer).  The formulation is expected to be dosed weekly by patients.  The PGC technology increases the half-life of native GLP-1 hundreds-fold while maintaining natural biological activity of the peptide.  PGC GLP-1 is in late stage preclinical testing for the treatment of type 1 and type 2 diabetes.  PGC GLP-1 has the potential to treat a number of conditions, including diabetes, obesity, certain cardiovascular conditions, and medical conditions where patients need improved glycemic control.

PGC GLP-1 is part of the new therapeutic class called “incretins”.  This class includes natural human incretins, non-human incretin analogs and incretin mimetics, drugs all intended to improve insulin secretion in patients.  The natural sequence human incretin GLP-1 is secreted by the gastrointestinal tract in response to food intake.  GLP-1 acts as an incretin to lower blood glucose via stimulation of glucose-dependent insulin secretion and insulin production from islet beta cells. GLP-1 also exerts actions independent of insulin secretion, including inhibition of gastric (stomach) emptying and acid secretion, reduction in food ingestion and glucagon (a hormone important in increasing levels of glucose in the blood) secretion, and stimulation of beta cell proliferation (1).  Beta cells are the cells responsible for insulin production.

Source: Diabetes In Control: The data wase presented in an Oral Session at the ADA meeting entitled: Incretin Based Therapies – Today and Tomorrow, Monday, June 25, 2007 presentation number 0282-OR “Long-Acting GLP-1 for the Treatment of Type I Diabetes”.

 
 
 
 
 
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