Exosomes – tiny biological nanoparticles which transfer information between cells – offer significant potential in detecting and treating disease, the most comprehensive overview so far of research in the field has concluded.
Areas which could benefit include cancer treatment and regenerative medicine, say Dr Steven Conlan from Swansea University, Dr Mauro Ferrari of Houston Methodist Research Institute in Texas, and Dr Inês Mendes Pinto from the International Iberian Nanotechnology Laboratory in Portugal. 
Exosomes are particles produced by all cells in the body and are from 30-130 nanometres in size – a nanometre is one-billionth of a metre.  They act as biological signalling systems, communicating between cells, carrying proteins, lipids, DNA and RNA.  They drive biological processes, from modulating gene expression to transmitting information through breast milk.
Though discovered in 1983, the full potential of exosomes is only gradually being revealed.  The researchers show that the nanoparticles’ possible medical benefits fall into three broad categories: 

• Detecting disease – by acting as disease-specific biomarkers
• Activating immune responses to boost immunity
• Treating diseases  – serving as the vehicle for drugs, for example bearing cancer therapies as their payload, to target tumours

One of the most useful properties of exosomes is that they are able to cross barriers such as the plasma membrane of cells, or the blood/brain barrier.  This makes them well-suited to delivering therapeutic molecules in a very targeted way.
The potential benefits of exosomes can be seen in the wide range of research projects – cited in the paper – already either completed or under way, in areas such as:

• Improved testing for prostate cancer 
• A small-cell lung cancer trial
• Stem cell-derived exosomes strengthening heart muscles
• Regeneration of muscle and tissue
• Parkinson’s
• Diabetes

The team caution that there is more to do before research into exosomes translates into new techniques and treatments.  Side-effects need to be considered, and a standardised approach to isolating, characterising and storing exosomes will need to be developed. 
Researchers will also need to ensure that the properties of exosomes do not end up causing harm: for example they can transfer drug resistance and pacify the immune system.
Nevertheless, the potential is very clear, with the team describing exosomes as “increasingly promising”.
Professor Steve Conlan of Swansea University Medical School, one of the authors of the paper, said:
“Our survey of research into exosomes shows clearly that they offer enormous potential as a basis for detecting and treating disease. 

Swansea University
www.swansea.ac.uk/media-centre/latest-research/tinynanoparticlesoffersignificantpotentialindetectingandtreatingdisease-newreview.php

Researchers have found a specific type of immune regulatory cells that could soon be used as potential clinical biomarkers to diagnose certain autoimmune diseases.
The team from Instituto de Medicina Molecular (iMM) Lisboa, led by Luis Graça, analysed blood samples from Sjögren syndrome patients, an autoimmune disease that affects the mucous membranes and moisture-secreting glands of the eyes and mouth, and found that these patients have a significant increase in a specific type of immune cells called T follicular regulatory cells (Tfr). 
These cells are usually found in lymphoid tissues where they regulate antibody production. It was a surprise to find an increase of these type of cells in patients with excessive antibody production. In fact, the results were the opposite of what the team was expecting.
To understand the reason behind such unexpected results the researchers studied different biological samples. For instance, comparing Tfr cells in the blood and in the tissues where antibodies are produced (tonsils obtained from children subjected to tonsillectomies), provided evidence that blood Tfr cells are immature, not able to fully suppress antibody production. Such immaturity was confirmed by studying blood samples from other patients with genetic defects. Furthermore, exposure of healthy volunteers to flu vaccine led to an increase in blood Tfr cells, in line with their generation during immune responses with antibody production.
Blood circulating Tfr cells are distinguished from other circulating lymphocytes by two molecular markers, CXCR5 and FOXP3, the first of which endows these cells with the ability to migrate into specific zones of lymph nodes where they may complete maturation and regulate antibody production.
The team is now trying to understand what happens to these cells in other autoimmune diseases to evaluate their potential not only for diagnostic but also to identify which patients may benefit with medicines that interfere with the production of harmful antibodies.

Instituto de Medicina Molecular (iMM) Lisboa
imm.medicina.ulisboa.pt/en/imm-lisboa/news/archive/novo-tipo-de-celulas-do-sangue-funcionam-como-indicadores-de-doencas-autoimunes/

Health scientists at the University of Leicester and University of Nottingham have heralded the discovery of a gene associated with lung fibrosis as ‘a potential new avenue of treatment for further research into this terrible disease.’
Idiopathic Pulmonary Fibrosis (IPF) is a debilitating lung disease, affecting ~6,000 new people each year, where scarring (fibrosis) of the lungs makes it difficult to breathe.
IPF, on average, results in death 3 years after diagnosis. There is no cure for IPF, and currently available drugs can only slow the disease down, and do not stop, or reverse, it. Furthermore, some patients may suffer unpleasant side-effects. A better understanding of the disease is needed to develop even more effective treatments.
Researchers Professor Louise Wain from the University of Leicester and Professor Gisli Jenkins from the University of Nottingham were lead authors of the study.  They analysed the DNA from over 2700 people with IPF and 8500 people without IPF from around the world and found that people with IPF are more likely to have changes in a gene called AKAP13.
The researchers were also able to show that these DNA changes affect how much AKAP13 protein is produced by the gene in the lungs.  Researchers know from other studies, that AKAP13 is part of a biological pathway that promotes fibrosis (or scarring) and importantly that this biological pathway can be targeted with drugs. Taken together, the findings suggest targeting this pathway with drugs in people with IPF might lead to new treatments. To confirm this, the research team now need to undertake more detailed studies into the role of AKAP13 in people with IPF.
The work was led by researchers at Leicester and Nottingham and brought together collaborators from around the world to form the largest combined analysis of people with IPF undertaken to date.

Leicester University
www2.le.ac.uk/offices/press/press-releases/2017/october/leicester-and-nottingham-scientists-discover-new-gene-associated-with-debilitating-lung-disease

An international team of researchers has identified genomic mutations for Carey-Fineman-Ziter (CFZS) syndrome, a very rare congenital myopathy (inherited muscle disorder) characterized by facial weakness, a small or retracted chin, a cleft palate and curvature of the spine (scoliosis), among other symptoms. The researchers determined that CFZS is caused by mutations in the gene MYMK that encodes for the protein myomaker. This protein is necessary for the fusion of muscle cells (myoblasts) into muscle fibres (myotubes) during the development of an embryo and the regeneration of muscle cells after injury.
"Advances in genomics technology and the power of team science have enabled us to identify the cause of this very rare disease 35 years after it was first described by Dr. John Carey and colleagues from the University of Utah," said National Institutes of Health Director Francis S. Collins, M.D., Ph.D., a co-author of the study.
"This discovery will improve physicians’ ability to diagnose this disease and offer families accurate genetic counselling and treatment," said Irini Manoli, M.D., Ph.D., co-lead author and a physician scientist and staff clinician in the Medical Genomics and Metabolic Genetics Branch at the National Human Genome Research Institute (NHGRI), part of NIH. People affected with CFZS have sometimes been misdiagnosed with Moebius syndrome, another very rare disorder characterized by facial paralysis.
Dr. Manoli said that uncovering that cell-cell fusion deficits can lead to congenital myopathies (inherited muscle disease) opens a new path of exploration for therapies for CFZS and other muscular diseases and tools for regenerating muscle. "In addition," she said, "this rare genetic syndrome provides novel insights into the effects of muscle development on craniofacial and skeletal bone formation."
The goal of the study was to learn more about the genetics and clinical characteristics of Moebius syndrome and other congenital facial weakness disorders. Toward this end, the consortium brought 63 people to the NIH Clinical Center affected with Moebius syndrome and other inherited facial weakness disorders, and their families for detailed multi-system evaluations, including brain and muscle imaging studies and muscle biopsies. The researchers collaborated through the Opportunities for Collaborative Research at the NIH Clinical Center, a new funding mechanism that encourages intramural and extramural researchers to work together at the NIH Clinical Center.
Researchers performed detailed phenotyping (identifying physical traits that are the result of a DNA sequence). They also employed the most up-to-date genomic tools, including exome sequencing of blood DNA in affected siblings from three unrelated families, as well as a muscle biopsy in one of the affected individuals. To identify the genomic mutations associated with CFZS, three laboratories – led separately by Elizabeth Engle, M.D., at the Boston Children’s Hospital, Stephen Robertson, M.D., from the University of Otago and John Carey, M.D., at the University of Utah – analysed exome sequence data from each of the three families. Among the genes harbouring mutations identified in each family, only the gene MYMK was common to all three. A knockout mouse model (genomically altered mice that are bred to lack a specific gene) displayed a complete lack of muscle development, leading to early death of the newborn mice, making this gene a promising candidate for further studies.
Using CRISPR-Cas9 technology, a tool for editing DNA at precise locations, a team led by Silvio Alessandro Di Gioia, Ph.D., and Dr. Engle, generated zebrafish with a mutated mymk gene. Affected mutant zebrafish were smaller and had abnormal muscle development and jaw deformities, resembling the patient phenotype. The researchers then performed further functional studies to validate the severity of each of the genomic mutations.
The researchers were able to correct affected zebrafish’s muscles by injecting the normal human MYMK gene product into the mutant fish. This success lends hope for restoring MYMK function in muscles as a treatment for CFZS and for reducing any potentially progressive features of this disorder.
Only eight people in the world have been diagnosed with CFZS with MYMK mutations, in part, because it hasn’t been readily recognized. Now that researchers have identified the genomic cause underlying the syndrome, it can be added to the diagnostic gene panels for congenital myopathies. This will improve the speed and accuracy of diagnosis and add to the understanding of the spectrum of disease severity and outcome, Dr. Manoli said.

The National Human Genome Research Institute (NHGRI)
www.genome.gov/27568961/2017-news-release-nih-and-collaborators-identify-the-genomic-cause-for-careyfinemanziter-syndrome/

Siemens Healthineers has entered into a definitive agreement to acquire Epocal Inc., a subsidiary of Alere Inc. Epocal Inc. develops and provides point-of-care blood diagnostic systems for healthcare enterprises, including the epoc Blood Analysis System, a handheld, wireless testing solution. Financial details of the transaction are not being disclosed. The transaction is subject to the completion of Abbott’s acquisition of Alere, as well as antitrust approvals and other customary closing conditions.
“We want to help our customers innovate care delivery. As one of the market leaders in blood gas, the acquisition of the epoc product line will enable us to provide the right solution in the right setting, all from one partner,” said Peter Koerte, President, Point of Care Diagnostics, Siemens Healthineers. “The epoc product line will seamlessly integrate with our digital ecosystem offering customers the broadest solution available in the market. The acquisition complements our existing offerings in the point of care diagnostics space, with a view to provide customers globally with a full range of blood gas solutions.”
Healthcare systems continue to look for ways to elevate patient experience and satisfaction as well as the quality of care. It is a strategic goal of Siemens Healthineers to support healthcare providers worldwide to meet their challenges and excel in their respective environments. Health networks may have varying testing needs near to their patients at the point of care in physician’s offices, clinics, emergency departments and labs. With a complete offering for blood gas diagnostics from a low-volume, single-use handheld device up to a high-volume, multi-use benchtop solution, Siemens Healthineers can help customers improve their workflows and utilize the correct system for the needs of their particular settings.
Arterial blood gases are an important routine investigation to monitor the acid-base balance of patients. They play an important role in the work-up and management of critically ill patients and may help in diagnosing pulmonary and metabolic disorders. They indicate the severity of a condition and help to assess treatment. Blood gas test systems are an important component in critical care settings such as hospitals, clinics, emergency departments and pulmonary laboratories.
The epoc Blood Analysis System is a handheld, wireless testing solution that provides blood gas, electrolyte and metabolite results near the patient in approximately 30 seconds after sample introduction. The epoc Blood Analysis System is comprised of the epoc room-temperature stable BGEM test card, epoc reader and epoc host2 mobile computer. Each single-use epoc BGEM test card features smartcard technology with a full menu of tests on one card.
www.siemens.com/healthineers