Nanoparticle delivery of insulin gene to fight juvenile diabetes developed

A safer method to deliver the insulin gene to diabetes patients using nanoparticles, was presented at the 10th Annual Meeting of the American Society of Gene Therapy (ASGT) in Seattle.

Type 1 or juvenile diabetes is caused by autoimmune destruction of the insulin producing pancreatic ß-cells. As a result of the loss of insulin, blood sugar levels rise too high, causing damage to fine blood vessels and nerve endings leading to debilitating symptoms. As a result patients become dependent upon daily insulin injections to survive. However, it is virtually impossible to match the sugar content of each meal with the optimal dose of insulin – the cumulative ‘mistakes' severely reduce both the quality and length of life.

Recreating appropriately regulated internal insulin secretion in surrogate cells (i.e. non-ß-cells) in individuals with diabetes is an attractive approach to cure this disease. A major hurdle with this approach has been replicating automatic insulin secretion that is tuned to the body's requirements.

Dr. Anthony Cheung and his colleagues at enGene, Inc., Vancouver, aim to develop an approach to restore the meal-responsive insulin production and release capability in individuals with diabetes, thereby eliminating the need for insulin injections while also improving control of blood sugar levels.

They intend to achieve this by inducing specific cells of the gut to take over production of insulin. The team previously reported that gut K-cells can be induced with the insulin gene to produce insulin in response to meal ingestion in a pattern comparable to normal insulin production from the pancreas.

In order to translate this technology to clinical use, the team developed a novel method to deliver the insulin gene to the target K-cells in the gut using nanoparticles. The nanoparticles contain a component called chitosan that provides protection to the insulin gene while in the gut as well as an integrase to insert the insulin gene into the patient's gut cells.

Gene delivery by these nanoparticles is expected to be safer and less immunogenic than more commonly used virus-based agents. In the preclinical testing reported in this conference, a single administration of the nanoparticles induced the production of insulin in the recipients for over 130 days. Moreover, the insulin production was responsive to meals.

Work is currently underway to support an Investigational New Drug filing with the FDA, anticipated by late 2008 or early 2009, after which the team plans to test these nanoparticles in individuals suffering from diabetes.

The American Society of Gene Therapy is a professional non-profit medical and scientific organization dedicated to the understanding, development and application of gene and related cell and nucleic acid therapies and the promotion of professional and public education in the field. For more information, visit

http://www.asgt.org

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