Delivering therapies with bio-engineered bacteria

UW-Madison scientists have bio-engineered bacteria to deliver certain therapies to patients with heart disease, obesity, diabetes and other conditions. 

In treating metabolic diseases like these, doctors will often rely on polypeptides as therapeutic agents. They include hormones, enzymes, antibodies and other small molecules. Despite their miniscule size, delivering these therapies to patients’ bodies can prove difficult.

According to an info sheet from the Wisconsin Alumni Research Foundation, ingesting these treatments doesn’t work, as the polypeptides are broken down through digestion or otherwise blocked from reaching the bloodstream. Therefore, these treatments are usually introduced directly to the bloodstream through an IV. 

Still, that common method poses its own problem. Certain genetically engineered bacteria have been used to deliver the treatments to specific parts of the body, but some patients with weaker immune systems can be negatively affected. 

Using experimental mouse models, researchers have demonstrated they can engineer bacteria to deliver therapeutics while avoiding substantial pollution of the bloodstream with the bacteria, the info sheet shows. 

While the researchers say their method is comparatively non-invasive and effective, they also claim it represents an “inexpensive approach … that would otherwise be cost-prohibitive.” 

This method could also be used to deliver insulin to diabetic patients, or to treat a condition called arteriosclerosis, which refers to the buildup of fats, cholesterols and other substances along artery walls. 

The scientists engineered a form of bacteria to deliver a protein called interleukin-22, or IL-22. Because IL-22 has previously been shown to alleviate metabolic disorders such as diabetes, researchers tested whether they could replicate those effects with IL-22 secreted by their specialized bacteria. They used mice with diet-induced obesity. 

The mice that were given this oral treatment had many symptoms of their metabolic syndrome reversed, according to the info sheet. All subjects experienced “systemic physiological effects” including increased growth, increased growth hormones, and reductions in liver weight and overall body mass index. 

Building on those results, researchers predict that systemic delivery of the IL-22 protein would reverse the symptoms of diabetic subjects, including high blood sugar levels and resistance to insulin — the hormone that signals the body to absorb glucose from the bloodstream. They expect it will decrease associated chronic inflammation and improve liver function for subjects with diabetes. 

WARF is seeking commercial partners interested in licensing the bacteria to lower the risk of delivering therapeutic treatments. 

See the info sheet: http://www.warf.org/technologies/summary/P160109US02.cmsx