Thursday, October 30, 2008

Smart Insulin

An experimental drug for diabetes dispenses insulin in response to glucose levels.

By Jennifer Chu

Smart shots: A new drug that senses glucose levels and delivers insulin on demand may reduce the number of daily injections for patients with diabetes. SmartInsulin works via competitive binding, in which insulin (orange lines), attached to a sugar group (orange hexagons), binds with a sugar-binding molecule (blue circle) in solution. When glucose (blue hexagons) in the body is high, it competes with insulin to bind to the sugar-binding molecules, displacing insulin and releasing it into the bloodstream as needed. Credit: SmartCells

Maintaining tight control over blood-sugar levels is a daily challenge for people with diabetes: it requires constant monitoring and multiple insulin injections each day. Now the biotech company SmartCells, based in Beverly, MA, is developing a drug that may do most of the heavy lifting in controlling diabetes. The injectable drug, called SmartInsulin, senses high glucose levels and automatically dispenses insulin on demand. As glucose levels drop off, the drug stabilizes, trapping insulin until the next glucose spike. Such a drug may cut down the number of insulin injections required to once a day.

Todd Zion, founder and CEO of SmartCells, says that such a self-regulating drug may also reduce the risk of hypoglycemia, a potential hazard associated with current diabetic therapies. "You will find with any person taking insulin [that] the most dangerous risk is accidental overdose, or not being able to predict how blood sugar will swing after a meal," says Zion. "From a treatment standpoint, this [drug] would eliminate the risk of dangerously low blood sugar."

Normally, beta cells in the pancreas release the hormone insulin into the bloodstream in response to high glucose levels. The hormone curbs glucose levels by helping the body's cells absorb it as fuel. In diabetes, insulin production is impaired, leading to abnormally high levels of circulating glucose. That results in serious consequences, including blurred vision, changes in metabolism, and sudden weight loss.

Diabetes patients currently take insulin via pens and traditional syringes, which deliver a single dose of the drug, or via insulin pumps, which provide continuous low doses throughout the day and may deliver insulin during periods when it's not needed. SmartCells' alternative is to chemically modify insulin in such a way that the active hormone is released only in the presence of a certain concentration of glucose. Below that level, insulin remains bound and insoluble until the next blood-sugar spike.

Zion developed the technology while working as a doctoral candidate in MIT's Nanostructured Materials Lab, which is led by professor Jackie Ying. In his experiments, Zion modified insulin by chemically attaching it to a biodegradable polymer containing sticky sugar groups. He then mixed it in solution with a sugar-binding molecule, which, in the absence of any other sugars, immediately binds to the sugar groups attached to the insulin. As more binding molecules grab on to more modified insulin, a network forms that holds the insulin in place. When glucose is added to the system, it bumps the insulin-bound sticky sugar group out of the way, grabbing on to the sugar-binding molecule. The more glucose there is, the more insulin is shed from the network, dissolving away. "You can see these particles shrinking and the insulin coming off them, depending on how quickly they're being attacked by sugar from the body," says Zion.