This story has been updated to include comments from a company official.
The National Institutes of Health has awarded Akonni Biosystems nearly $3 million to develop an array-based portable system to help diagnose and survey Mycobacterium tuberculosis.
The assay is being designed to identify genetic markers associated with susceptibility to the antibiotic drugs rifampin and isoniazid by screening for the most common mutations in the rpoB, katG, and inhA genes. The test will also differentiate between M. tuberculosis and M. avium, the company said.
Akonni was notified of the grant this week. The funding amount for the first year is $2,985,932. The grant budget's end date is set as Aug. 31, 2013.
Kevin Banks, Akonni's vice president of marketing and sales, told BioArray News this week that the new grant was received in one lump sum that will fund the project over the next three years. Frederick, Md.-based Akonni received a $435,000 Small Business Innovation Research grant in June that was "primarily [for] developing a sample-to-answer system" for multi-drug resistant TB, or MDR-TB, Banks said. The US Centers for Disease Control and Prevention also awarded Akonni $100,000 in 2005 and $750,000 in 2006 to support the project, Banks added.
According to the grant's abstract, Akonni plans to use the latest funding to help it develop its prototype MDR-TB PCR TruArray by expanding test coverage, completing the manufacturing scale-up for future kits, and performing pre-clinical verification experiments.
A "significant portion" of the project is aimed at extending Akonni's array marker set to provide coverage for extensively drug-resistant TB, or XDR-TB, a subset of MDR-TB that is "resistant to any fluoroquinolone drug and at least one of three second-line injectable drugs [such as] amikacin, kanamycin, or capreomycin," Banks said.
In addition to expanding the coverage of the company's array, the grant advances the MDR/XDR-TB system in several other ways, Banks said. One is to transition from an open-amplicon system to a closed-amplicon system, which will "make the workflow easier to implement in international reference centers." Another is to "develop the necessary quality system infrastructure around the MDR/XDR-TB PCR array to enable clinical trials and CE marking for the product."
As part of the project, Akonni plans to verify isolates and amended sputum samples at the Wadsworth Center Laboratory of Clinical Mycobacteriology in New York prior to deployment. Akonni said in the grant abstract that it envisions deploying the system in regions where TB is most prevalent, including US border counties and South Africa. Banks noted that Akonni has a partnership with the South African Medical Research Council, which is headquartered in Capetown.
TB, Bacteria Menu
Seven-year-old Akonni already advertises MTB-TruArrays on its website for use with its internally developed, colorimetric-detection-based TruDiagnosis system. Banks said that initial array is the result of the earlier CDC funding and has been available to early adopters since last year.
Akonni offers a menu of other assays for research purposes that are designed to detect herpes, methicillin-resistant Staphylococcus aureus, and other bacteria. In addition, the company has an ongoing partnership with researchers at the University of California, San Francisco, to develop a portable system that can detect category A-C biodefense pathogens (BAN 9/7/2010).
Akonni claims its assays have a processing time of between 15 minutes and three hours, depending on the application. It is this relatively quick turnaround time that Akonni sees as its advantage in the market for TB tests.
"Culture-based methods remain the gold standard for diagnosing drug-resistant TB, but M. tuberculosis has a doubling time of 15 to 20 hours, which means that culture-based diagnosis, let alone drug-susceptibility testing, can require several weeks," Akonni noted in the abstract. "The genetics of MDR-TB, however, pose a problem for PCR, molecular beacon, or line-probe tests, because the extent of known drug-resistance signatures greatly exceeds the multiplexing capacity of conventional PCR assays."
Akonni said that by combing a multiplexed array with the sensitivity of PCR, configured as an entirely closed-amplicon test, and with a small technology footprint and low price point, array-based molecular diagnostics could be used in "low-resource settings" where TB is most prevalent.