This story originally ran on April 26.
Arizona State University's Biodesign Institute has won a four-year, $30.7 million contract from the US Department of Defense's Defense Threat Reduction Agency to build a prototype of a proteomics-based health monitoring chip.
The project aims to package immunosignaturing technology developed in the lab of Stephen Johnston, director of the institute's Center for Innovations in Medicine, into devices that can be used in the field for monitoring subjects' health and early detection of pathogen infection.
Developed over the last seven years by Johnston and several colleagues at the Biodesign Institute, immunosignaturing uses random-sequence peptide microarrays to capture antibodies in patient blood samples (PM 2/4/2011). Based on the levels of antibody binding, researchers build antibody expression profiles that can then be correlated with various disease states.
The DTRA contract calls for Johnston and his team to incorporate this technology into a "fieldable" device that can be used to monitor soldiers for infectious diseases.
While pathogen detection work has typically relied on biochemical- or PCR-based testing, proteomics has of late made inroads into the space, with companies including Bruker, Quanterix, and BioMérieux applying proteomic techniques to pathogen detection (PM 8/19/2011).
Immunosignaturing differs from these methods, however, in that, rather than detecting pathogen proteins, it seeks to use the host's immune response for detecting infection. This approach, Johnston said, could offer better sensitivity and allow for improved stratification of patients by severity of infection.
"We've been arguing for many years that [researchers] should be putting more emphasis on detecting host response than detecting the pathogen itself," he told ProteoMonitor, offering the case of severe acute respiratory syndrome, or SARS, infections as an example.
"When the SARS infections took place, 85 percent of the people who got it resolved it [without need for medical attention.] Only 15 percent of the people needed any attention, and only five percent needed critical attention," he said. "But [using conventional techniques,] we had no way of telling who was who. So, what we are arguing is that if we could see what the host was doing we could respond more appropriately."
Doctors could also potentially respond earlier, Johnston said, given the rapidity of the body's immune response. Clinicians could characterize individuals' immunosignatures when healthy, providing a baseline against which disturbances could be detected.
The DTRA award, which consists of an initial one-year, $9 million contract along with an optional three-year, $21.7 million contract, will support efforts to establish such baseline immunosignatures, Johnston said.
With the funds, the Biodesign researchers plan to monitor an initial group of 200 subjects for several months, measuring their immunosignatures on a weekly basis. They will then expand that cohort to 1,000 ethnically- and age-mixed subjects.
The contract will also fund efforts to build a prototype of the device itself. Currently the Biodesign Center uses slides featuring 10,000-peptide microarrays, but, Johnston said, his team is now able to build slides that feature 24 chips per slide and 330,000 peptides per chip. "The more peptides we can put down and the higher the quality of them, the better the signal information we get," he noted.
Production of these high-content, high-quality chips has, in fact, been among the largest hurdles the researchers have faced in developing the method, Johnston said.
"There's a lot of chemistry we had to deal with," he said. "If you're making something on these little features, how do you look at that chemically to see whether it's right or not? Those technologies really weren't there, so we have to develop them ourselves in order to make progress on the [array] synthesis."
Beyond the DTRA work, Johnston and his colleagues have been exploring the technology for use in a variety of indications, including Alzheimer's disease and breast, brain, and pancreatic cancer.
He has also founded a company, Healthtell, to commercialize the method. Currently, he said, the firm – which has six employees – is focused almost exclusively on chip production, with the biology side of the work being done through subcontracts back to the Biodesign Institute.
The company is currently working on diagnostics for two diseases — coccidioidomycosis, or Valley fever, in humans, and lymphoma in dogs – that Johnston said would likely be available for use within a year. The researchers chose to focus on a veterinary indication due to the simpler regulatory process for such tests, he said. "It's a short pathway to actually get [such tests] used."
Ultimately, Johnston said, he hopes to develop the technology as a direct-to-consumer product that will allow people to monitor their health status by regularly mailing in blood or saliva samples for analysis. To that end, his team recently conducted a study examining the stability of immunosignatures, publishing the results in a paper in Clinical and Vaccine Immunology.
"Our goal is that everybody will monitor their health on a regular basis," he said. "So if you're going to do that you want to have some really robust way for people to send you their samples. So we wanted to look into that carefully to make sure the idea that someone would send in a drop of blood or spit on a regular basis was practical."
The study found that dried blood spots sent through the mail yielded usable immunosignatures and that dried blood spots stored at high temperatures remained usable for immunosignaturing.
The researchers also examined use of saliva as a sample, finding that it was also sufficiently stable but that it contained a lower concentration of antibodies. Given this, Johnston said, "we would really prefer to have blood samples."
He noted that "some people are reluctant" to perform finger pricks on themselves, but suggested that new micro-needle sampling technologies, "where taking the blood is totally painless," could lessen that reluctance.
Regulatory questions will likely prove a more significant issue for Johnston and Healthtell's DTC proteomics plans – at least if the sagas of DTC genetic firms like 23andMe, Decode Genetics, and Navigenics are any guide.
After launching their first tests three years ago, DTC genomics firms maintained for several years an uneasy relationship with the US Food and Drug Administration, marketing their services largely as laboratory-developed tests over which the agency has traditionally exercised "enforcement discretion." In May 2010, however, in response to Pathway Genomics' plans to sell genomic sample-collection kits at retail stores Walgreens and CVS/Caremark, FDA sent letters to four major genomic testing companies instructing them to submit their products for review and clearance by the agency (PGx Reporter 06/16/2010).
Just over a month later, the Government Accountability Office issued the results of its own year-long investigation of DTC genomics testing, concluding that the companies' test results were "misleading and of little or no practical use to consumers" (PGx Reporter 07/28/2010). Since then, several firms, including Pathway and Navigenics, have changed their business models to require physician involvement in the testing process.
Though their DTC aims are somewhat unique for proteomics, Johnston and Healthtell aren't alone in their immunosignature approach. Earlier this month, Opko Health signed a deal with Laboratory Corporation of America for use of its immunosignature-based Alzheimer's diagnostic technology (PM 4/6/2012).
Similar to Johnston's technique, Opko measures levels of Alzheimer's-associated autoantibodies in patient plasma to detect the disease. Detailed in a paper published last year in Cell, the system uses synthetic molecules called peptoids to screen for autoantibodies in blood (PM 1/7/2011).
In addition to its Alzheimer's work, Opko is using the platform to research autoantibody-based biomarkers for various cancers, autoimmune diseases, neurodegenerative diseases, and infectious diseases.