VIENNA, Austria—Worldwide, the number of osteoporotic fractures is just under 10 million per year. Osteoporosis has become a major socioeconomic challenge that burdens patients as well as public and private health insurers. Based on the steady increase in life expectancy, the incidence of osteoporosis will continue to rise. Tools for early diagnosis and targeted therapeutic intervention can counteract this trend.
TAmiRNA, a biopharmaceutical research and development company spun off from the University of Natural Resources and Life Sciences in Vienna, presented the new osteomiR molecular diagnostic test kit for the detection of osteoporosis at the American Society for Bone and Mineral Research (ASBMR) 2016 Annual Meeting in Atlanta, Georgia, in September. The company develops biomarker solutions aimed at improving detection of serious age-related illnesses such as osteoporosis.
“Due to the heterogeneity of osteoporosis, we are convinced that early and personalized diagnosis are essential for a timely and successful therapeutic prevention of bone fractures, which are associated with great pain, immobility and unfortunately even mortality,” said Matthias Hackl, director of the osteomiR program and co-inventor of the microRNA based diagnostic procedure.
He added, “Low-energy fractures are the hard clinical endpoint of osteoporosis. Doctors require sensitive and specific diagnostic tools to capture fracture-risk early and initiate preventive interventions on the basis of exercise, diet or therapeutic treatment. Currently, the gold-standard technology for diagnosing osteoporosis and fracture-risk is bone densitometry (DXA), which measures bone mineral density (BMD). However, BMD is considered to lack sufficient specificity and sensitivity for early diagnosis of fracture risk from osteoporosis, because 50 percent of women with low-energy fractures do not have osteoporotic bone mineral density, according to the WHO [World Health Organization] definitions. In addition, the availability of DXA is limited in some countries.”
Since 2013, TAmiRNA has been developing a minimally invasive molecular diagnostic test to estimate fracture-risk in postmenopausal women, as well as other subgroups at risk of osteoporosis. The results of the clinical development, which have been published in peer-reviewed journals in 2015 and 2016, show that serum concentrations of specific microRNAs are significantly associated with osteoporosis and the risk of fractures. Using multivariate diagnostic algorithms, a significant improvement of the classification performance of bone densitometry and other risk scores can be achieved, according to Hackl.
The osteomiR kit has been developed to standardize both laboratory and data analysis of these microRNAs (“osteomiRs”) in patient serum samples. For now, the osteomiR kit is for research-use only, but in the near future, the clinical utility of it will be investigated in multiple clinical research centers for musculoskeletal disease.
The osteomiR biomarker is a blood-based molecular diagnostic test to diagnose fracture risk. The information contained in the blood-based biomarkers significantly outperforms DXA/BMD, according to Hackl. In addition, he said, the osteomiR biomarker test is easy to scale up, because blood samples can be shipped longer distances to centralized testing laboratories.
As Hackl explained, microRNAs are a class of non-coding RNA molecules that regulate gene expression and correct cell function. Abnormal microRNA expression can be a consequence or cause of the onset and progression of disease. Because microRNAs are constantly released from cells through specific mechanisms, their composition in blood changes during disease development. “On the basis of several studies in more than 1,000 patients, we were able to show that certain microRNAs are strongly associated with the progression of osteoporosis and the risk of fractures. From these data, we were able to develop diagnostic algorithms based on microRNAs and clinical parameters to allow a more accurate patient classification,” said Johannes Grillari, professor at the University of Natural Resources and Life Sciences and a co-founder and scientific advisor of TAmiRNA.
Hackl added, “TAmiRNA is specialized in biomarker development using blood-circulating microRNAs [which] are evolutionary conserved regulators of gene expression and cell/tissue function. MicroRNAs that are transcribed in blood cells but also peripheral tissues can be detected in liquid biopsies such as serum, plasma or urine. Changes in microRNA serum levels can be indicative of physiologic changes in a tissue and therefore can be applied to diagnose the onset and progression of a disease. The osteomiR test is a diagnostic algorithm that interprets information from up to 10 serum microRNA levels as well as clinical parameters. Based on this algorithm, the osteomiR test reports a new fracture-risk score for each patient. This score will provide decision support to doctors, clinical researchers and pharmaceutical companies that manage osteoporotic patients or develop anti-osteoporotic drugs.”
TAmiRNA is attempting to obtain certification for the osteomiR test as a CE-IVD test in Europe, Hackl said. “For this purpose we will conduct clinical evidence studies in 2017/18 to obtain CE-IVD marking in in Europe by the end of 2018,” he added.
“Health economic models have shown that by significantly improving early diagnosis of osteoporosis we can reduce the number of fractures and increase quality-adjusted life years (QALYs) in the central European population,” Hackl concluded. “Based on this important impact, we believe that the osteomiR device has huge financial potential.”