NEW YORK (GenomeWeb) – Vienna-based TAmiRNA has developed a test employing a microRNA signature for early detection of osteoporosis, and is preparing for multi-center clinical trials in Europe and the US with a view to submitting a blood-based test for CE marking in 2018 and launching it for clinical use in Europe later that year.
Multiple studies in more than 1,000 patients have shown that specific microRNAs are strongly associated with the progression of osteoporosis and the risk of fractures, according to TAmiRNA. The firm said that to improve the accuracy of fracture risk scores for patients with osteoporosis, its test combines multivariate diagnostic algorithms based on serum microRNA levels with clinical parameters such as age and bone mineral density.
TAmiRNA used its technology to develop a test kit, OsteomiR, that it launched for research use last week at the annual meeting of the American Society for Bone and Mineral Research in Atlanta. The firm said that in the near future it will investigate the clinical utility of the test for musculoskeletal disease in multiple clinical research centers.
Abnormal microRNA expression can be a consequence of the progression of disease, or it can be a cause of its onset, according to Matthias Hackl, director and co-founder of TAmiRNA. Changes in the composition of blood-based microRNAs as the disease develops enabled the firm to reflect these changes as measures of bone fracture risk.
"Standard tests for osteoporosis that measure bone mass or microarchitecture, as well as more advanced tests that employ single biomarkers, are challenged in generating successful therapeutic outcomes because of the heterogeneous nature of the disease," Hackl told GenomeWeb. "Different patients present with very different levels of risk."
The gold-standard in testing for osteoporosis is bone densitometry, or DXA, and researchers have reported that more than half of the older women who sustain a fragility fracture do not have osteoporosis as defined by World Health Organization (WHO) bone mineral density criteria.
"An early, personal diagnosis is needed for more timely and successful prevention of bone fractures," Hackl said. "And an accurate test is needed that classifies the patient population according to level of risk."
At the ASBMR meeting last week, clinical researchers at TAmiRNA presented unpublished data from a longitudinal study involving 170 patients with type 2 diabetes that they tested for bone fracture risk. Since 2015, the researchers have been studying circulating microRNAs, or combinations of microRNAs, that could best characterize the fracture risk for different patient groups, including women who are postmenopausal and have type 2 diabetes, as well as men. In one of its studies, eight miRNAs -- miR-152-3p, miR-30e-5p, miR-140-5p, miR-324-3p, miR-19b-3p, miR-335-5p, miR-19a-3p, miR-550a-3p -- were found to be good discriminators of patients with low-traumatic fractures, regardless of age and gender.
Using microRNA qPCR arrays, they were able to characterize the risk of fracture associated with individual microRNAs and combinations of them with high specificity and sensitivity, the firm said.
To demonstrate the economic value of improving fracture-risk assessment, TAmiRNA engaged in a Horizon 2020 EU-funded project to assess the cost effectiveness of the osteomiR test for a central European population. The results of the project will be presented soon during a meeting of the International Society for Pharmacoeconomics and Outcomes Research in Vienna, according to TAmiRNA, and the findings show that fracture-risk assessment using microRNAs is a cost-effective alternative to DXA and to no monitoring.
Hackl, a co-inventor of the microRNA-based diagnostic procedure, founded the company with Johannes Grillari, a professor at the University of Natural Resources and Life Sciences, as a spinout from the Vienna-based university.
Hackl said that they launched the company with the objective of promoting the discovery and development of microRNAs as tools for diagnosis and treatment of age-related diseases, including not just osteoporosis but also neurodegenerative diseases, and it has plans to develop a diagnostic test for cardiovascular disease using microRNA signatures. A common theme of the research work, he said, is to advance early-risk assessment of age-associated diseases.
TAmiRNA is currently investigating the clinical utility of the fracture risk test in multiple clinical research centers. It expects to offer the fracture risk test for around €100 ($112) so that it is competitive, on average, with competing bone densitometry tests. Worldwide, almost 10 million osteoporotic fractures occur each year, according to TAmiRNA.
Although the roadmap for US Food and Drug Administration clearance in the US is less clear, Hackl said, the company has plans to submit its bone fracture test for pre-market approval after submitting for CE marking in Europe.
Hackl said that although there are genome-wide association studies that link genomic research to osteoporosis and bone fracture risk, he was not aware of other companies offering molecular diagnostic tests for this application.
For example, in January, researchers from Decode Genetics and elsewhere described new genetic variants that appear to coincide with both bone mineral density (BMD) in the spine and risk of osteoporotic fractures. The results also uncovered a new BMD-related gene, PTCH1, as well as a previously undescribed variant in a gene with prior ties to BMD called RSPO3. The results were confirmed in nearly 10,100 more individuals with European or East Asian ancestry.
Another study led by researchers from the University of Cambridge that involved nearly 70,000 women linked more than 40 regions of the genome to a woman's age at menopause. The study noted that earlier menopause has been linked to a lower risk of breast cancer, but a higher risk of osteoporosis, cardiovascular disease, and type 2 diabetes.
And in 2015, researchers reported identifying a low-frequency noncoding variant associated with large effects on bone mineral density. The researchers led a project, UK10K, to sequence 10,000 individuals and published their initial results in Nature Communications. The publication highlighted the utility of using the combined whole-genome and exome UK10K data, as well as a genotype reference panel.