Transcript Dias nummer 1

3.5 kb
2.1 kb
5.9 kb
glutamic acid rich domain
54 kb
6.9 kb
9.2 kb
M1-M8
S1R1-R7
50
40
2.4 kb
2.3 kb
S2R1-R7
79 kb
67 kb
30
1.4 kb
40 kb
10
ATG
20
17 kb
5’UTR
3 kb
S3R1-R7
S4R1-R7
S5R1-R7
S7R1-R7
S6R1-R7
92 kb
72
60
3.9 kb
2.3 kb
5.9 kb
S9R1-R7
S10R1-R7
4.5 kb
S12R1-R7
S11R1-R7
152 kb
92
2.3 kb
2.3 kb
S158.2 kb
8.2 kb
166 kb
187 kb
122
112
3 kb
8.2 kb
173 kb
132
S13R7 S14R1-R7
S13R1-
138 kb
82
126 kb
102
3.1 kb
S8R7
S8R1-
114 kb
5.1 kb
5.5 kb
S16R1-R7
S17R1-R7
S18R1-R7
209 kb
142
4.3 kb
S19R1-R7
4.5 kb
S21R1-R7
TAG
4.0 kb
M176 – M185
4.6 kb
M163 - M175
249 kb
245 kb
182
172
237 kb
S22R1-R7
183
S20R7
S20R1-
222 kb
152
199 kb
162
S15R1-R7
3’UTR
Serine rich + SH3 domains
untranslated exons
differentially expressed exons
exons encoding unique end domains
exons encoding super repeats
exons encoding simple repeats
DEN SVÆRE DIAGNOSE
Hvem drejer (rehabilitering) sig om
Thromsø 2007
1918
Pompe
1932
Centronucl. myopathy
1967
CMT (1a)
1886
SMA
1895
ALS
1862
Cure
Myotonic dystrophy
Medical trials
1965
Animal exp.
Emery Dreifuss
Animal models
1980
Prot. function
LG (2D)
Gene product
1885
Variation of gene
FSH
Gene-isolation
1860
Gene-localisation
Duchenne/ Becker
Epidemiology
Diagnosis:
Diagnostic criteria
Description
Progress in
diagnostics and
treatment in
Neuromuscular
Disorders
Enzym replacement terapy
Pompe disease
Cori GT. Harvey Lect. 1954;8:145-171. Engel AG. Brain. 1970;93:599-616. Hers HG. Biochem J. 1963;86:11-16.
Hirschhorn R, et al. In: The Metabolic and Molecular Bases of Inherited Disease. 2001:3389-3420.
Hudgson P, et al. Brain. 1968;91:435-462. Pompe JC. Ned Tijdschr Geneeskd. 1932;76:304-312.
Reuser AJJ, et al. Eur J Pediatr. 2002;161:S106-S111. Stoeckle H, et al. Am J Cardiol. 1961;8:675-681.
OVERVIEW
Genetherapy
Engineering mini - genes
Utrophin upregulation in DMD
Oligonucleotide-mediated gene
editing for neuromuscular disorders
Bosnic DMD Family
Holiday, Visiting a camp in the
south of France, 2000
Impairment
Activity
Participation
Does he have a good life (1994)
Health service professionals:
80% no
18% don`t know
2% yes
Does he have a good life
Average population
50% no
30% don`t know
20% yes
Does he have a good life
The patients themselves
2% no
18% don`t know
80% yes
He can use 2 fingers ...
Prevalence trends in relation to the introduction of ventilator
use in the DMD population, absolute numbers Denmark
1977-2001
60
40
25+ years
30
20-24 years
20
10
Five processes forming a
DMD-ventilator policy
Creation of two
respiratory centres
2001
1999
1997
1995
1993
1991
1989
1987
1985
1983
1981
1979
0
1977
Prevalence per 01-01
50
Ventilator becomes
a standard measure
From: Jeppesen J et al.
Neuromuscular
Disorders 2003;10: 804812
European Neuro Muscular Centre
(ENMC)
Aims:
• To usefully and efficiently contribute to the
eradication of neuromuscular diseases
• To improve efficiency in European
neuromuscular research
• To facilitate and support research
communication between European (and
international) researchers and clinicians
European Neuro Muscular Centre
(ENMC)
• First established in 1989 in Paris, France
• Under the auspices of the AFM & EAMDA
• Barataud & Emery & Poortman : the “winning
ticket”
• Independent from EAMDA since 1992
• Permanent Secretariat based in Baarn, NL
• Virtual Centre, not a facility
• Workshops in NH Hotel (Naarden, NL)
ENMC Members
•
•
•
•
Austria (OEMF)
Denmark (MSFV)
Germany (DGM)
Italy (Italian Telethon)
Associate member:
Pending :
• The Netherlands (VSN, PBF)
• Switzerland (SSRM)
• United Kingdom (MDC)
France (AFM), Spain (ASEM)
Slovenia (to be approved)
Russia
ENMC ORGANIZATION
EXECUTIVE COMMITTEE
Patient organizations (7 voting members)
Chairman : Wolfgang SAMESCH, Austria
(Jes RAHBEK Danmark )
RESEARCH COMMITTEE
11 elected members
Chair: Prof. K. Bushby, United Kingdom
(Prof.John VISSING Danmark)
Research Committee
(Jan. 2007)
•
•
•
•
•
•
•
•
•
•
•
•
Prof. Bushby, UK – CHAIR
Prof. Jaques Beckmann, Switzerland
Prof. Enrico Bertini, Italy
Prof. Reginald Bittner, Austria
Prof. Kate Bushby, United Kingdom (Chair)
Prof. Baziel van Engelen, The Netherlands
Dr. Pascale Guicheney, France
Prof. Isabel Illa, Spain
Dr. Thierry Kuntzer, Switzerland
Prof. Hanns Lochmueller, Germany
Dr. Michael Rose, UK
Dr. John Vissing, Denmark
• Honorary Members : Fardeau, Dubowitz, Nigro, Rüdel, Emery, Urtizberea,
Hughes
Topics of Workshops (1990 - 2006)
Total of 147 Workshops
• Spinal Muscular Atrophy
• Duchenne Muscular Dystrophy
• Congenital Muscular Dystrophies
11
• Charcot-Marie-Tooth disease
• Emery-Dreifuss Muscular Dystrophy
• Mitochondrial diseases
• Nemaline Myopathy
15
15
8
7
8
6
Participations in Workshops 1997-2006
300
250
200
226
238
236
196
211
233
183
180
136
150
221
100
50
0
1997
1999
2001
2003
2005
Number of ENMC Workshops 1990 - 2006
14
12
10
8
6
4
2
0
0 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06
9
19 19 19 19 19 19 19 19 19 19 20 20 20 20 20 20 20
Professional backgrounds
Workshop participants 2006
Basic sciences
27%
Pathology Genetics
9%
4%
Neurology
33%
Others
11%
Paediatrics
16%
Workshop participations
by country of origin (2006)
•
•
•
•
•
•
United Kingdom
France
Germany
Italy
Netherlands
USA
28 %
14 %
13 %
8%
8%
8%
30 countries represented overall in 17 years
Results of ENMC 1990-2006
• Collaborative Workshops
147
• Consortia
18
• Participants
2523
• Publications
209
DISSEMINATION OF KNOWLEDGE
books, workshop reports, scientific papers, website,
presentation and posters at international meetings
Beyond presentations…
…much interaction,
interactivity,
and socialization…
…leading to more
collaboration
ENMC
Initial
Policy

Collaborative workshops +++

Top priority : genetic studies

Diagnostic criteria, consortia, DNA banking

Collaborative research projects >>> gene identification

Epidemiological studies

Establishment of Expert Centers in NMD
ENMC Trial Network (I)
Aim:
To facilitate and support relevant, European
multi-centre clinical trials on neuromuscular
diseases making use of the existing ENMC
prestige, ENMC network and ENMC facilities
Launched by Prof. A. Urtizberea (2001)
Continued and structured by Prof. R. Hughes (from 2003)
ENMC Trial Network II
•
•
•
•
•
•
•
•
•
38 titles for systematical reviews (Cochrane)
35 publications of protocols
40 publications of reviews
Identification of 6 key trials
6 Initial Trial Workshops
Identification of 13 second priority trials
Assess possibilities for disease register
Trial development training courses
Identification of potential treatments through
basic scientists
Next Challenges for ENMC

Multi-centre clinical trials


Better networking with other centres




Muscular Dystrophy Association (USA)
Asian Oceanian Myology Center
Integration of Eastern European countries


Uniform outcome measurements, patients registries, funding
and more generally, developing/emerging countries
Secure funding (including through E.U.
projects)
………
HISTORY
Traditional ENMC
activities
Workshops:
•Diagnostic Criteria
2007
Traditional ENMC
Activities
ENMC
Review / Focus
Priority Diseases
•Clinical Research
Website/Dissemination
of Information
TREAT-NMD
Partnership
as
•Fundamental Research
•Trials
FUTURE
Integrated
Platform for
Communication
Pseudomised
Database
Funding Resources
Counseling
Communication
non EU Countries
Assistance
in
Formation
of new
Consortia
Previous input and
directions
New directions for the ENMC, December
2005, Prof. K. Bushby
Clinical trials and research arms of
ENMC activities combined will allow for
new possibilities to be developed.
Extension of ENMC activities beyond
core program of workshops
Previous input and
directions – cont’d
Invite participation in EC from disease
specific charities with overlapping
interests.
Closer links with patient organisations
Identify and foster key areas of promise
of advance in NMD research, with
applications for workshop funding
Promotion of areas for translational
research
RehabiliteringsCenter for
Muskelsvind
Brickless
22-25 Oktober 2008
[email protected]