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Nottingham Group Wins $1.1M for Alzheimer's Protein Biomarker Research


By Adam Bonislawski

A University of Nottingham research group has received a two-year, £670,000 ($1.1 million) grant from the UK's Medical Research Council to develop a chip-based surface plasmon resonance imaging platform to detect Alzheimer's disease.

At the end of the grant the scientists hope to have a prototype of the platform that can be turned into a commercial instrument for use in Alzheimer's screening and potentially by pharma companies for drug development, said Paul O'Shea, a professor of biophysics and biomaterials at the university and leader of the project.

"We envisage an instrument that can sit in a point-of-care [or] medical center for screening and a more advanced instrument drug companies [can use] to assess the efficacy of drug treatments," he told ProteoMonitor in an email.

Alzheimer's biomarkers are a major area of protein biomarker research and are expected to represent a cumulative $9 billion market over the next ten years according to a recent report commissioned by proteomics firm Proteome Sciences (PM 06/13/2011). In addition to their promise for diagnosis and predicting progression of the disease, early detection and progression biomarkers are also expected to play an increasing role in pharmaceutical research into drugs for the disease.

Much Alzheimer's protein biomarker work has revolved around measuring amyloid beta-42, tau, and phospho-tau in cerebrospinal fluid. According to O'Shea, the Nottingham panel includes Abeta1-42 and tau, but also includes roughly seven additional protein markers that the researchers have patented for the detection of Alzheimer's. A number of these proteins were identified as potential biomarkers through recent genome-wide association studies led by Nottingham researcher Kevin Morgan, said Bajaj Nin, a neurologist at Nottingham University Hospitals who is coordinating clinical studies using the panel.

Thus far the researchers have tested the biomarkers in CSF samples from several hundred subjects, including Alzheimer's patients, people suffering from mild cognitive impairment, and healthy controls, Nin told ProteoMonitor, noting that it has proven "highly accurate for differentiating Alzheimer's dementia from mild cognitive impairment and normal controls." Next spring, he said, they plan to start a new trial to see whether the results obtained using banked samples will hold up in a clinical setting.

"We'll probably be looking at around 100 patients to see how this works in the clinic and whether it will prove just as accurate for the diagnosis of patients of first attendants." he said. "We're going to be comparing the proteomic diagnoses to the best clinical diagnoses available" including those made using high resolution MRI and PET scanning.

Nin said that the team also plans in this trial to use plasma as the sample material instead of CSF, which was used for much of the work on the banked samples. Blood is a more desirable medium because it's easier to obtain than CSF, which is typically taken via a lumbar puncture. As Holly Soares, director of clinical neuroscience biomarkers at Bristol-Myers Squibb and told ProteoMonitor in an interview last year, blood is particularly attractive from pharma's perspective because it could provide drugmakers — a number of whom are currently engaged in Phase III trials for Alzheimer's therapeutics — with a way of selecting subjects that could be considerably less expensive than current methods like CSF analysis and PET scans.

Alzheimer's-linked proteins are typically found in lower concentrations in blood than in CSF, however, making it more challenging to detect biomarkers in this medium. Blood also contains a number of high-abundance proteins like albumin that, Nin noted, "sort of swamp the signal of everything else."

"There are a number of obstacles to overcome," he said, but results from initial tests using banked blood samples "look good, so we're hopeful that is will work [on blood] in real time."

The primary aim of the upcoming trial is to "confirm that [the panel] is a good, robust diagnostic test for Alzheimer's," Nin said. "We then want to confirm that it will differentiate both normal controls and MCI from Alzheimer's. Thirdly, we want to see if we can map progression from Alzheimer's, comparing mild, moderate, and severe [cases]."

Down the road, the researchers also hope to look at the predictive value of the test, he said, "to see if we can tell which MCI patients will go on to get Alzheimer's and which will not."

They also hope to use it to predict patient drug response, "profiling the blood from people on cholinesterase inhibitor-type drugs to compare people who do well on those drugs versus people who don't," Nin added. He said that "if the blood work next spring looks promising" pursuing collaborations with drug companies for work with the panel "would be one of the next phases."

According to O'Shea, the researchers are currently in talks with several pharma and biotech firms regarding the platform, although he declined to name any specifically. "Over the next year [we] will develop these discussions to identify the best partner," he said.

The detection platform, which uses plasmon resonance imaging combined with a proprietary complementary metal oxide semiconductor camera system, is applicable to diseases beyond Alzheimer's, Nin noted, and while the MRC grant is specific to their Alzheimer's work, the researchers are currently using the system to explore biomarkers for other neurological disorders as well as non-neurological diseases, he said.

"The platform is generic. You just have to change the panel of proteins that you're looking to detect," he said. "So this will be a powerful platform that can be adapted to a whole range of other disorders."

Have topics you'd like to see covered in ProteoMonitor? Contact the editor at abonislawski [at] genomeweb [.] com.