Columbia scientist touts potential of a new diabetes therapy

An investigator at Columbia University Medical Center with close ties to Tarrytown, NY-based Armgo Pharma has published new animal data to back up the promise of their clinical-stage diabetes drug Rycal.

Senior author Andrew Marks, a professor at Columbia and an adviser to Armgo, starts out with the observation that ryanodine receptor type 2 (RyR2) calcium channels in insulin-producing cells play a previously unknown role in balancing glucose. Those channels control the intracellular release of glucose. But when they are "leaky," the pancreas releases less insulin, triggering high blood sugar levels.

Working with mouse models for the disease, Marks says they were able to use the experimental Rycal to plug the leaks and rebalance glucose--offering a new approach to diabetes and possibly preventing the ailment from developing in at-risk patients.

"We've known that calcium in the pancreatic beta cells plays a significant role in regulating insulin secretion, but calcium levels were thought to be controlled largely by the entry of calcium into the cell," said Marks, professor and chair of physiology and cellular biophysics. "It turns out that there's another mechanism in pancreatic beta cells that also controls calcium. This mechanism involves RyR2 channels, and leaks in these channels can lead to impaired glucose tolerance. These findings open up a whole new area of research into the molecular underpinnings of prediabetes and diabetes and point to potential therapeutic targets."

Their work was triggered by some unexpected observations on a study related to exercise-induced arrhythmia, which can be triggered by mutations in the RyR2 gene.

Armgo has kept a low profile in the biotech business, but the biotech involves some prominent investigators and execs. Sapan Shah, the former CEO at Shionogi, was tapped to helm Armgo in 2011. Since then the biotech has worked on RyR as it related to cognitive dysfunction as well as Duchenne muscular dystrophy (DMD) and spinal bulbar muscular atrophy. Back in 2006 the company formed a partnership with Servier on DMD and late last year outlined an early-stage clinical program for the disease.

This new research on diabetes was funded by a variety of groups, including the NIH and the American Heart Association.

"The advantage of a Rycal is that many drugs now used to treat Type 2 diabetes increase the risk for low blood sugar and for heart disease," said Marks. "Based on the mechanism of action of Rycals, we would not expect this drug to cause either of these. Also, Rycals are currently being tested in patients with heart disease and muscle disorders and have a good safety record so far." 

The findings were published in the online edition of the Journal of Clinical Investigation.

- here's the release
- get the research article

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