TREAT-NMDServing the neuromuscular community

INTRODUCTION04 An introduction from the coordinators

05 Creating partnerships to build essential resources

DEVELOPING RESEARCH RESOURCES07 TREAT-NMD Advisory Committee for Therapeutics (TACT)

08 Biobanks for neuromuscular diseases

08 Preclinical research on animal models: creating consensus and developing SOPs

08 Facilitating research networking and collaboration

SUPPORTING THERAPY DEVELOPMENT09 Patient registries

10 Outcome measures research and validation and the Registry of Outcome Measures (ROM)

11 Engaging with regulatory authorities

12 The Care and Trial Site Registry

13 Regulatory affairs database

13 Advisory support for industry

IMPLEMENTING BEST PRACTICE15 Standards of care guidelines

15 Training and education

CATALYZING NEW DEVELOPMENTS18 Catalyzing new developments

21 TREAT-NMD: the future

22 Acknowledgements

22 TREAT-NMD partners

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AN INTRODUCTION FROM THE

COORDINATORS

Recent years have seen rapid developments in the neuromuscular field and a corresponding surge in

interest from the pharmaceutical industry.Promising preclinical results raise thepotential for new therapies in the nearfuture.

Yet translational research towardstherapy development for neuromusculardiseases has faced a number of barriers.

For patients, promising research resultshave still not been translated into thetreatments they hope for, while lack ofstandardized care guidelines preventsmany from receiving optimal care.

For the biomedical industry, identifyingthe investigators and sites with therelevant expertise and accessing theappropriate patient cohorts for clinicaltrials has been a significant challenge.

For clinicians and researchers, lack ofsupport tools such as validated clinicaloutcome measures or standard operatingprocedures for research protocols hasheld back therapeutic development.

TREAT-NMD addresses all these issues,uniting the stakeholders in the communityand providing an infrastructure that isaccelerating research and therapydevelopment, increasing collaboration,improving patient care and helping tosupport ‘clinical trial readiness’ on aninternational scale.

TREAT-NMD was established as a EU-funded ‘network of excellence’ with the remit of ‘reshaping the researchenvironment’ in the neuromuscular field.The network has developed from itsEuropean roots to become a globalorganization bringing together leadingspecialists, patient groups and industryrepresentatives to ensure preparednessfor the trials and therapies of the future while promoting best practice today.

Professors Kate Bushby and Volker StraubTREAT-NMD coordinatorsNewcastle University, UK

Introduction

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“““By providing carefully designed infrastructure to support allstages of therapy development, and promoting necessarycollaborations among patients, advocacy groups, academicinstitutions, industry, and governmental agencies, internationally,TREAT-NMD is becoming the essential, go-to resource to advancenovel treatments for devastating neuromuscular diseases.”

John D. Porter, Ph.D. Program Director, Neuromuscular Disease NINDS/NIH Office of Translational Research

CREATINGPARTNERSHIPS

TO BUILD ESSENTIALRESOURCES

At the heart of TREAT-NMD is acommitment to bringing real patientbenefit through partnerships betweenclinical and scientific leaders in the field,advocacy groups and industry to developthe resources for therapy developmentand delivery.

Partnering with patientadvocacy groupsClose relationships with the majoradvocacy groups in the field have beenkey to the network’s success. The initialEuropean Union funding for the networkwas advocated for by patient groups, in particular the Association Françaisecontre les Myopathies (AFM, the FrenchMuscular Dystrophy Association), withthe support of the European Organisationfor Rare Diseases (EURORDIS). Thenetwork’s original supporters have been joined by the major advocacyorganizations across the globe, bothdisease-specific groups and those with a broader remit. To each of them TREAT-NMD can offer advice, expertiseand key resources. In return, researchersand clinicians within TREAT-NMD can benefit from the knowledge andexperience patient groups can provide.

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“As a parent organizationdedicated to the battleagainst neuromusculardiseases, AFM has beendeveloping over the years an ambitious program aimedat building knowledge andsetting up new treatments.

Overcoming bottlenecks has become a priority astherapeutic developmentprogresses. In this view,TREAT-NMD is a keynetwork that successfullyaddresses major issues.Important tools and strongexpertise are being providedto the scientific and medicalcommunity, which willundoubtedly help acceleratecutting-edge therapies forotherwise unmet medicalneeds.”

Serge Braun, PharmD, PhDScientific Director, AFM

Addressing all inheritedneuromuscular diseasesThe platform developed by TREAT-NMD,which initially focused on Duchennemuscular dystrophy (DMD) and spinalmuscular atrophy (SMA), is nowrecognized to be of benefit to all inherited neuromuscular conditions.

Strong collaborations have been builtacross the neuromuscular community by engaging numerous internationalresearchers and organizations worldwide,who are able to tap into the resourcesdeveloped by TREAT-NMD. Theseresources span the research and clinicalarenas and form a suite of tools that are essential for rapid progress towardsnew therapies.

Tools include:

• Advisory committee for therapeutics

• DNA, cell and tissue biobanks

• Consensus and SOP generation foranimal models

• Patient registries

• Network of care and trial sites

• Outcome measures for NMD

• Regulatory links

• Support for further grants

• International standards for diagnosisand care

• Focused training and education

Introduction

Case study:Congenital muscular dystrophies

Partnership with Cure CMD, a US-based patient advocacy groupfor congenital muscular dystrophies

• Cure CMD registry for all CMD subtypes (CMDIR) established,feeding into TREAT-NMD gene-specific registries

• International conference addressed issues of trial-readiness in CMD, including outcome measures, animal models, andtherapy prioritization.

• Consensus process led by Professor Thomas Sejersen(Stockholm) and Dr Ching Wang (Stanford University)involving workshops with leading CMD experts led to thedevelopment of care standards for CMDs

• Researchers with promising preclinical results on CMD targetsare encouraged to submit applications to TACT for review

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TREAT-NMD ADVISORYCOMMITTEE FOR

THERAPEUTICS (TACT)

Of the many promising research resultspresented at conferences, published in journals and hailed as the basis forpossible future treatments and cures,few progress into clinical trial. Evaluatingthe therapeutic potential of drugsseemingly ready for this step is achallenge not only for the patients who build hope on preclinical results and for the potential funders andindustry sponsors of the research, butalso for the researchers themselves.

TACT, the TREAT-NMD AdvisoryCommittee for Therapeutics, is an expertmultidisciplinary body that provides theneuromuscular community (clinicians,researchers, patient advocacy groups andindustry) with independent and objectiveguidance on advancing new therapies(whether novel or repurposed) forneuromuscular diseases.

Its goal is to position the potentialtherapy along a realistic pathway toeventual clinical trial and registration by evaluating preclinical data as well as drug development considerations that are crucial for the conduct of studiesthat generate meaningful data. In closecollaboration with the TREAT-NMDclinical trials coordination centre(Freiburg, Germany), TACT is alsodedicated to providing information onoptimal trial design and the resourcesavailable to investigators and industryfor clinical trial planning and conduct.

Core Committee Members

• Cristina Csimma PharmD MHPVice President, Drug Development, VirdantePharmaceuticals Inc, Cambridge, MA, USA.

• Didier Caizergues PharmD DESSHead of the Regulatory Affairs Departmentat Généthon, France.

• Petra Kaufmann MD MScDirector of the Office of Clinical Research,NINDS, USA.

• Rudolf Korinthenberg MDHead of the Department of Neuropediatrics& Muscular Disorders, Children’s Hospital,University Hospital Freiburg, Germany.

• John McCall PhDSenior Consultant, PharmaMacLLC, USA.

• D. Elizabeth McNeil MDMedical Officer, Food and DrugAdministration, Rockville Maryland, USA.

• Jerry Mendell MDDirector, Center for Gene Therapy,Columbus Children’s Research Institute,Professor of Pediatrics and Neurology, OhioState, University, USA.

• Kanneboyina Nagaraju PhD MVScAssociate Professor of Pediatrics, Children'sNational Medical Center, Washington DC,USA.

• Dominic Wells PhD MA VetMBProfessor in Translational Medicine,Department of Veterinary Basic Sciences,Royal Veterinary College, University ofLondon, UK.

Further details, together with thecomplete list of over 40 experts makingup the full committee, are availableonline at www.treat-nmd.eu/TACT

Developing Research Resources

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“The strength of TACT is its broad scientific anddevelopment expertisecoupled with the rigour and independence of itsreview process, performedin a truly global context. This committee can provideobjective and constructiveguidance from world expertsin the field that will bothhelp researchers focus onareas for development andensure the wider communityis better informed about thereadiness of new therapiesfor the next step.”

Cristina Csimma, TACT chair

BIOBANKS FORNEUROMUSCULAR

DISEASES

The TREAT-NMD-integrated resourceEuroBioBank is the only biobank networkdedicated to rare disease research inEurope, and its samples are distributed toresearchers across the globe. Led by thepatient network EURORDIS (Rare DiseasesEurope) with the guidance of EuroBioBankscientific director Professor HannsLochmüller (Newcastle), EuroBioBankprovides human DNA, cell and tissuesamples as a service to the globalscientific community conducting research

on rare diseases. Since its inception as a separate EU-funded project under theFifth Framework Programme (contract no.QLRI-CT-2002-02769), EuroBioBank hasbeen referenced in over 100 researchpapers, and a total of approximately400,000 samples are available toresearchers worldwide via the onlinecatalogue.

www.eurobiobank.org

PRECLINICALRESEARCH ON ANIMAL

MODELS: CREATINGCONSENSUS AND

DEVELOPING SOPS

Comparability of results between differentresearch groups is a major issue in the preclinical field. As the result ofinternational collaboration betweenanimal model specialists worldwide led by TREAT-NMD (Professor Markus Rüegg,Basel and Santhera Pharmaceuticals,Liestal) and the Washington WellstoneCenter (Professor Eric Hoffman and Dr Kanneboyina Nagaraju), a review of animal models for DMD has beenpublished, and a comprehensive set ofstandard operating procedures or SOPs for various experimental protocols onDMD models has been drafted and madeavailable online for the use of researchersacross the world. The SOPs are attracting

numerous downloads, and this approachto harmonization is now also beingapplied to models of other diseases.

www.treat-nmd.eu/animalmodels

FACILITATINGRESEARCH

NETWORKING ANDCOLLABORATION

TREAT-NMD is bringing scientists togetherin many different areas – from facilitatingexchange on high throughput screeningmethodologies to optimizing productionand safety of therapeutics. In oneexample, researchers working on differentantisense oligonucleotide chemistries in different labs (the MDEX consortium led by Professor Francesco Muntoni in London and the Leiden lab led by Dr Annemieke Aartsma-Rus) have beenable to set up a regular dialogue todiscuss progress and results in aconstructive and non-competitive way.This model for collaboration helps groups learn from one another andprogress more quickly, without damagingtheir competitive advantage.

A major milestone for TREAT-NMD wasthe network’s international conferencewith NIH in November 2009. With over350 participants including researchers,clinicians, patient groups, industry andregulatory representatives and a focus on facilitating cross-talk to address the barriers that are still hinderingneuromuscular translational research, itprovided a unique opportunity for takingstock and setting future priorities.

www.treat-nmd.eu/2009conference

Developing Research Resources

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PATIENT REGISTRIES

In collaboration with clinicians andpatient advocacy groups across theworld, TREAT-NMD has created patientregistries with future trials and therapiesin mind. Led by Dr Christophe Béroud(INSERM, Montpellier), the globalregistries for DMD and SMA arerecognized as a leading resource for trial planning and recruitment in thesediseases at an international level and arebeing used by industry for this purpose.They are also open to enquiries fromacademic researchers. Registries for arange of other conditions are alsounderway or in preparation.

For patients, the registries are a valuableway of receiving information andfeedback related to their condition andprovide an important connection to theresearch community. The registries aregoverned by a charter and by anoversight committee including patientrepresentatives.

Key benefits of the TREAT-NMDregistries:

• Single entry point for access to patientdata worldwide

• Registries contain a core set ofinformation including accurate,verified genetic diagnosis togetherwith key clinical data items, allupdated at least annually

• Powerful clinical trial feasibility tool:can filter patients by precise mutation,age, ambulation status, medicationtype and location

• Powerful recruitment tool: patientshave consented to being contactedabout trials for which they may beeligible

• Inbuilt patient data protection:patients are only contacted throughtheir national registry; their data iskept confidential

www.treat-nmd.eu/patientregistries

Supporting Therapy Development

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OUTCOME MEASURESRESEARCH AND

VALIDATION AND THE REGISTRY OF OUTCOME

MEASURES (ROM)

The correct choice of outcome measuresfor a clinical trial is critical to its abilityto generate meaningful data that enablesthe therapy being trialled to movetowards regulatory approval.

In an activity led by Professor EugenioMercuri (Rome), TREAT-NMD is involvedin research to define and validateappropriate outcome measures (OMs) for different conditions and is engaging in open dialogue with the regulatoryauthorities over measures for use inpivotal trials.

In related initiatives, promisingtechniques requiring furtherdevelopment and standardization such as quantitative MRI are beingmoved forward and standard operatingprocedures (SOPs) generated.

The online TREAT-NMD Registry ofOutcome Measures (ROM) and itsassociated tools are coordinated by Dr Michael Rose (London). These

resources are designed to give guidance,information and assistance to allprofessionals seeking details of outcomemeasures, including internationalcollaborative teams of reviewersundertaking the crucial task of choosingthe right outcome measures forneuromuscular disease trials, and toavoid duplication of this effort. Thesearchable registry contains informationabout outcome measures, including a description, details of validation,availability, contact details for providers,and references to related documentsincluding manuals and training videos.Review teams can record OMs bycategory as being considered for aspecific study or trial and benefit fromseeing the OM choices being consideredby other review teams. A manual givesadvice on how to assess and select OMs.

www.treat-nmd.eu/outcomemeasures

Supporting Therapy Development

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ENGAGING WITHREGULATORYAUTHORITIES

TREAT-NMD has proactively engagedwith the European and US regulatoryagencies, the EMA (formerly EMEA) andFDA, over key issues surrounding trials in neuromuscular disorders. The lack ofprevious trials in these conditions meansthat basic groundwork relating to drugregistration trials still needs to beworked out with the regulators, withissues ranging from which outcomemeasures might be consideredappropriate for granting of marketingapproval in particular conditions to the

challenges of personalized medicine forhighly mutation-specific therapies suchas exon skipping.

By convening broad, strategic meetingswith the regulatory authorities overthese issues TREAT-NMD has been able to develop close links with EMA that will guide future development for newtherapies. The approach has beenwelcomed as providing a unique forumfor discussion that benefits both sides.

Case study:EMA workshop on DMD

In September 2009 a broad group of 98 DMD experts assembledby TREAT-NMD – including clinicians involved in current clinicaltrials, patient/parent groups and pharmaceutical companiesworking on Duchenne therapies – met at the London offices ofEMA, the European Medicines Agency, to discuss the regulatoryissues surrounding the unprecedented level of personalizationinherent in antisense oligonucleotide (AO) therapies for geneticconditions like DMD. Input from Duchenne patient groups andexperts worldwide ensured that there was global representationat the meeting, which also included a representative of the USFood and Drug Administration (FDA).

Although more than 80% of Duchenne boys could potentiallybenefit from the “exon skipping” approach, each exon targetedrequires a unique AO, and thus treating all the differentmutations known to cause DMD requires the development oflarge numbers of AOs, each treating only a small subset of thepatient population. This represents a personalized approach totherapy that is currently without precedent for a geneticdisease, and concerns were raised from many different sectorsthat the regulatory hurdles might hinder the approval of drugsto treat the rarer mutations. The meeting with EMA thereforesought to take steps to identify a pathway that will allow thesafe and efficient progress of these drugs through the approvalprocess. The groups present were praised for bringing the fieldtogether in a constructive way.

More information: www.treat-nmd.eu/EMEA-antisense

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THE CARE AND TRIAL

SITE REGISTRY

Defined patient cohorts and experiencedtrial sites and investigators are essentialrequirements for any trial. The TREAT-NMD Care and Trial Site Registry (CTSR)is a database of information on clinicalsites established by the Clinical TrialsCoordination Centre under the leadershipof the German MD-NET and ProfessorRudolf Korinthenberg (Freiburg) tofacilitate the selection of centres withthe expertise to take part in clinicaltrials. Registered sites have completeddetailed feasibility information regarding

their experience, facilities, equipmentand personnel, equivalent to a companyor CRO’s early feasibility enquiry.Companies have already made use of theCTSR to assist in their site selection forupcoming trials.

The CTSR contains data on over 200registered sites in over 40 countriesworldwide.

www.treat-nmd.eu/CTSR

Supporting Therapy Development

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Case study:EMA workshop on SMA

In 2008 a workshop set up in collaboration with theInternational Coordinating Committee (ICC) for SMA helped setthe collaborative agenda for future trials in SMA. In order fortrials to move through the approval process without delays,consensus between trial planners and regulators on endpointsand novel methodologies is essential. Topics addressed at themeeting included outcome measures and trial design to bestassess efficacy in phase I/II studies in SMA, ensuring therelevancy of efficacy outcome measures used in pilot studies tolater studies, and facilitating progression from small phase I/IIstudies to larger studies in a way which would satisfyregulatory authorities.

The meeting established broader common ground between theregulatory authorities and those interested in running clinicaltrials in SMA, and outcomes included consensus on certaintypes of outcome measure and a definition of areas wherefurther development is required. It was acknowledged that it isimportant to educate the regulators about disease mechanismand disease phenotypes, and meetings such as this one weretherefore recognised as highly valuable to both sides.

More information: www.treat-nmd.eu/EMEA_SMA

REGULATORY AFFAIRS

DATABASE

The regulatory affairs database is asource of specific regulatory informationfor investigators involved in clinical trialplanning. It contains details of nationallegislation from Europe and the US.

European regulations and guidelines (e.g. from ICH and EMA) are alsoavailable.

www.treat-nmd.eu/regulatoryaffairs

ADVISORY SUPPORT FOR

INDUSTRY

TREAT-NMD brings together leadingspecialists in the neuromuscular field andis a natural partner for biotech andpharmaceutical companies developingnew therapeutics. The unique tools,services and expertise available withinthe network can support, simplify andaccelerate clinical studies.

Through TREAT-NMD companies can notonly receive advisory support fromleading neuromuscular experts, but alsoassistance in locating the centres with

the expertise to conduct specific trialsand support with patient recruitment.

The network offers consultancy in allaspects of neuromuscular trial planning,from complete set-up of a full scientificadvisory board for protocol developmentto advice on the selection of individualneuromuscular experts with preclinical,clinical, clinical evaluator, biostatisticalor regulatory expertise.

www.treat-nmd.eu/industry

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Case study:Industry enquiries

A number of companies have requested feasibility data from the TREAT-NMD patient registriesand care and trial sites registry. Examples of requests include:

• numbers of patients with specific mutations (amenable to particular therapies moving into trial)

• patients stratified by age range and ambulation status

• details of steroid use and cardiac involvement (DMD)

• total numbers of patients per country meeting specific inclusion criteria (up to 30 countriesworldwide)

• frequency of particular mutations in DMD

• feasibility data on trial sites including equipment and staffing, muscle biopsy experience, trialexperience

• details of site diagnostic capabilities – availability of MLPA analysis, point mutation detection,deletion/duplication analysis

This information and more is readily available through the TREAT-NMD resources and this candramatically speed up trial planning and thus lower the barriers to getting a trial established.

At the recruitment stage, eligible patients can subsequently be contacted through their nationalregistries in parallel with site-based recruitment efforts.

ImplementingBest Practice

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STANDARDS OF CARE GUIDELINES

Variations in care standards between andeven within countries not only impact onquality of life but also make comparisonof trial results from different centres achallenge.

TREAT-NMD has worked withinternational specialist groups andpatient advocacy organizations oninternational consensus documentssetting out best practice in diagnosis andpatient care and under the leadership ofProfessor Thomas Sejersen (Stockholm)has made these available in multiplelanguages in family-friendly form topatients worldwide. Standards of care for

spinal muscular atrophy and Duchennemuscular dystrophy are available throughthe TREAT-NMD website and as handyprinted brochures. The network isexpanding its collaborations onstandards of care to encompassadditional conditions and is committedto supporting their development anddissemination across the field.

SMA care standards:www.treat-nmd.eu/sma-care

DMD care standards: www.treat-nmd.eu/dmd-care

TRAINING ANDEDUCATION

Under the leadership of the EuropeanNeuromuscular Centre (ENMC), TREAT-NMD has capitalized on the expertiseavailable within the network and theavailability of best-practice standards todevelop training and educationinitiatives with the goals of raising carestandards worldwide, training the next

generation of neuromuscular specialists,providing trial-focused training anddisseminating expertise. Activitiesinclude focused workshops on carestandards in neuromuscular disorders,patient registry curator training andsupport for major conferencesworldwide.

Trial design trainingOwing to the relative lack ofneuromuscular trials until now,investigator-led trials have been achallenge because many potentialinvestigators do not have sufficientexperience in trial design. The TREAT-NMD Clinical Trials Coordination Centre in Freiburg runs workshopsintroducing future investigators to thefundamentals of effective clinical trialdesign and training them in developingstudy protocol drafts. These trainingworkshops focus on the specificrequirements of trials in neuromusculardiseases and explain the complexities of trial design in rare disorders andpowering trials for small patient cohorts.

Clinical evaluator / trialphysiotherapist trainingFor a multicentre study, it is essential that procedures and evaluations areperformed consistently. TREAT-NMDarranges this type of training for thepharmaceutical companies active in thefield, making use of the expert staffavailable through the network, includingleading trial physiotherapists Dr MichelleEagle (Newcastle), Dr Julaine Florence(Washington) and Dr Elena Mazzone(Rome).

ImplementingBest Practice

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Case study:DMD care standards generation

In January 2010 a major international consensus document setting out best practice in care for Duchenne muscular dystrophy (DMD) was published in the Lancet Neurology journal. Thedrafting of these guidelines was the result of a three-year-long project guided by the US Centersfor Disease Control and Prevention (CDC) using a rigorous review process that required 84international experts to consider more than 70 thousand different care scenarios. TREAT-NMDwas integrally involved in the creation of this document through the managing editorship ofnetwork coordinator Kate Bushby. To ensure patients had access to information as early aspossible, TREAT-NMD produced a set of “interim recommendations” over a year before thepublication of the full document, and once the full published article became available a closecollaboration between TREAT-NMD, advocacy groups and healthcare professionals resulted inthe publication of a comprehensive “family guide” that summarizes the main recommendationsin patient-friendly form. The full published Lancet document is now being used in countriesacross Europe by TREAT-NMD and the CARE-NMD project as the basis for lobbying anddiscussions with health authorities to work towards the implementation of best-practice care for all patients, while the family guide can be used by patients and families to assist them indiscussions of their care with their doctors. The recommendations are also being supported by pharmaceutical companies active in the Duchenne field, who recognise not only that astandardized baseline level of care is of value in multicentre clinical trials but also that therecommendation of full genetic diagnosis for all patients is of great importance.

More information:www.treat-nmd.eu/dmd-care

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Case study:SMA care standards generation

A recognition that recent progress in the understanding of the molecular pathogenesis of SMAand improvements in medical technology have not been matched by similar developments in thecare of SMA patients led to a consensus publication in the Journal of Child Neurology in 2007. 12 core members of the International Standard of Care Committee (SCC) for SMA worked withover 60 SMA experts using a Delphi process and virtual and in-person meetings to achieveconsensus on 5 care areas: diagnostic/new interventions, pulmonary, gastrointestinal/nutrition,orthopaedics/ rehabilitation, and palliative care. Consensus was achieved in several areasrelating to common medical problems in SMA, the diagnostic strategies, recommendations forassessment and monitoring, and for therapeutic interventions in each care area. The publishedconsensus statement addressed the 5 care areas according to the patient’s functional level.

TREAT-NMD experts were not only involved in the drafting of the academic article but alsoworked to produce a comprehensive précis aimed at families and general practitioners. This hasnow been made available in multiple languages in booklet and online form, and feedback hasindicated that it is seen as a tremendously valuable resource that allows patients and doctors to work together to achieve optimal care.

More information:www.treat-nmd.eu/sma-care

CATALYZING NEWDEVELOPMENTS

In uniting such a wide range ofneuromuscular specialists and other keystakeholders, TREAT-NMD has become a significant catalyst for new researchproposals and spin-off projects, all of which can take advantage of thetranslational research platformestablished by the network. Numerousfunding applications have already beensuccessful on national, European andinternational levels and others areconstantly in the pipeline. The followingthree examples of EU funded projectsutilizing the TREAT-NMD infrastructureaddress advanced diagnostics, biomarkerdevelopment and advancing care in NMD.

NMD-chipThe NMD-chip project (contract no.223026), led by Professor Nicolas Lévy(Marseille), was funded by the EuropeanUnion’s Seventh Framework Programmeunder a call for “high throughputmolecular diagnostics.

The aim of NMD-chip is to design, develop and validate new sensitive high-throughput DNA arrays to efficientlydiagnose patients affected by NMDs,specifically Duchenne / Becker musculardystrophies (DMD/BMD), limb girdlemuscular dystrophies (LGMD), congenitalmuscular dystrophies (CMD), andhereditary motor-sensory neuropathies orCharcot-Marie-Tooth neuropathies (CMT).

The new sensitive and reliable toolsoriginating from this project will allow theassessment of all known genes implicatedin a group of diseases at one time, and theefficient analysis of chip data throughoptimized read-out bioinformatic toolswill provide results within 72 hours to oneweek and thus be cheaper than any “geneby gene” approach. It is anticipated thatdeveloping these NMD-chips could allowthe cost of molecular diagnostics to bedecreased by a factor of 10.

www.nmd-chip.eu

BIO-NMDBIO-NMD (contract no. 241665), led byProfessor Alessandra Ferlini (Ferrara), is aresearch project on biomarker researchand discovery that was funded by theEuropean Union’s Seventh FrameworkProgramme in January 2010. Biomarkersare measurable bio-parameters that canbe used to monitor disease progression,prognosis and drug response, thusoptimizing the choice of appropriate andoften personalized therapies. Early-stageclinical trials are typically so short thatthey provide limited opportunity toevaluate whether there is a meaningfulclinical improvement. The identificationof surrogate endpoints to help detect theactivity of a new therapy in the earlystages of development is essential torapid progress on the development path.BIO-NMD aims to discover and validatenew genomic and proteomic biomarkers,which will be validated both in animalmodels and in human samples beforeentering into a qualification process at the EMA.

www.bio-nmd.eu

Catalyzing New Developments

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CARE-NMDCARE-NMD, led by Dr Janbernd Kirschner(Freiburg), is a project funded by the EU’s Executive Agency for Health andConsumers to implement care standardsfor DMD in 19 European countries.Although expert centres for the care ofpatients with neuromuscular diseases doexist in most European countries, manypatients still do not receive treatment inline with current guidelines. The CARE-NMD project is establishing an inclusivereference network of care centresspecializing in the treatment of DMD toanalyze current treatment practices forpatients with DMD, identify inequalitiesbetween and within participatingEuropean countries, and host informationand training workshops to ensuredissemination and implementation oftreatment recommendations at nationaland European level. Barriers toimplementation will be identified andcollaborative solutions sought in order to help stakeholders and decision-makersin the area of healthcare to take furtheraction to improve the care of patientswith DMD and other neuromusculardisorders.

www.care-nmd.eu

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Catalyzing New Developments

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TREAT-NMD: THE FUTURE

The platform TREAT-NMD has establishedfor accelerating translational researchand catalyzing new developments acrossthe neuromuscular field is one that hasalready proved its value and that itscoordinators are committed to sustainingin the long term. The future will see thenetwork further develop this essentialinfrastructure, playing an increasing rolein areas such as long-term surveillance of therapies coming into the clinic,continued regulatory and lobbyingactivities to support availability of drugswith proven efficacy, updating andimplementation of care standards acrossthe neuromuscular spectrum,

benchmarking of service delivery against care standards, supporting ideageneration from the leaders in the field,and providing training and education tosupport the development of new careand trial sites with the expertise to treatneuromuscular patients.

All of this will ensure that theneuromuscular community can moveforward together to develop thetreatments that its patients and itspractitioners have been awaiting for so long.s

“Solutions for patientsaffected by severe and rarediseases can only emerge ifall the actors work together.It is not an option but aprerequisite. This is exactlywhat TREAT-NMD does: itcreates the opportunities tomake everyone involvedmove forward together.”

Dr Ségolène Aymé Director of Orphanet

ACKNOWLEDGEMENTS

TREAT-NMD PARTNERS

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From 2007 to 2011 inclusive, TREAT-NMD is a “network of excellence” supportedthrough Priority 1 (Life Sciences, Genomics and Biotechnology for Health) of the European Union’s Sixth Framework Programme under contract number LSHM-CT-2006-036825.

Image creditsWe'd like to thank everyone who allowed us to use their photos in this brochure, in particular the following individuals:

Front cover and p21: Vitaliy and Yuliya Matyushenko (www.csma.org.ua)

p5: Peter Streng (www.enmc.org) and Boris Šuštaršič (www.eamda.org, www.drustvo-distrofikov.si)

p10: Lisa and Kayla Vittek (www.myotonic.org; www.cureforkayla.com) and the staff and patients of the Newcastle Muscle Centre.

The following partners receive funding from the European Union through the TREAT-NMD network. Close external partnerships have also been developed withnumerous other individuals and organizations across the world, and the network now has members in over 40 countries.

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TREAT-NMD Coordination OfficeInstitute of Human GeneticsNewcastle University International Centre for Life Newcastle upon Tyne NE1 3BZUnited Kingdom

T: +44 (0)191 241 8605F: +44 (0)191 241 8770E: info@treat-nmd.eu

www.treat-nmd.eu