NEW YORK (GenomeWeb) — Islet Sciences, a Raleigh, NC-based biopharmaceutical company, said yesterday that its collaborators at Yale University School of Medicine have published key data demonstrating the efficacy of a novel droplet-based digital PCR (ddPCR) diabetes diagnostic.
Islet holds an exclusive license to the epigenetic test, which detects methylation status of cell-free DNA in order to track pancreatic beta cell death. Company representatives said this week that Islet intends to commercialize this assay by 2015.
The study, published online in Endocrinology last week, suggests that the ddPCR approach is the first of its kind, and enables accurate quantification of the extremely low levels of insulin gene DNA released into the blood by dying beta cells.
In an interview with PCR Insider, Islet Chief Operating Officer William Wilkison said the assay relies on the fact that the insulin gene is hypomethylated in pancreatic beta cells, but hypermethylated in cells elsewhere in the body. Hypomethylated cell-free insulin gene DNA is therefore thought to derive from dying beta cells, and levels in serum can be used to gauge the rate at which beta cells are being lost.
In the Endocrinology study, the ddPCR assay was first optimized on samples containing mixtures of hypo- and hypermethylated insulin gene DNA. It was then used to quantify clinical serum samples of 39 non-diabetic control subjects, 43 subjects within the first year after diagnosis of type 1 diabetes, and 26 at-risk subjects.
"This highly sensitive technique not only allowed researchers to distinguish patients with recent onset type 1 diabetes from non-diabetic control patients, but also for the first time provided evidence of ongoing beta-cell loss in non-diabetic patients who are at risk of developing disease based on family history and other factors," Islet Sciences said in a statement.
The study suggested that ddPCR might be particularly useful in uncovering beta-cell loss in "normoglycemic" at-risk individuals. Hyperglycemia, the signature symptom of diabetes, usually begins after approximately 80 percent of beta cells have already been destroyed, the study said. An accurate method to detect beta-cell loss at an early stage may therefore enable medical intervention at a time when available therapies or lifestyle changes could have the greatest benefit.
James Green, CEO of Islet, said the market for this test is potentially quite large. There are over 25 million diagnosed diabetics in the US, with an estimated 25 million more undiagnosed, he said. "Then there is a very large number that are at risk for diabetes, both type 1 and type 2," he said.
"The whole diabetic population would benefit from this assay, but, because it is a diagnostic, I think these undiagnosed and at-risk patients stand to benefit the most," he said.
Green said the company is now "going to work as quickly as possible to bring this to market."
"There are a lot of pieces to be put into place ... there's a bit of a continuum of options that we have, so I would suspect that 2015 would be a safe bet for us to bring something to market for type 1 diabetes," he said, with type 2 diabetes-oriented testing available some time after that.
Wilkinson explained that Islet learned of this assay through consultation with its network of collaborators. It then reached out to the lab at Yale, and negotiated the license in 2012. The assay is predictive not only in type 1 diabetics, but also in several animal models of diabetes, he said.
Currently, there is no commercially available molecular method to track beta cell loss, Wilkinson suggested. "We've recently been aware of PET scan [methods] ... but that's a very cumbersome and time-consuming way of tracking beta cell number [and it] requires a lot of special equipment. Our assay does a much better job, with a simple blood sample."
The test will ultimately be lab-based, and it might be adapted to a hospital lab setting "very easily," Wilkinson said. "In fact, the basic design of the assay may not change very much. It's very simple, it's extremely quantitative and accurate, and we anticipate it being something that physicians will use as part of their diagnosis and treatment design," he said.
Islet's immediate next steps, however, are still being determined. "We want to take this forward as an approved diagnostic, ultimately," Wilkinson said. "Having a CLIA lab is one way of doing that which we are thinking about."
The published assay used the Bio-Rad QX100 Droplet Digital PCR platform. However, Wilkinson said any droplet-based digital PCR platform might be suitable for this work, and Islet has not looked into others at this time.
"The ability of our assay to be implemented on any or all of the platforms gives us the option of who we want to work with," he said. "This may be something that we are going to consider in the future, looking at the different manufacturers and seeing which machines might gain us a benefit in cost, or speed, or accuracy."
Meanwhile, the lab that originally developed the assay will continue to use it in clinical work, for example, to study whether beta cell death can be reversed, Wilkinson said.