The Peripheral Biomarkers special series, published in Alzheimer’s Research & Therapy, tackles the current issues surrounding the search to identify blood biomarkers for AD and discusses biomarker approaches that have already produced data that may help to advance the field.

Douglas Galasko, Director of the UCSD Shiley-Marcos Alzheimer’s disease Research Center, USA.

In this accompanying podcast, Alzheimer’s Research & Therapy In-house Editor Kathryn Smith talks to Series Editor Douglas Galasko about how attitudes towards biomarker studies have changed over the years, current exciting avenues of investigation and key questions in the field. Galasko also shares his thoughts on the future directions of biomarker research in AD.

Galasko is a neurologist at the University California, San Diego, USA, Director of the UCSD Shiley-Marcos Alzheimer’s disease Research Center and is also co-Editor-in-Chief of Alzheimer’s Research & Therapy. As Series Editor for the ‘Peripheral Biomarkers’ special series, Galasko brings together a collection of articles addressing a variety of topics, including; the potential of plasma amyloid beta (Aβ) as a biomarker, the use of biomarkers to evaluate the risk of incident AD, and novel approaches to biomarker discovery.

“In the 1980s we had a reasonable idea of the pathology of Alzheimer’s disease and yet this was not being used at all to make the diagnosis. So I was interested in trying to see whether the key pathological features of Alzheimer’s, namely plaques and tangles, would be reflected in something we could measure as a biomarker.”
Douglas Galasko, University of California, San Diego

Highlights of the series include a review by John Trojanowski and colleagues from the University of Pennsylvania School of Medicine, USA on plasma measures of Aβ, summarising a wealth of data on Aβ as a diagnostic and a predictive biomarker, as well as addressing the demographic, clinical, genetic and technical issues surrounding Aβ levels and measurement

In addition to covering the benefits and drawbacks of individual biomarkers, the series also takes a look at multiplex biomarkers in a review by Ralph Martins from Edith Cowan University, Australia and colleagues. The challenges faced by researchers in developing a global multiplex panel of biomarkers for AD are summarised and moreover potential solutions are outlined with the aim of advancing the field by reducing variability across studies.

Efforts to make progress in biomarker discovery have also led to studies into the body’s response to abnormal pathological proteins. Thomas Kodadek and Lorraine Fuhrmann Clark from the Scripps Research Institute, USA discuss key questions around the identification and screening of autoantibodies produced in response to various pathological features of AD.

Upcoming series content includes a review by Sudha Seshadri and Galit Weinstein from Boston University, USA discussing the candidates for potential use as circulating biomarkers that predict incident AD.

“There is great interest in biomarkers in general, and there have been many demonstrations of their value in approaches to diagnosis and therapy,” remarked Galasko in regards to the importance of peripheral biomarkers in AD. More on these advances and current issues faced in peripheral biomarker research for AD can be found in the ‘Peripheral Biomarkers’ special series.

The complete list of series articles:

Peripheral Biomarkers

What was your motivation for performing the study?
This research is mainly driven by the appreciation that miRNA is a rather stable component not only in serum but even more so in blood cells. Our study is conducted as part of a general endeavor towards the development of miRNA blood born biomarkers. Within this framework we set out to identify disease specific miRNA signatures.

What did you find most surprising about your results and what can  we learn from this?
Most intriguing is the disease specificity of the miRNA pattern found in blood cells of patients. At this point of our research we are only at the beginning of a biological understanding of the miRNA pattern identified. Similarities in some elements of the miRNA pattern between Alzheimer’s disease patients and those with other neurological conditions, possibly reflect similar biological processes in the cells harboring the miRNAs. Knowing the identities of the miRNAs present in blood biomarkers will allow us to gain insight into aspects of the immunological response, at least for those cell types that contribute most of the miRNA signatures.

How close to the clinic do you believe miRNA blood biomarkers for Alzheimer’s disease are?
Our results make us confident that miRNA signatures can likely play a role in the future diagnosis of Alzheimer’s disease. Prior to clinical studies it is however important to clarify the biological role of the identified miRNAs and to determine to what extent the miRNA pattern reflects different stages of the disease.

Do you believe it will ever be possible to sufficiently partition an Alzheimer’s disease signature from other cohorts to make miRNA blood biomarkers the sole basis of diagnosis?
To answer this question we need to deepen our understanding of the biology of the blood born miRNA signature. Independent of the progress in our understanding of the function of miRNAs in blood cells, it is however likely that miRNA signatures will mostly play a role as companion diagnostics.

What’s next for your research?
Our primary near-term goal will be to address the question about the diagnostic potential of miRNAs as early biomarkers.  Given the situation of Alzheimer’s as a progressive disease, it appears of foremost importance to identify those miRNA that indicate the disease in the early stages.

For more on the burden of Alzheimer’s disease and efforts underway to better manage and treat the disease, see our interview with Executive Director of Alzheimer’s Disease International, Marc Wortmann.

How did this research come about, and why is there a need for a tool to improve communication and palliative care in ICUs?

Communication and support for patients and their families are of central concern in healthcare. However, evidence shows that these are often poorly addressed, especially at times of rapid changes in health status and during clinical uncertainty. The Intensive Care Unit is a setting in which patients are profoundly ill and where their circumstances can change rapidly. Previous research has highlighted concerns in relation to support for patients and families, lack of adequate control of patient’s symptoms, inconsistent or lack of communication and attention to patients and families’ individual wishes and to dignity, respect and peace in the Intensive Care Unit. This led us to believe that there was a need to improve communication and palliative care in Intensive Care Units, and to develop a tool to try and achieve this.

What are the challenges associated with communication within an ICU setting?

The Intensive Care Unit is a highly challenging environment for patients and families. Patients are normally profoundly ill making communication very difficult. The nature of that illness and its severity means that it is often difficult or impossible to communicate with them directly – many are for example unconscious and in the process of being ventilated. Their families are entering a very unfamiliar place and are often in shock about what has happened and struggle to cope with this while supporting the patient as best they can. Although the central goal of the Intensive Care Unit is to preserve or extend life, the nature of illness or trauma means that sometimes this is not possible. Staff strive to actively treat the person’s illness, and support them, and seek to extend life. However, the severity of the illnesses that individuals face means that sometimes this is not possible. Things can change quickly, and there is a lot of information for families to take in.

What is the PACE tool and how does it work?

PACE stands for psychosocial assessment and communication evaluation. The goal of developing this tool was to improve assessment and communication for all patients in the ICU, both those who may deteriorate and equally those who may recover. PACE comprises the training programme and an assessment, which is recorded in the clinical notes. The training programme involves collaborative work between the ICU and hospital palliative care team staff to look at ways to improve communication and how the PACE questions might serve as a prompt to improve social assessment and continue communication. The record within PACE asks for assessment of five aspects of care:

1) Family Details; such as children, relationships and guardianships.
2) Social Details; such as language, culture, but also financial concerns or even the need for transport and parking for the family.
3) Patient Preferences; including any previous wishes about who they would want to inform their treatment
4) Communication and information; how much the patient and the families are aware of the situation and who is key in a family  to be involved in communication. It also involves explaining what happens in the ICU and finally any other aspects which the patient, family or staff feel is important. The record then gives space for a continuing log of any communication updates. This is so when the clinical  team change during the 24 hour period, everyone is kept up to date.
5) Any other issues; a list providing useful resources as a prompt for staff to receive additional support if needed. PACE is completed by the key worker for the patient, usually a nurse within 24 hours of admission.

In your study you have tested PACE in an ICU setting. How could PACE be implemented on a wider scale and in other settings?

We tested PACE in ICU because it is where there is a lot of uncertainty for patients and families. But similar needs for good communication and psychosocial care, and the presence of uncertainty, exist across the healthcare system. PACE helps the staff to get to know the patient and family better, and helps the family and patient feel that someone is interested in them and their wishes, as well as in the purely biomedical aspects of their condition. So we believe it could be helpful in other settings, especially in hospitals but this would need testing. In ICU there are higher levels of staffing than the rest of the hospital, so it may be more difficult to train staff to ask the questions correctly, and to listen well to families and patients’ answers and wishes. There may be a need to modify the training component of PACE or the questions it asks for it to best work in other settings.

How easy will it be to implement PACE into clinical practice and what will this involve?

The implementation of any tool is important as a tool is only as good as the implementation that supports it. We deliberately kept PACE short, so it couldn’t be a tick box exercise or a check list – we wanted the staff to think about what the assessment meant and to take the time to listen to patients and families. Our research in the implementation found that in general PACE was completed within 24 to 48 hours of admission (only about half of PACEs were completed within 24 hours and the rest within 48 hours). Most people found it easy to record the family history, the family condition and the social circumstances but more difficult to ask about prior preferences that the patient might have. This is where the training and support, which needs to be ongoing, is important.

What’s next for your research? Are their plans for a Phase III study of PACE?

We want to test PACE more widely and a Phase III study is exactly the right next step. We would like to try this in several centres – at the moment PACE has been tested in one hospital. We are about to plan an expansion of the work and seek potential partners. We want to see if there are benefits of PACE but also if there are any downsides to using it. So far, we are encouraged because it appears that PACE is not only feasible but it seems to improve communication, information, the families perception of the honesty of staff, and symptom control. The next test is to evaluate this further with comparative trials. Our development and preliminary evaluation was supported by the UK National Institutes of Health Research (NIHR), and we will need to approach them or a charity to support the next phase in the work.

Fluorescently tagged polyglutamine expansions expressed in the muscles of a laboratory strain of C .elegans (Bristol N2, left) and a wild strain (DR1350, right). Image source: Gidalevitz et al, BMC Biology, 2013,

C. elegans has already proved useful for studying the cellular toxicity caused by polyglutamine and other disease-associated proteins in the fixed genetic background of a laboratory strain, and the new research extends the utility of the model by showing that numerous natural genetic modifiers of polyglutamine disease  exist in wild worm populations. Previous work has already identified specific genes and pathways that can be manipulated to modify the phenotype caused by protein destabilizing mutations, but amelioration of disease is often achieved at some other cost to the organism. The study establishes C. elegans as a genetically tractable model for identifying modifiers of protein homeostasis among natural variants shaped by selection for the overall fitness of the organism, and could lead to new therapeutic targets.

A worm which as an adult has only about 1,000 cells overall and 301 neurons may seem an unlikely model for studying human neurodegenerative disease, but the cellular pathways governing protein homeostasis are conserved across eukaryotes, and as Matt Kaeberlein from the University of Washington Medical Center, USA, explains in a commentary accompanying the publication of the research article, C. elegans has several features that have contributed to its utility as a model organism, and key aspects of proteotoxic diseases are recapitulated in transgenic worms expressing aggregation-prone proteins.

In the polyQ disease model used by Gidalavitz and Morimoto (one which was originally developed in the Morimoto lab),  a fluorescent-tagged peptide encoding a stretch of 40 glutamines is expressed from a transgene specifically in muscle cells, allowing age-associated aggregation to be monitored in vivo, while assessing toxicity through effects on muscle function and lifespan in the same animals.  In the new study, the researchers introduced the transgene (by introgressive breeding) into three wild strains of C. elegans, finding that genetic background  affected both the age of onset and extent of aggregation, and also which subsets of muscles cells are most likely to form aggregate. They also observed that modifying effects on aggregation and measures of toxicity did not always correlate, with one wild background providing significant protection against muscle paralysis in body wall and reproductive muscle without suppressing aggregation (compared to the original laboratory strain).

The existence of modifiers that can act independently on the aggregation and toxicity phenotypes was further supported by a series of 21 recombinant inbred lines generated between the laboratory strain and the wild strain that showed the greatest enhancement of aggregation, while the existence of multiple modifiers and interactions between them was indicated by transgression – some of the inbred lines had a more extreme aggregation phenotype than either parental line. Overall the results suggest the existence of different and complex modifying pathways, which will be amenable to further dissection and characterization, and may be amenable to therapeutic manipulation.

What makes a popular pooch?
An analysis of breed statistics from the US Kennel club database, containing records of more than 50 million dogs registered over the past 80 years, finds that some traits which might be considered favourable – such as longevity, health and a good temperament – are not correlated with overall popularity, measured by ownership. Instead, breed popularity over the past century is more likely to have been driven by changing fashions and fads, than by function.
Ghirlanda et al. PLoS One

Big data from big cats: Genome sequence of the Amur tiger
The first tiger genome sequence assembly and annotation reveals a 95.6 percent similarity to the domestic cat from it which diverged 10.8 million years ago. Comparative analysis with the genomes of other big cats like the snow leopard and African lion finds possible genetic signatures for their carnivorous lifestyle and powerful muscle strength, and could prove to be a valuable resource for future conservation efforts of these threatened species.
Sung Cho et al. Nature Communications

New methods to study how cells do the locomotion
How cells interact with one another when they come in to contact can be an important part of many biological processes; for example, directing the wound healing responses of epithelia. By contrast, regulatory failure of these contact processes can lead to malignancy, manifest in the invasiveness of cancerous cells. This concept is known as ‘contact inhibition of locomotion’, but due to the infrequency and unpredictability of some contact collisions, has so far proved difficult to study. Now a new assay to restrict such collisions to a one-dimensional surface guides cells into microscale furrows on an assay plate, in order to better manipulate their motility.
Scarpa et al. Biology Open

“It is essential that plant data are made available”
The vast amount of data generated by new high-throughput methods means that far more data is generated in the course of most experiments than is often needed for their final analysis. Developments in the fields of transcriptomics, metabolomics and proteomics means that large, open-access databases are readily available in which to make this data discoverable and re-usable  for all scientists. However, understanding what data should be deposited and where can be something of a minefield. A Commentary article in the Journal of Experimental Botany aims to summarise the current state of these fields for practising plant scientists, guiding them through the available options. The authors conclude that community-driven initiatives to improve access to data are essential to foster growth in the plant sciences and related disciplines.
Leonelli et al. Journal of Experimental Botany

Apes go for grapes when given a choice
In the wild, chimpanzees live in complex groups in which social interactions may mediate foraging decisions. However, the extent to which individuals are influenced by the perceived success of their social partners may vary among different species of non-human primates. In a reward-based feeding experiment in which chimps were offered the choice of high-value items like grapes versus low-value items like celery, individuals attempted to maximise their own rewards when they had previously received low-value items, regardless of the level of reward that they had seen other chimps given. However, they would only do so if they could be certain of receiving a high-value item. When food rewards could not be improved, individuals agreed to low-value items only when their test partners were also perceived to be obtaining the same low-value items, suggesting that some form of social facilitation does operate in this species.
Hopper et al. PeerJ

Identifying the master switch in fungal spore formation
In order to reproduce successfully, filamentous fungi such as Streptomyces send out aerial spores. A protein called WhiA  plays a critical role in initiating this sporulation, with mutant fungi lacking the protein being unable to proceed to the aerial phase of spore formation. Intriguingly the protein is also found in all Gram-positive bacteria, even those that do not sporulate. Understanding the regulatory networks that switch spore formation on and off will therefore provide valuable insights into the evolution of this feature of the fungal life-cycle. Previous work on this system has been hampered by logistical problems in obtaining sufficient fungal biomass in the spore phase to be able to use genomic techniques such as CHIP-seq. However, an emerging model species, Streptomyces venezuelae is able to overcome this by sporulating entirely in liquid culture. Applying the CHIP-seq techniques to this new system has now allowed researchers to confirm WhiA as a transcription factor and characterise the genes involved in spore formation that are under its control.
Bush et al. mBio

Understanding the molecular mechanics of the C₄ system has clear implications for future agriculture and food production, yet identifying the regulatory factors involved has proved elusive. In a significant step toward this goal, Shaun Bowman and colleagues in the laboratory of James Berry at the University of Buffalo, USA, have identified a new RNA binding protein that is the first such factor to be implicated in the regulation of an individual photosynthetic gene in a C₄ plant, as published in a recent study in BMC Plant Biology.

Confocal microscopy image of the leaves of the C4 plant maize stained for RLSB (top), Rubisco (middle) and PEPcase (bottom). Image source: Bowman et al, BMC Plant Biology, 2013, 13:138

Both C₃ and C₄ plants contain mesophyll cells, which contain the apparatus needed for photosynthesis. Here, carbon-dioxide assimilating enzymes fix carbon into a usable form, with each enzyme encoded by a specific pattern of gene expression. The primary workhorse of this process in C₃ plants is an enzyme called Rubisco, yet it wastefully also fixes oxygen in the process. C₄ plants overcome this wastefulness by housing Rubisco in a different cellular compartment that is surrounded by the mesophyll – known as the bundle sheath. The bundle sheath cells play host to only the second round of carbon fixation using Rubisco; the primary round of fixation instead being carried out in the mesophyll by the enzyme PEPCase, which is more efficient than Rubisco at fixing carbon.

Although inefficient, Rubisco is nevertheless ubiquitous in plants, and essential to their growth and survival. Given this, comparing the two different photosynthetic processes and identifying what regulates the shared components of their enzymatic pathways could hold the key to understanding how they both operate.

Encoding the larger of Rubisco’s two protein subunits is a chloroplast gene known as rcbL, found in both plant types. Expression of this gene in specific cell-types like the bundle sheath is tightly controlled after transcription via specific stretches of sequences within its messenger RNA (mRNA). The proteins that bind these RNA molecules influence patterns of gene expression, and it was these proteins that Bowman and colleagues sought to find.

In a multi-layered analysis using several C₄ species and the model C₃ plant Arabidopsis, the authors identified a protein called RLSB based on its ability to bind to rcbL mRNA. In both C₃ and C₄ plants, reductions in the levels of RLSB gene expression in RLSB mutant and gene-silenced plants resulted in reduced photosynthetic function, and visibly yellowed leaves.

Confocal/DIC microscopy image of a leaf of the C3 plant Arabidopsis stained for Rubisco. Image source: Bowman et al, BMC Plant Biology, 2013, 13:138

Comparison with other plant species indicates that the RLSB protein is highly conserved across many plant species, and co-localises with Rubisco in all C₃ plant cells. The localisation of this protein specifically to the bundle sheath cells in C₄ plants now adds an extra layer of evidence pointing towards a crucial regulatory role for RLSB in the expression of Rubisco in C₄ plants as well. Taken together, this work suggests that the mechanism of RLSB gene expression observed throughout C₃ plants may have been modified over evolutionary timescales to provide a more localised, specialised, and ultimately similar function in C₄ plants.

C₄ plants currently account for around a quarter of global plant primary productivity, yet few crop species utilise this more efficient form of photosynthesis. Tellingly, it is also the competitive and adaptable grass species that are mostly characterised by this system, with C₄ plants maize and sugarcane among the crop-plant exceptions. Understanding the full scope of this photosynthetic pathway could therefore pave the way toward more highly efficient varieties of non-C₄ crops, and a more efficient answer to future food production.

To coincide with this year’s Experimental Biology conference, BioMed Central and BMC Biology organised a panel discussion to discuss the increasing frustration with the peer review process from the scientific community.

Chaired by Greg Petsko (who neatly summarised some of the problems before the discussion here) the panel brought together representatives of each role in the process: scientist, reviewer and Editor (both academic and professional).

“The thesis is that there is something seriously wrong with the scientific review process… which has become, if not outright broken, distorted to the point where it’s hindering people’s careers, and causing more problems than it is solving.”

Greg Petsko, Weill Cornell Medical College, USA

The discussion itself is summarised here, and this video brings together some opinions voiced on the evening, from Greg Petsko, Emilie Marcus, Hidde Ploegh, Josh Sanes and Laurie Goodman.

“I do think there are inefficiencies … it’s important that we look for what those inefficiencies are and identify ways to improve them… that preserve the value and quality of peer review.”

Emilie Marcus, CEO Cell Press

 

Emilie Marcus, CEO of Cell Press and Editor of Cell, gives her thoughts on the role of the Editor and the reviewer in the process, and current inefficiencies in the system.

Hidde Ploegh (whose high profile call in Nature to ‘End the wasteful tyranny of reviewer experiments’ was referenced throughout the discussion) reiterates his point that funding for science should not be being spent on time-consuming rounds of review in order to publish in high-profile journals, but to ‘get the scientific question answered’.

Josh Sanes, co-Editor-in-Chief of Neural Development, discusses the non-linear effect that journal prestige currently has on the career progression of young scientists.

“The hierarchy of journals has an effect that’s completely disproportionate to the real difference in quality of the papers that are published.”

Joshua Sanes, Harvard University

Throughout the discussion, questions and comments from the floor were forthcoming, and Laurie Goodman (Editor of GigaScience) provided an example of open peer review at it’s most beneficial (which Biome has covered in more detail here).

Goodman concludes the video with her thoughts on how opening up the process can be beneficial, but that a ‘one size fits all’ approach cannot meet the needs of differing scientific communities.

In the first of two podcasts, BMC Medicine Senior Editor Ursula d’Souza, spoke to chair of the DSM-5 taskforce, David Kupfer, on the main challenges faced by DSM-5 and its potential impact on global mental health classifications and diagnosis.

David Kupfer, professor of psychiatry, University of Pittsburgh, USA.

“We wanted this fifth edition to help clinicians more precisely diagnose mental disorders. DSM-5 does that by representing the best available science and clinical experience. This new manual is truly a guidebook that will help clinicians better serve their patients”
David Kupfer, University of Pittsburgh

David Kupfer is both professor of psychiatry and professor of neuroscience and clinical and translational science at the University of Pittsburgh, USA. Having qualified in medicine at Yale University, USA, Kupfer continued to his clinical and research training at Yale New Haven Hospital and the National Institute of Mental Health. He also served as chair of the Department of Psychiatry at the University of Pittsburgh School of Medicine, and director of research at Western Psychiatric Institute and Clinic, USA. Kupfer’s primary research interests focus on long-term treatment strategies for recurrent mood disorders, the pathogenesis of depression, and the relationship between biomarkers and depression.

Taking a view from across the pond, Eric Taylor, emeritus professor of child and adolescent psychiatry at the Institute of Psychiatry, King’s College London, UK, reviews the changes in DSM-5 with regards to ADHD, and considers whether this will affect clinical practice and what the future holds for the diagnosis of this disorder.

Eric Taylor, emeritus professor of child and adolescent psychiatry, King’s College London, UK.

“[ADHD] is not part of disruptive disorders now, it’s part of neurodevelopmental disorders, which I think is a step forward. […] The changes in DSM-5 have also made it a bit easier to diagnose ADHD in adults”
Eric Taylor, King’s College London

In addition to his position at King’s College London, Eric Taylor is an honorary consultant at the Maudsley Hospital, London, UK. Taylor has chaired the UK’s NICE (National Institute for Health and Care Excellence) guidelines development group for ADHD. He is also a trustee of the National Academy of Parenting Practitioners, non-executive director of the South London and Maudsley NHS Foundation Trust, fellow of the Academy of Medical Sciences and honorary fellow of the Royal College of Psychiatrists.

Alzheimer’s disease (AD) is the most common cause of age-related dementia, with a majority of cases having a sporadic, rather than familial, origin. Research suggests neuroinflammation of the brain is linked to the pathogenesis of the disease, however previous studies had not established whether this link was causal.

Kneusel and colleagues set out to investigate this association in a novel mouse model for sporadic AD using polyriboinosinic-polyribocytidilic acid (PolyI:C), a viral mimic that stimulates the immune system.

“It seems likely that chronic inflammation due to infection could be an early event in the development of AD.”
Irene Knuesel, University of Zurich

Based on the similarity between the changes in the immune-challenged mice and the development of AD in humans, this comprehensive study suggests that systemic infections represent a major risk factor for the development of AD. Knuesel and colleagues notably provide the first evidence that a pre-natal systemic immune challenge in mice results in chronic inflammation, increased levels of amyloid precursor protein, tau mislocalisation and cognitive impairments, all of which leave the brain vulnerable to pathological aging and AD. Moreover, a subsequent systemic immune challenge in adulthood further exacerbates the situation leading to neuropathological hallmarks representative of a precursor stage of early AD.

Guojun Bu, professor of neuroscience at the Mayo Clinic, USA and co-Editor-in-Chief of Molecular Neurodegeneration, was one of three judges for the Research Awards in this category, and commended the studies novel observation of “the close relationship between the immune system and the pathogenic process of AD.”

These findings provide compelling evidence for the causative role of systemic immune challenges in the development of AD-like neuropathology and also provides the scientific community with a unique tool, in the PolyI:C mouse model, to investigate the molecular mechanisms underlying early pathophysiological changes in sporadic AD.

“The relationship of inflammatory processes and neurodegeneration is frequently discussed but has not been seriously examined in animal models so far”, noted Research Award judge Amos Korczyn from the department of neurology at Tel Aviv University, Israel. “This study is very comprehensive, including both biochemical and anatomical changes in a systematic study of wild-type and transgenic animals. The work is outstanding and I expect it to be of high impact.”

You belong to the UK Juvenile Dermatomyositis Research Group (JDRG). What is the JDRG and what do you hope to achieve as a part of it?

The JDRG is a national group of paediatric rheumatologists and scientists who are interested in improving the understanding and clinical care  of patients with JDM, by sharing information on their patients, promoting research  and creating the largest cohort study of JDM patients in Europe.

What is Juvenile Dermatomyositis (JDM) and how rare is it?

Juvenile Dermatomyositis (JDM) is an autoimmune disease affecting approximately 3 children in every million per year. Muscles weakness and skin rash are the main symptoms of JDM and it affects every child differently with some children experiencing a mild form of the disease while others display a more severe disease progression.

What challenges exist in diagnosing and treating JDM?

As a rare disease, it is difficult to collect sufficient numbers of JDM patients to test new diagnostic criteria and plan randomised controlled trials (RCT) of new drugs. At present most treatments are based on expert opinion rather than trial data. On a more positive note, there was a recent large RCT of rituximab (anti CD20 monoclonal antibody) in adult and juvenile dermatomyositis, and international groups, such as the JDRG, are working on updating the diagnostic criteria originally published in 1975.

What did your study set out to investigate?

We wanted to find out if myeloid related peptide (MRP) would be an accurate biomarker for disease activity in JDM, and if so, what might be the mechanism that underlies this observation.

What most excited you about  your findings?

We were very pleased to see that serum MRP did correlate with other measures of disease activity in JDM. MRP is heat stable and easy measured by ELISA which makes it an ideal candidate for a biomarker in clinical practice.

What impact would a specific biomarker have on the day-to-day management of this condition?

One of the major challenges of JDM is trying to distinguish muscle weakness caused by active inflammation from muscle damage caused by corticosteroids or deconditioning. Having a specific biomarker for disease activity, would allows us to limit treatment escalation to those patients with real disease flares, and in this way, minimise iatrogenic harm from our treatments.

Your study defines a pathway by which macrophages ‘crosstalk’ and perpetuate inflammtatory myocytis. Do you think this is specific to JDM?

No, this is unlikely to be specific to JDM. Interestingly, muscle inflammation is also a feature of the muscular dystrophies and it is possible that MRP contributes to pathology in these disorders.

What’s next for your research?

We are carrying out a wider study to identify prognostic factors in JDM, by examining serological markers of inflammation (such as MRP), muscle biopsy results and autoantibody status, to identify those patients at risk of poor long term outcomes. In this way, we hope to target therapy to the correct patients, saving aggressive treatments for those patients who really need it.