Small RNAs with First Clinical Impact

Small RNAs are about to make their clinical debut. This week, Asuragen, a leading microRNA diagnostics and therapeutics company, announced that it is about to launch the first microRNA-based diagnostic test for the differentiation between chronic pancreatitis and pancreatic ductal adenocarcinoma (PDAC). PDAC is the most prevalent pancreatic cancer type and known for its late clinical presentation and poor prognosis. Because chronic pancreatitis that has a roughly comparable incidence and presents with often similar symptoms such as abdominal pain, digestive problems, and biliary obstruction resulting in mis-diagnosis rates of up to 25%, diagnostics that help to differentiate between them are invaluable for ensuring optimal treatment.

The test will be made available on May 2, 2008, from Asuragen’s own CLIA-certified test laboratory. It is a PCR-based test of apparently a single microRNA that is specific for pancreatic cancer cells and was originally identified as part of a collaboration between Asuragen and a clinical group from a hospital in Bochum, Germany [Szafranska et al. MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene 26:4442-52 (2007)].

Other tests by Asuragen, but also notably Rosetta Genomics and Exiqon in the field, are about to enter the market in the coming months. Like the present one, they are PCR-based diagnostics of one or a few microRNAs. Despite the 25% mis-diagnosis rate, it seems that the need to obtain biopsies from the pancreas is not trivial and may therefore limit the use of this particular test. Tests which may diagnose a cancer based on microRNAs isolated from blood samples, and are currently under development, should have wider applicability, although this may be at a rather late stage of cancer.

Asuragen is a private company and it has been therefore more difficult for me to follow their progress. The fact that they beat the publicly held Rosetta Genomics and Exiqon in bringing the first microRNA diagnostic to market is likely based on their heritage of having been spun-out from the RNA research reagents company Ambion (now an Applied Biosystems subsidiary), therefore giving them prime access to very relevant technologies and know-how. The fact that they operate a CLIA-certified laboratory, of course, may be another significant efficiency giving them an advantage over its competitors. Ultimately, however, it would appear that the commercial success will depend on their ability to make the test widely available through larger diagnostics distribution partners. Alternatively, microRNA diagnostics that are tied to certain drugs, such as Rosetta’s squamous versus non-squamous non-small cell lung cancer (NSCLC) Dx that ensures that Genentech’s Avastin is not used for squamous NSCLC, could benefit from the marketing reach of large therapeutics partners.

At any rate, the fact small RNAs are about to have a real clinical impact less than a decade after their widespread occurrence in biology was first recognized, is to be celebrated and indicates that their small size and stability, and their biological involvement in disease makes them a very promising class for molecular diagnostics.