Researchers at the Texas Alzheimer's Research Consortium have used protein biomarker data developed on Rules-Based Medicine's DiscoveryMAP immunoassay platform to build a serum-based test designed to detect Alzheimer's disease.
The test is the latest of several Alzheimer biomarker panels developed on RBM's DiscoveryMAP platform, and the company plans to develop a smaller, specialized Alzheimer's immunoassay for research and clinical trial use by next year, with a laboratory-developed test potentially following shortly thereafter, Sam LaBrie, RBM's vice president of corporate development, told ProteoMonitor this week.
"Over the last several years we've been part of, I guess, a consortium of consortia," he said. "There are several large groups that are working on collecting Alzheimer's disease and mild cognitive impairment patients, and we've been processing a lot of these blood samples on our platform in hopes of finding biomarker patterns important for Alzheimer's diagnosis."
In addition to TARC, RBM has processed samples from the National Institutes of Health-funded Alzheimer's Disease Neuroimaging Initiative and the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing.
"What we've tried to do is get access to these great sample sets and process them on our platform in hopes of being in the middle of what should be a pretty interesting commercial opportunity as biomarker patterns are discovered and validated," LaBrie said. He noted that nearly all the major pharmaceutical companies have Alzheimer's research programs.
The ultimate goal, he said, is developing a protein biomarker-based diagnostic capable of predicting progression from MCI to Alzheimer's.
"Everyone's hope is that we can find something for progression," he said. "The drug-development groups we've spoken with, that's the application they want for the new therapeutics they're developing – to be able to treat someone earlier in the life cycle of the disease. It's disease-modifying therapy rather than some of the current therapies that address the later symptoms."
The TARC test, which is described in a paper in the current issue of the Archives of Neurology, focuses only on detecting Alzheimer's rather than tracking its progression from MCI. But the group has an NIH grant under review to fund a cross-validation study of the test and research into biomarkers predicting progression from MCI, Sid O'Bryant, assistant professor at the Texas Tech University Health Sciences Center and TARC researcher, told ProteoMonitor.
The consortium is also interested in looking at endophenotypes of the disease. The Archives of Neurology paper, which examined 197 Alzheimer's patients and 203 controls, identified 10 inflammatory-related biomarkers, suggesting the existence of an inflammatory endophenotype within some Alzheimer's cases that could prove useful for developing targeted therapies, O'Bryant noted.
"Cardiology has been doing this for years," he said. "For example, with cholesterol, someone who has high [high-density lipoprotein or low-density lipoprotein] – those are two different things that you may treat differently.
"So where we think this will go in the long run is we'll look at Alzheimer's disease patients and say, 'This is your particular profile, and we can target your treatment based on that profile itself,'" he said.
The researchers have another paper under review designed to further investigate the inflammatory endophenotype, and separately plan to look for endophenotypes related to vascular functioning and oxidative stress, O'Bryant said.
The Archives of Neurology study was also able to determine whether or not subjects had Alzheimer's with 80 percent sensitivity and 91 percent specificity. Adding age, sex, education, and APOE epsilon 4 status to their algorithm, the researchers achieved 94 percent sensitivity and 84 percent specificity – results equal to those of protein biomarker tests developed using cerebrospinal fluid, O'Bryant said.
A blood-based diagnostic such as TARC's could be more desirable than a CSF-based assay because of the difficulty of collecting CSF samples.
TARC comprises researchers at five institutions throughout Texas: Baylor College of Medicine, Texas Tech University Health Sciences Center, The University of Texas Southwestern Medical Center, University of North Texas Health Science Center, and The University of Texas Health Science Center at San Antonio.
Established by the Texas legislature in 1999 and launched in 2005, the consortium to date has enrolled 800 subjects, and by the end of this year it will have enrolled roughly 1,200 subjects – 600 Alzheimer's patients and 600 controls – each of whom it will see annually, O'Bryant said.
"It's a prospective cohort, so we add aims as we finish a project," he said. "We have an incredible amount of data still to analyze and samples still to be assayed because we have a baseline on a lot of people, but we still have so much follow-up [to do]. This is a project that is designed to continue for some time to come."
The group plans to continue using RBM for future assays, he said, although it may add additional platforms as it works to refine its algorithms.
RBM, meanwhile, must combine the many Alzheimer's sample sets it has run to develop a cutdown panel specific to the disease. One challenge is the fact that the different research groups have investigated biomarkers in a variety of different sample types, including serum for TARC and plasma and CSF for ADNI.
"There's some reconciliation that has to happen," LaBrie said. "It's going to take some time, but we expect that in the near future we'll be able to designate a cutdown panel. It's just pretty expensive to run DiscoveryMAP on thousands of samples. We're pretty sure we know which markers are important."
The final panel will probably involve "a couple dozen" markers, compared to DiscoveryMAP's 189, he added.