By Ben Butkus
Norwegian molecular diagnostics developer DiaGenic this week announced a research agreement with GE Healthcare to develop a blood-based test using DiaGenic's peripheral gene expression profiling technology in patients with mild cognitive impairment, a disorder with risk for progression to Alzheimer's disease.
The study will be the "first ever" to combine blood-based gene expression testing with PET imaging, and could produce a molecular diagnostic test that would help identify which patients might benefit from a PET imaging procedure, DiaGenic CEO Erik Christensen told PCR Insider this week.
In the meantime, DiaGenic will continue to pursue US Food and Drug Administration approval for a similar blood-based gene-expression test, called ADTect, for the early detection of Alzheimer's disease — an effort that would likely require another partnership with a large pharmaceutical or diagnostic company, Christensen said.
As part of its research agreement with GE Healthcare, DiaGenic will attempt to correlate its peripheral gene expression profiling technology — which uses Life Technologies' ViiA7 multiplex PCR instrument and microfluidic TaqMan real-time PCR cards — with information gleaned from PET imaging of amyloid plaques in the brain.
The PET imaging agent, [18F] flutemetamol, is currently in phase 3 development and is not yet approved by any regulatory authority. DiaGenic and GE Healthcare will "combine expertise in data integration, informatics, genomics, and imaging … to find a signature that may identify subjects at risk of Alzheimer’s at a very early disease stage," the companies said.
"The output of the collaboration will be a blood-based test that supports or qualifies the use of a PET tracer," Christensen said. "So it's a combination device, if you will. PET [imaging] is a high-cost investigation, and Alzheimer's is a huge disease, so you need to identify the right people that should go for a PET [scan]. And at the same time, [healthy individuals] shouldn't have to be exposed to radioactive tracers."
For the project, the team will "aim to recruit 180 individuals with amnestic [mild cognitive impairment], together with 30 patients with clinically diagnosed mild to moderate AD," Oskar Hansson, a researcher at Lund University and Skåne University Hospital and PI on the study, said in a statement. "Clinical assessment together with high-quality blood and imaging tests for the very early stages of AD will bring tremendous value to the clinicians and drug developers."
Innovation Norway has granted NOK 2 million ($348,000) to the project through its Industrial Research and Development Contracts Program. The project will also be eligible for a tax deduction through SkatteFunn, a Norwegian tax credit scheme designed to support innovation from Norwegian companies, DiaGenic said.
DiaGenic, which is publicly traded on the Oslo Stock Exchange, has for several years been developing its blood-based gene expression tests for MCI and Alzheimer's; as well as a test for breast cancer, called BCTect.
Both ADTect and BCTect have CE IVD marking and are commercially available in Europe. However, in 2010 following a private placement worth NOK 70 million ($12.1 million at the time), DiaGenic Chairman Henrik Lund said that the company would for the time focus its attention on its ADTect and MCI assays (PCR Insider, 10/7/2010).
ADTect originally examined a panel of what DiaGenic found to be 96 of the most important genes from a group of several hundred covering a wide array of biological processes and changes in early Alzheimer's disease.
The test was also originally based on array hybridization and ran on the now-defunct Applied Biosystems 1700 chemiluminescent microarray analyzer. However, DiaGenic eventually adapted the test to real-time PCR technology, at first on the Life Technologies ABI 7900 HT platform.
More recently, as part of a collaborative study with Pfizer begun in December 2010, DiaGenic whittled the 96-biomarker panel down to a set of 20 genes identified to have the ability to discriminate stable mild cognitive impairment from MCI that converts to Alzheimer's. The company presented initial data from that effort at the Clinical Trials Conference on Alzheimer's Disease in November in San Diego.
For that study, DiaGenic also moved the test to Life Technologies' relatively new ViiA7 multiplex PCR instrument (PCR Insider, 4/22/2010) and the microfluidic TaqMan real-time PCR cards, Christensen said this week.
Life Tech's TaqMan Array microfluidic cards can include up to 384 targets on a single 384-well consumable, and in fact, when DiaGenic's assay targeted 96 genes it was running four patient samples per card, Christensen said.
Since DiaGenic expects that its final test will interrogate "20-some genes," Christensen said the company will likely adapt it to customized 48-target TaqMan microfluidic cards.
It is unclear whether the MCI test that DiaGenic is investigating along with GE Healthcare will target the same 20-gene panel as the current version of ADTect, but Christensen noted that the study will use the ViiA 7 platform and TaqMan cards.
DiaGenic continues to pursue US regulatory approval of its ADTect test, but as a small company with limited resources it will likely need to find a partner to do so, Christensen said.
"DiaGenic has been running clinical trials [for ADTect] for a number of years now, including in the US, so we are building that documentation base," he said. We are building the documentation and trying to understand the FDA process and plan accordingly, but we are a small company and need a large partner to enter the US market."
Christensen added that DiaGenic has been talking about the test with "a number" of pharmaceutical companies in the wake of its collaboration with Pfizer, which owns some rights to the 20-gene panel since it partially funded the research. "They have some rights to use our product in their internal R&D," Christensen said. He declined to identify which potential pharmaceutical partners DiaGenic is in discussions with.
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