"A breakthrough study led by the University of Sydneys Brain and Mind Centre and Royal Prince Alfred Hospital has revealed unique molecules in the blood of people with Multiple Sclerosis MS that could become definitive diagnostic biomarkers of the worlds most common neurologic disability in young adults. Published today in Scientific Reports the discovery identifies tiny dysregulated microRNA molecules that correctly diagnose MS and discriminate between patients at different disease stages  all in a simple blood test. Currently there is no definitive test for MS. Diagnosis and disease monitoring relies on several parameters including clinical examination MRI cerebrospinal fluid assessment and electrophysiology.  MS is a chronic disease so current diagnostic and monitoring tests are costly and still have limited utility to discriminate between different stages of the disease.  Key findings In addition to identifying biomarkers that distinguish healthy people from those with MS the researchers identified nine unique microRNA molecules that differentiate between two MS subtypes relapsingremitting MS RRMS and progressive MS. Relapsingremitting MS RRMS affects  percent of people and often evolves into a secondary progressive form of MS.  percent of people with MS are diagnosed with a progressive form of the disease from the outset known as primary progressive MS. The team also validated eight out of nine microRNA molecules in an independent group of progressive MS cases confirming the reproducibility of the findings. This is the first demonstration that microRNAs associated with circulating exosomes in blood are informative biomarkers not only for the diagnosis of MS but in predicting disease subtypes with a high degree of accuracy said Associate Professor Michael Buckland Head of the Department of Neuropathology at RPA Hospital and the Brain and Mind Centre University of Sydney.  The research was made possible through the generosity of patients at the Brain  Mind Centres multidisciplinary Multiple Sclerosis Clinic a collaborative service offered by Royal Prince Alfred Hospital and the University of Sydney. The research was funded by an Incubator grant from MS Research Australia. This blood test may allow people with MS to begin treatment earlier and identify the most appropriate treatment for their condition said Dr Matthew Miles CEO MS Research Australia.  This in turn may lead to fewer relapses and a slower loss of brain volume resulting in slowing or potentially halting progression of the disease for the person living with MS. It will also help remove the uncertainty surrounding which sub type of the disease an individual has and therefore be a catalyst for better outcomes for all people with MS. About the science Multiple Sclerosis MS is a chronic inflammatory demyelinating disease of the central nervous system CNS. The research team assessed the utility of microRNAs miRNA in serum blood exosomes as biomarkers of MS disease.  MicroRNA are small noncoding RNA that control many genes and processes vital for cellular life such as metabolism development and the immune system. They are called miRNA because they are very short only  letters long. Science has so far identified about  human miRNAs. Exosomes are nanosized particles shed by almost all cell types in the body and are packed with microRNAs and other types of small RNA. The research team has shown previously that some microRNAs are selectively packaged into exosomes for release from the cell.  Exosomes are tiny packages released by both healthy and diseased cells in the body. They circulate in blood and can be purified in their millions from a single vial of blood. Dubbed the biological equivalent of tweeting the exosomes circulate throughout the body and can deliver their cargo of information to multiple cells in almost realtime. In inflammatory diseases such as MS there is a significant increase in circulating exosome concentrations.  In studying the blood exosomes of healthy volunteers and patients with MS the research team identified a molecular signature of MS that not only correctly diagnoses MS but also discriminates between patients with different stages of disease Associate Professor Buckland said. Exosomes released by brain cells circulating in the blood so they offer an easily accessible way to monitor diseases of the brain. We are only now starting to wake up to their enormous potential as clinical tests. Given exosomes can cross the bloodbrain barrier it is likely that some of the circulating exosomes in MS patients come from affected central nervous system cells or the associated inflammatory milieu. The researchers hypothesised that physiological changes associated with MS and its progression is reflected in differences in serum exosomal microRNAs.  Using next generation sequencing and integrative bioinformatics they found that serum exosome microRNA profiles not only distinguish MS from healthy controls but also distinguish relapsingremitting MS RRMS from progressive MS with high accuracy. Associate Professor Michael Buckland is Head of the Molecular Neuropathology at the University of Sydney and Head of the Department of Neuropathology at Royal Prince Alfred Hospital."