David Walt’s lab at Tufts University appears to be immune to the trend of tighter National Institutes of Health budgets after it recently pocketed more than $2 million to support a variety of projects related to the development of array-based salivary diagnostics.
The goal is to develop a point-of-care diagnostic device that uses saliva to detect “asthma exacerbation,” Walt said. The project involves multiple institutions and commercial partners, including Boston University, the University of Pennsylvania, the Tufts computer science department, and Ahura Corp.
There is ample NIH support. In July, the agency awarded Walt’s lab $1.7 million to support ongoing work on saliva-based asthma diagnostics, and last month, his lab netted an additional $375,000 from the agency for a related project.
Walt told BioArray News via e-mail that the first phase of the salivary diagnostics project, which began in 2003, received approximately $4 million from the NIH over four years. The lab is just now beginning the second year of Phase 2 of the project, which is funded for five years for an expected total of $8.75 million.
While there are a number of collaborators on the project, it is Walt’s connection to Illumina, which he co-founded in 1998 and where he still serves as chairman of the scientific advisory board, that could provide the final avenue to market the tests..
Among several technologies that Walt’s lab is developing is an assay to determine the severity of an asthma attack. This assay relies in part on the same microbead array technology that underlies Illumina’s products, which Tufts licensed exclusively to the company in 1998.
Walt said that that the company is working with his lab on some of the assays under development, but he stressed that any point-of-care system that results from that work will likely use a combination of bead array technology and microfluidics.
Specifically, the saliva-based asthma tests will use the array format combined with a microfluidic system for sample preparation and reagent addition. The arrays will also contain both protein and nucleic acid markers.
“Right now we have two separate arrays that are being integrated into a single microfluidic platform but we are working on putting both marker types on the same array,” Walt wrote in an e-mail to BioArray News. “Stay tuned.”
The goal is to be able to provide clinicians with a rapid diagnostic test for asthma, which is a common cause of emergency room visits in the US.“We would like to be able to determine the severity of an asthma exacerbation from inflammatory markers in saliva as well as the cause of the exacerbation [such as] bacterial infection, [or] exposure to allergens such as pet dander,” he wrote.
“By looking at different components of saliva, we hope to be able to provide the physician with the information needed to properly treat a patient based on these markers rather than using only clinical symptoms,” he added.
Hunting for Asthma Markers
A good portion of Walt’s work is spent on developing markers for the test. The latest $375,000 NIH grant will fund the development of arrays for the Human Salivary Proteome Project hosted by the University of California, Los Angeles. The project seeks to generate a complete catalogue of all salivary secretory proteins, information that could later be used to create a better asthma test.
“Saliva contains both cells and fluid,” Walt pointed out. “It is highly viscous and contains certain proteins at high concentration that can interfere with an analysis. Right now we are honing in on identifying markers in saliva that correlate with asthma.” He added that his lab hopes to have a research version of the test in the field next summer.
The NIH grant runs through 2012, a date that “sounds right for when we would be ready to commercialize something, assuming we get good results in the trials,” Walt said.
“Illumina would be the obvious partner for supplying the arrays, but it is too early in the process for them to be interested in a serious way at this point.”
For its part, Illumina also sees the project as a long-term affair. In an e-mail to BioArray News last month, CEO Jay Flatley described the test as a “research project” that is “a long way from any commercial product.”
This week, Walt wrote, “Illumina would be the obvious partner for supplying the arrays, but it is too early in the process for them to be interested in a serious way at this point.”
Furthermore, he wrote that while Illumina could play a role, the multi-platform format of the system under development indicates that other firms will also be involved in the commercialization process. “The system we are developing contains a multitude of technologies including microfluidics, arrays, and the optoelectronic reader that will require the cooperation of several commercial entities,” he wrote.
Meantime, Walt’s lab is moving ahead with another potential product that grew out of the preliminary work for the asthma test: using saliva to help diagnose kidney disease.
This is a logical step for his lab. According to Walt, when his lab first started the asthma project it also studied renal patients as a proof of principle. “Dialysis patients were an ideal patient cohort because we knew that certain substances were removed from blood during dialysis and wondered if we could measure the progress of dialysis using saliva samples,” he wrote.
After screening several dozen analytes for relevance in pre- and post-dialysis patients, Walt’s lab determined that it could monitor the efficacy of dialysis using only two analytes: uric acid and nitrate. The team then decided to convert the assay to a testing strip format because “a duplexed assay does not require a sophisticated array.”
Ideally, patients would use these strips at home to monitor their renal function. Walt’s hope is that the test could eventually be used by kidney patients who do not need dialysis yet but who do need to test their blood frequently to make sure their disease has not progressed.
“These patients could perform home monitoring of their saliva rather than needing to have their blood tested on a weekly basis,” he wrote. “If higher-than-expected levels of the two analytes are found in their saliva, they could report for a blood test. We have tested these strips in the clinic and are now planning to test these strips in a home setting in a select group of patients,” he added.
Walt did not provide a timeline for commercializing the renal function test strips.