News & updates

M12 lay version

Introduction: The BIO-NMD project is a collaboration of 12 European partners working together with the common aim of trying to identify possible biomarkers in people with neuromuscular disease. Once the potential biomarkers are identified, they will be validated in animal and cell models and in human body fluids. The biomarkers will then be validated according to EMEA rules and regulations.

The project is currently in its 12th month and this report summarises the activities of the partners since the last report in M6. It is intended only as a brief update and summary.

University of Ferrara (UNIFE)
Leader: Alessandra Ferlini

Summary: The University of Ferrara is coordinating the BIO-NMD project. In addition, they are trying to discover biomarkers by looking at DNA and RNA. The team is also involved in providing patients' samples.

Update:  During the last six months UNIFE has decided on which categories of patients should be included in the study (e.g. female carriers, DMD patients who were non-responsive to steroid treatment) and collect samples and data accordingly. 

They have finalized the design of systems which will be used to capture the sequences of genes found to be associated with DMD and COL6 myopathies using ARIADNE software. This has been decided together with Applied Biosystems (AB).

The team have analysed information provided by UNIPD about the genetic material from mice with and without the genes for COL6 myopathies treated with Ciclosporine A. They also analysed the genetic material from the muscles of three COL6 patients treated with Ciclosporine A.

Leiden University Medical Centre (LUMC)
Leader: Peter Bram ‘t Hoen

Summary: LUMC is looking for biomarkers in cells, muscle tissue and body fluids.

Update: In a search for candidate DNA biomarkers for Duchenne Muscular Dystrophy, LUMC discovered a DNA variant linked with the age at which Duchenne patients lose ambulation. This variant could indicate the mechanism by which the disease progresses. This finding was done in a limited set of 70 DNA samples collected and analyzed at LUMC and needs confirmation in larger and independent patient cohorts. To this end, other BIO-NMD partners (Newcastle, London, Ferrara and Montpellier) sent in DNA samples from their Duchenne cohorts for analysis. This has been completed and data analysis is ongoing. This example shows the obvious need for and success of collaboration between the different partners participating in BIO-NMD.

LUMC screened the serum of Duchenne patients for candidate protein biomarkers using a technique which relies on antibody detection. They found two proteins with elevated levels in DMD patients compared to healthy age-matched controls and are busy replicating these findings in new cohorts, collected by different BIO-NMD partners.

LUMC optimized different serum sample preparation steps necessary to perform mass spectrometry-based biomarker discovery, in particular focussing on detection of low abundant proteins. The initial work revealed one candidate biomarker. Validation of this potential biomarker is ongoing.

University of Newcastle upon Tyne (UNEW)
Leader: Volker Straub

Summary: The Institute for Human Genetics at Newcastle University is involved in three areas of the project: organising the collection and use of patients’ samples; social and ethical aspects of the project; and dissemination of information.

Update: Samples - The provision of a large number of human biomaterials is an essential prerequisite for biomarker discovery by the BIO-NMD project. UNEW aims to improve the availability, exchange and use of human biomaterials for biomarker research by the relevant BIO-NMD partners.

UNEW has almost completed an audit of muscle biopsy availability and a significant number of biomaterials have been identified across the three centres (UNIFE, UCL and UNEW). UNEW is in the process of arranging transfer of its muscle samples to partners. A further important aspect of the audit was looking at the feasibility of studies using serum, plasma, DNA and RNA from the same patients. A few cases where this will be possible have been identified and UNEW will discuss with partners how best to use these precious samples.

In terms of new samples collection, UNEW has successfully collected and distributed a significant number of DNA, plasma and serum samples to its partners (LUMC and UNIFE) and provided comprehensive clinical data on each patient. UNIFE and UCL have also contributed samples. UNIFE, UCL and INSERM have shared Duchenne DNA samples from their local archive.
Regular exchange of samples is anticipated over the coming months.  Consistent communication among partners will be essential in achieving this.  Clearly, it is plausible that samples from certain subgroups identified by the clinical working group will be difficult to obtain.  In this instance, reaching out to EuroBioBank and patients’ registries through the TREAT-NMD platform would be an alternative route.
Communication - In August 2010, a newsletter was produced, aimed at patients and which focussed on the ethical use of biomaterials in biobanks. This was widely distributed through TREAT-NMD and BIO-NMD’s networks as well via patient groups and it was featured in Orphanews Europe, 20 October 2010. It is hoped that this will remain relevant for several months and can be used as an introduction to BIO-NMD in lay-terms. The second issue will be produced in May 2011.

The website continues to be promoted and updated with current visits numbering more than 2600 since April 2010. The patient section of the website has now been translated into Italian, French, German and Dutch, and more languages will be sought.

The Project Ethics Board (PEB) has met via teleconference and the minutes will soon be on the website. The PEB did not identify or receive any ethical questions generated by BIO-NMD at this meeting. However, people are reminded that they can be contacted with any questions or comments via the website at:

University of Padova (UNIPD)
Leader: Paolo Bonaldo

Summary: The University of Padova is working on biomarkers in animal models.

Update: In the last 6 months, UNIPD have been studying cell self-degradation (autophagy) in mice with COL6 mutations and in Bethlem and Ullrich patients. Although autophagy is a process whereby cells break down their contents, it is important for cell survival and self-renewal. This study revealed that the dystrophic mice had reduced autophagy. Some of the key proteins involved in autophagy may be good candidates as biomarkers for the early detection of muscle defects in COL6 diseases.

In collaboration with Prof. F. Di Lisa (University of Padova), the UNIPD unit also investigated how the abnormal production of particular oxygen containing substances (reactive oxygen species - ROS) affects different muscular dystrophies, using mice as a model. A drug was used to reduce the production of ROS and this showed beneficial effects on the dystrophic phenotype and improved muscle strength in the mice. ROS represent novel biomarkers for muscular dystrophies, and it will be relevant to assess their usefulness in patients.

UNIPD have now started to investigate the regenerative potential of muscles in mice with COL6 mutations in normal conditions and in response to muscle injury, with the aim of identifying additional biomarkers which may be translated into humans.

Institute of Child Health, University College London (UCL)
Leader: Francesco Muntoni

Summary: UCL Institute of Child Health will be involved in the collection and distribution of biomaterials for the research (e.g. muscle cells, blood and urine from Duchenne muscular dystrophy patients). They have access to these samples via the MRC Centre for Neuromuscular Diseases biobank. 

They will also be involved in the search for both genetic and protein biomarkers that would indicate differences in disease progression and response to potential drugs. 

Update: During the second 6 months UCL has audited the available muscle biopsy samples from DMD and COL IV patients as well as the DNA samples from DMD patients. Approximately 200 muscle biopsies of DMD and 40 muscle biopsies of COLVI related disorders were checked. Based on the study criteria and the available material a list of patients that are going to be included into the study was created. UCL also has started the collection of plasma and serum from DMD patients that will be used for the proteomic biomarker discovery.

University of Rome Tor Vergata (UNIROMA)
Leader: Giuseppe Novelli

Summary: The university will be responsible for monitoring the results obtained across the labs involved in the BIO-NMD project. They will ensure that the methods used follow rules set out by the European Medicines Agency (EMA).
Update: UNIROMA has illustrated some of the guidelines of the EMA (European Medicine Agency) for procedures to be followed when developing biomarkers for use in the diagnostic and drug development fields. They have also highlighted the possibility for the Consortium to request "Scientific Advice" to EMA, in the future.
Now UNIROMA is also monitoring and following the drafting of new documents by EMA that could be useful for the BIO-NMD project in order to highlight them to partners.

Institut National de la Santé et de la Recherche Médicale (INSERM)
Leader: Christophe Béroud

Summary: INSERM will identify the tools used by other partners in their research. They will create new bioinformatics tools and databases to handle data generated during the project and coordinate the use of software by partners.

Update: No update was received for M12.

University of Milan (UNIMI)
Leader: Cecilia Gelfi

Summary: The University of Milan will be mostly involved with biomarker discovery by studies on patient cells, muscle tissues and body fluids as well as biomarker discovery and validation in animal models.

Update: To better understand the consequences of collagen VI mutations UNIMI have focused attention on studies of mice deficient in the protein. Analysis of three different muscles in mice with a collagen 6 mutation have indicated that different muscles are influenced differently by a lack of collagen VI.

Royal Institute of Technology Stockholm (KTH)
Leader: Mathias Uhlen

Summary: The Royal Institute of Technology (KTH) is involved in checking that biomarkers discovered during the BIO-NMD project are specific to the muscular dystrophies under study. This will involve comparing samples from patients at different stages of the diseases and under different treatment programmes with healthy controls and with patients with unrelated NMDs

Update: On the 15th of November KTH launched a new version (v7.0) of the Protein Atlas. This is a portal which has been designed to be for data storage and as a knowledge platform for use by BIO-NMD. The content includes information about how proteins are expressed by 10,100 genes. Proteins are characterised in terms of how they are expressed in normal and diseased tissue, where they are located in the cell and by size.

A study is being performed on samples provided by the consortium to test for a range of biomarker candidates suggested by BIO-NMD partners. The sample collection includes 48 samples collected from DMD patients and healthy people.

Ariadne Genomics Inc (ARIADNE)
Leader: Nikolai Daraselia

Summary: Ariadne's role within BIO-NMD is to develop a literature-derived biological knowledge base focusing on Neuromuscular Diseases (NMD).

Update: Ariadne has developed the first prototype of a knowledgebase which focuses on neuromuscular diseases for the BIO-NMD project. It uses software tools and information extraction technology to gather knowledge relevant to NMDs from the literature and link it together.

This network was then used by Ariadne's experts to construct models for various NMDs and to analyse genetic data in order to come up with a list of possible (candidate) biomarkers for the NMDs. These biomarkers can now be validated by other partners in the project to make sure that they are clinically relevant.

BIO-NMD partners will have access to this prototype knowledgebase. Partners will be able to use the software to generate new hypotheses, analyze their own experimental data and validate biomarkers. Ariadne will provide a one-day training session on the use of Ariadne Pathway Studio® and MedScan Reader® software at the next BIO-NMD meeting (Dec 1st 2010, Montpellier, France).

AppliedBiosystems (AB)
Leader: Simone Guenther

Summary: AppliedBiosystems will provide technological support for methodological development using their SOLiD Next Generation Sequencing technology. The methods will allow analysis of BIO-NMD samples.

Update: One of AB's roles is to develop methods for next generation sequencing which will be of crucial importance to the whole BIO-NMD project. For this purpose the University of Ferrara has provided AB with a list of approximately 230 candidate genes and a set of samples for sequencing experiments.

Projets et Reseaux de Recherche (P2R/ACIES)
Leader: Loïc Courtot

Summary: ACIES/P2R will act as support to the project coordinator in WP
10 - Strategic and operational management. More specifically, ACIES/P2R will accompany the project coordinator in monitoring, evaluating, consolidating and submitting the project deliverables and periodic reports as well as monitoring the project progress in terms of quality, costs, schedule and risks, in accordance with EU regulations and the grant agreement.

Update: During the last 6 months ACIES/P2R organised the M6 meeting (July 7/8 2010, London) along with the project coordinator (UNIFE). The M6 meeting was an opportunity to present the work progress to the network and brainstorm. Industry was also represented. The objectives and outcomes of the project were presented to them, and they had the opportunity to interact with the researchers. For ACIES/P2R, it was also the chance to present the financial status of the project.

The management team has also monitored the progress of the project and related reports, the follow-up of the Industry meeting and supported the BIO-NMD partners in their work on a daily basis.



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