NEW YORK (GenomeWeb) – MNG Laboratories has been expanding its catalog of next-generation sequencing-based molecular tests as a complement to its biochemical assays in order to improve the diagnosis of rare inherited disorders, in particular neurological diseases.
Last month, the Atlanta-based company, which has about 40 employees, launched several diagnostic RNA sequencing tests. It is also developing a whole-genome test, as well as a methylome test to detect the causes of imprinting disorders. In addition, a year ago the lab started offering an exome carrier screening test after realizing that many of the diseases it diagnosed in patients would not have been picked up by conventional carrier testing in their parents.
The privately owned company started in 2001 as Horizon Molecular Medicine. It was rebranded in 2008 as Medical Neurogenetics and now does business as MNG Laboratories. In 2015, HealthEdge Investment Partners, a private equity firm, funded the company with an undisclosed amount to drive its continued growth.
In early 2016, MNG brought in Peter Nagy as its laboratory director and chief medical officer, and Terry Conrad as CEO and president. Nagy joined the firm from Columbia University Medical Center, where he was the director of clinical NGS in the Laboratory of Personalized Genomic Medicine and helped to launch several NGS-based diagnostic tests, such as an exome test for inherited disorders and a cancer exome and transcriptome assay. Also in 2016, MNG's laboratory received CAP accreditation.
Earlier this month, MNG appointed Humberto Huerta as senior director of business development. He joined the company from Cynvenio Biosystems and previously worked for Ambry Genetics. In addition, MNG added five new members to its scientific advisory board last week.
According to Conrad, MNG's specialty lies in neurogenetics and includes both molecular and metabolic testing. The company has amassed a neurogenetic database that includes more than 15,000 cerebral spinal fluid samples its lab has analyzed, and it has conducted more than 10,000 NGS tests.
"The philosophy of our lab has really been that we'd like to cover all aspects of neurogenetics," said Keith Hyland, MNG's executive VP, who has been with the company since 2004 and has developed many metabolic tests for it, for example to measure neurotransmitters in cerebrospinal fluid.
Metabolic testing still generates most of the test volume, Conrad said, and is a business that has been stable or slightly growing in recent years. "We see growth potential from that area in working with pharma and biotech clients as they do drug development," he said, especially in conjunction with the company's database.
NGS-based tests, while lower in volume, are typically higher in price, and MNG has seen "really good growth" of that business, he said.
The company currently does not rely on reimbursement from health insurance for its revenues, as it bills customers directly, but Conrad said he expects that to change in the future. "Right now, that's not part of our business model," he said.
MNG does not have many competitors with a similar focus on neurogenetics but it faces competition from large genetic testing labs like GeneDx, Ambry Genetics, EGL Genetics, PreventionGenetics, and Blueprint Genetics.
Most of the company's testing business currently comes from the US, typically from children's hospitals and university centers, though it also conducts tests for reference labs. MNG also has "a very solid business" in Canada, Conrad said, and it receives patient samples from all over the world, including the Middle East and Asia.
Overall, the company has found that results from metabolic and molecular tests often go hand in hand, providing different pieces of the diagnostic puzzle.
"If we find abnormalities in a [metabolic] pathway, then we can look at the [gene] panels that are associated with that pathway and look for genetic defects," said Hyland. "And in the reverse manner, if we find variants of unknown significance and we have biochemical or enzymological indicators about a particular gene, then we can go back to the biochemistry and say 'that's abnormal' and determine whether that VUS may actually be a pathogenic variant."
For example, the lab often diagnoses pyridoxine-dependent epilepsy by analyzing spinal fluid from children with seizures of unknown origin for metabolites. It subsequently often finds pathogenic mutations in the ALDH7A1 gene, which causes PDE.
Another example is the DDC gene, which encodes the enzyme aromatic L-amino acid decarboxylase. MNG has detected almost 30 different variants in that gene in patient samples, about half of which were initially variants of unknown significance. The lab also had spinal fluid metabolite data for these patients, as well as data from a plasma-based enzymatic assay. "And when we correlated all of the data, virtually all of the VUS-es turned out to be pathogenic," Hyland said, adding that the company is currently preparing the results of this analysis for publication.
On the molecular side, MNG offers both diagnostic and carrier screening tests, with turnaround times between two and four weeks. The lab is equipped with two Illumina HiSeqs and one MiSeq sequencer and plans to purchase a NovaSeq.
Diagnostic tests include more than 100 phenotype-directed gene panels, mitochondrial genome sequencing, exome sequencing, three recently launched RNA sequencing tests, and Sanger-based single-gene tests. In addition, repeat expansion testing is available for certain disorders.
All molecular test results for the same patient are returned in a single report, and pricing for those tests is bundled, which Nagy said is a unique aspect of MNG. "We try to give you an answer rather than send you disconnected reports," he said.
MNG also offers three carrier screening tests: an Ashkenazi Jewish carrier screening panel, a pan-European carrier screening panel, and the MNG Carrier Exome. The carrier exome test, which has a list price of $5,500, only reports results that put a couple's offspring at risk, not the individual carrier status of the two partners. According to Nagy, it is designed for couples with an uncertain or poorly characterized ethnic background who worry that other carrier screening tests might miss mutations that are specific to their family or background. For customers wanting their own carrier status, or genetic risk variants relevant to their own health, the company offers the MNG Healthy Exome, which has a list price of $2,995. For both types of exome tests, MNG only reports known pathogenic or likely pathogenic variants, Nagy said, and only for selected conditions.
The reason the company developed the carrier exome test was that about 60 percent of significant neurological conditions it diagnosed in patients that resulted from homozygous or compound heterozygous mutations would have been missed by traditional carrier screening. "That inspired us to offer this whole-exome approach," Nagy said.
MNG also makes sure its molecular test results are based on the most recent findings. Its internal reference database gets updated monthly, Nagy said, based on new releases from the ClinVar resource, and the lab's custom capture design gets updated every four to six months to incorporate new results.
Starting early next year, MNG also plans to contribute variants from its own tests to ClinVar, following a planned publication of results from its internal data.