NEW YORK (GenomeWeb) – Ceres Nanosciences has begun offering its urine-based Lyme disease diagnostic nationwide.
The company this month also received $500,000 from the Virginia Biosciences Health Research Corporation to develop a version of the test that will also incorporate detection of other tick-borne diseases that present similarly to Lyme.
The test is based on Ceres' Nanotrap technology, which uses hydrogel nanoparticles functionalized with internal affinity baits to enrich target analytes for downstream analysis. The system uses chemical dyes to bind analytes of interest, concentrating them inside the nanoparticles and protecting them from enzymatic degradation, thereby improving the sensitivity of the ultimate clinical detection method — for instance, ELISA or mass spec.
In the case of the company’s Lyme test, the assay detects a specific portion of the outer surface protein A (OspA) of Borrelia, the tick-borne organism that causes Lyme disease. Current Lyme tests typically measure a patient’s immune response, looking for antibodies to the disease in a patient’s blood. However, particularly in early-stage disease, when a patient might not yet have raised a large immune response, these tests can often give false negative or inconclusive results.
More recently, clinicians have begun using PCR-based tests to detect Borrelia nucleic acids directly. However, because Borrelia is present in patient blood only at very small concentrations, these tests often lack the necessary sensitivity.
Ceres this month published a study of its test in the Journal of Translational Medicine, data from which it is using to support its use for early diagnosis of Lyme disease, GMU researcher and company co-founder Lance Liotta told GenomeWeb.
As Liotta’s GMU colleague and Ceres co-founder Emmanuel Petricon told GenomeWeb, OspA is a potentially useful target because the organism sheds multiple copies into the bloodstream, and so the protein may be present at significantly higher concentrations than the organism itself.
This, combined with the Nanotrap technology, he said, makes for a test with potentially much greater sensitivity than existing assays.
In the JTM paper, the researchers looked at 24 patients with a clinical diagnosis of Lyme disease, 12 of which had positive serology, five of which had negative serology, three for which the serology was indeterminate, and four for which serology was not tested. All 24 of these patients tested positive for Lyme disease using the Ceres test.
They also looked at 120 patients without Lyme disease, three of whom were symptomatic and 117 of whom were asymptomatic. All 120 tested negative using the Lyme test.
Based on these results, the company has begun offering the test nationwide. However, while it appears useful for early detection, establishing its usefulness in later-stage cases is tricky, Liotta noted, given the difficulty of identifying cohorts of truly Lyme positive patients.
“Say the patient has had Lyme disease for years,” he said. “Obviously the bullseye rash is gone. It is very difficult to culture the bacteria from blood. So what do you do with that patient? Do they have Lyme or not? It’s a very difficult question.”
Liotta, Petricoin, and their colleague nonetheless looked at 100 such patients in the JTR study, finding that roughly 40 percent were positive based on the Ceres test. Positioning the test for such a use will be difficult, though, given the aforementioned challenge of establishing true positive patients. “So we are not offering this for that kind of indication.”
Instead, the main intended use is “for early diagnosis where the antibodies haven’t come up yet or the antibody test is equivocal,” Liotta said.
Ceres also hopes to position the test for use in guiding antibiotic therapy, he said, the idea being that doctors could use it to monitor the presence of Borrelia in patient blood, keeping their antibiotic regimen going until they test negative for OspA.
“That [intended use] is very important for our next stage of development,” Liotta said.
Results from the JTM study suggest the potential usefulness of the test for such a purpose. Tracking a set of eight patients throughout antibiotic therapy, the researchers found that the test went from positive to negative as symptoms including the original rash disappeared with treatment.
While Ceres currently offers the test as an LDT, the ultimate goal is to take it through the US Food and Drug Administration, Petricoin said, adding that it plans to use the VBHRC funds to develop the multi-disease panel to the point where it could begin preparing an FDA submission.