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exsulin discovery and development

In the search for an endogenous agent that could stimulate islet regeneration, Dr. Lawrence Rosenberg showed that a protein extract prepared from partially duct obstructed pancreata and administered to hamsters increased endocrine cells budding from ducts (Rosenberg, Diabetologia 1996). From this pancreatic extract, Dr. Rosenberg, Dr. Arthur Vinik at Eastern Virginia Medical School, and their colleagues isolated and identified the agent responsible for regeneration activity and named it islet neogenesis associated protein (INGAP) (Rafaeloff et al., J Clin Invest 1997). INGAP peptide was then identified as the 15 amino acid sequence within INGAP, which carries the regeneration activity and is a suitable candidate for therapeutic development. INGAP Peptide—now branded as Exsulin—has been tested in various T1DM animal models, including STZ-treated mouse, the BB rat and the NOD mouse. Toxicology testing was done in dogs and monkeys, and in both of these toxicology studies, evidence of regeneration activity was also noted. INGAP Peptide has also shown evidence of stimulating regeneration in the in vitro human islet derived system and demonstrated evidence of restoring insulin secretion and improving glycemic control in people with Type 1 and Type 2 diabetes.

support for exsulin as a regeneration therapy

Evidence for exsulin’s islet regeneration activity and promise as a therapeutic is
found in four categories:

• Human islet derived tissue—INGAP peptide induces formation of islets
that produce insulin.

• Human Patients—previous phase 2 trials showed evidence of neogenesis and improved glycemic control. Phase 2 study results were completed and will be published soon.

• Animal models of diabetes (STZ-treated and NOD mice, hamster, sucrose fed rat)—INGAP peptide has reversed hyperglycemia and increased survival

• Normal animals (dogs, monkeys) in toxicology studies—INGAP peptide treatment was associated with characteristic histology of new islet formation.

the role of exsulin regeneration therapy

The common thread between both major forms of diabetes is insulin deficiency. To cure both forms will require a means of restoring normal insulin secretion and the most feasible approach appears to involve islet regeneration. Glycemic control in both T1 and T2DM patients require combinations of therapies to achieve optimal results. Likewise, Exsulin therapy will be complemented by agents that control insulin resistance in people with T2DM and agents that control autoimmunity in people with T1DM. Many therapies are now available for controlling insulin resistance and several therapies for controlling autoimmunity are entering late stage trials. Surprisingly, no peptide regeneration therapy is now in active clinical trials of T1DM patients, for which there is great unmet clinical need. Exsulin is aimed at being a part of curing both T1 and T2DM.

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