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Lyme Disease Test Could Enable 15-Minute Results at the Point of Care

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NEW YORK – A rapid microfluidic blood test in development may detect early Lyme disease with sensitivity levels 30 percent higher than an approach laboratories use frequently to diagnose the condition.

A developer of the test Maria Gomes-Solecki, an associate professor at the University of Tennessee Health Science Center, said in an interview that the platform has potential to provide Lyme disease results in a doctor's office or hospital emergency room within 15 minutes. The test, which uses biomarkers routinely used in lab tests for the disease along with a custom biomarker in the microfluidic device, may provide an alternative to those lab tests, speeding up treatments for the condition and enabling diagnoses much earlier in the progression of the disease within the body, she said.

Gomes-Solecki, who is president of Memphis, Tennessee-based Immuno Technologies, a firm focused on applied research for infectious diseases, is developing the test in collaboration with a team led by Sam Sia, a professor of biomedical engineering at New York-based Columbia University.

The developers recently published findings of a National Institute for Allergy and Infectious Diseases (NIAID)-sponsored clinical study in the Journal of Clinical Microbiology, which evaluated use of the test to diagnose various states of Lyme disease in patients' serum. In the study, the test used three proteins that identified antibodies specific to B. burgdorferi, the bacterium that causes Lyme.

Gomes-Solecki and her colleagues evaluated and selected the most relevant antibody biomarkers, while Sia and his colleagues developed the current version of the microfluidic platform. Miami-based Opko Health provided microfluidic cassettes for use in the platform.

The test uses a benchtop analyzer to manage fluid flow, control temperature setpoints, and detect signals. A serum sample with gold-labeled secondary antibodies and silver amplification reagents are delivered automatically in sequence over five detection zones in a microfluidic channel. Sequential binding of sample antibodies, the gold-labeled detection antibodies, and the silver amplification reagent yield a visible signal that can be optically quantified and tied to the presence or absence of Lyme biomarkers.

To test the microfluidic device, the researchers obtained serum samples from NIAID. They tested 142 samples from patients with early Lyme disease, healthy individuals who live in areas endemic to the disease, and patients with Lyme arthritis.

Gomes-Solecki's team evaluated several biomarkers and selected the top three, VlsE lipoprotein and a proprietary synthetic 33-mer peptide (PepVF) to capture sensitivity in all disease stages, and outer surface protein C (OspC) for detection of early Lyme disease. Two of the biomarkers, VlsE and PepVF are used in existing Lyme disease laboratory tests and one, OspC, was custom developed for the test. The researchers shipped the antigens to Sia for incorporation into the Opko cassette and its subsequent integration into a microfluidic platform called mChip-LD.

The investigators found that the set of multiplexed biomarkers were more sensitive than a standard two-tier Lyme disease testing algorithm, while exhibiting high specificity. In identifying patients with early Lyme disease infection, just a few weeks from onset, the platform demonstrated a sensitivity 30 percent higher than the standard testing approach that includes testing with an enzyme immunoassay and subsequent use of a Western immunoblot assay, achieving 80 percent sensitivity overall, Gomes-Solecki said.

With specificity set at 95 percent, the sensitivity of mChip-Ld ranged between 80 percent and 85 percent for two panels used to test for early Lyme disease, and 100 percent for Lyme arthritis.

The developers anticipate moving the microfluidic test closer to commercialization with a subsequent clinical trial to further validate the device's performance in Lyme disease patients. Further, and depending on anticipated results emerging from the clinical trial, the group expects to enter discussions with the US Food and Drug Administration to ascertain what the agency requires to demonstrate the devices' analytical validity and clinical utility, Gomes-Solecki said.

A test available at the point of care may eliminate the requirement for trained and experienced personnel needed to run laboratory assays, reduce the time required to get a result associated with sending samples to a lab, and enable rapid patient treatment, she noted.

Opko has the right to commercialize the Lyme disease test on the new platform if the test's development and clinical results prove to be successful, Gomes-Solecki said. The firm did not respond to a request for comment.

The point-of-care test for Lyme disease, if successful, may need to be part of an approach that requires a second, separate lab test to confirm results, Chris Howard, chief commercial officer of Lyme disease test maker Zeus Scientific, said in an interview.

Howard, who is not involved in the development of the point-of-care test, said its development could "certainly be useful and many [developers] have contemplated getting [a test] nearer to the patient."

To avoid the recommendation of a second test, however, the developers would need to obtain approval from the US Centers for Disease Control and Prevention for a further change in its current testing algorithms for Lyme disease diagnosis, he said. Until recently, the CDC had recommended a single two-tiered enzyme immunoassay-igM/IgG Western immunoblot testing algorithm.

The agency developed the two-tier testing recommendation in 1994. Then, in 2011, researchers suggested that a modified approach, using two immunoassay tests and dropping the Western blot, would be an improvement.

Last year, the CDC altered its recommendations, allowing substitution of the Western blot assay and use of two enzyme immunoassays, as an additional, alternate approach to the existing two-tier algorithm.

On the back of that change, the FDA recently cleared four enzyme immunoassay tests marketed by Branchburg, NJ-based Zeus Scientific for use in the modified two-tier algorithm.

A number of groups are also looking to develop tests with higher sensitivities. Such tests include assays that detect active infections by identifying protein antigens, using PCR-based diagnostics, or employing next-generation sequencing.

Phoenix-based Translational Genomics Research Institute, for example, is developing a sequencing-based test, and Lexington, Massachusetts-based T2 Biosystems is developing the T2Lyme Panel based on its magnetic resonance technology through a partnership with Rockville, Maryland-based Canon US Life Sciences.   

Among companies offering products to laboratories, San Diego-based Quidel is marketing an FDA-cleared Lyme assay running on its Sofia 2 Fluorescent Immunoassay Analyzer.

Adriana Marques, an author of the JCM study and a scientist at NIAID, said that a test used in doctor's offices would result in better patient management.  

The types and sequence of tests that need to be implemented depend on the context of the disease; how the disease manifests itself in the body; its progression; and how the immune system responds, she noted.

"Very early on, you don't have time to develop antibodies, and tests are more likely to be negative," she said. "We know that the IgM portion of the Western blot has a lot of issues and in that early time of the infection, [less than 30 days from onset], when it is meant to be implemented, it really does not help much."

Marques said that a point-of-care test, that along with other tests increases the sensitivity of testing for early Lyme disease, has a potential as part of the modified two-tiered testing algorithm, which she previously described in JCM. Additionally, she said that such a point-care-test can be especially valuable to clinicians trying to decide whether a patient has Lyme disease or another condition and wants greater confidence prior to quickly prescribing an appropriate therapy.