Inherited Neuromuscular Diseases: Translation from Pathomechanisms to Therapies

311 Pages·2009·3.224 MB·English

by  Carmen Navarro, Susana Teijeira, Beatriz San Millán (auth.), Carmen Espinós, Vicente Felipo, Francesc Palau (eds.)

ADVANCES IN
EXPERIMENTAL
MEDICINE
AND BIOLOGY
INHERITED
Volume 652
NEUROMUSCULAR
DISEASES
TRANSLATION FROM
PATHOMECHANISMS TO THERAPIES
Edited by
Carmen Espinós
Vicente Felipo
Francesc Palau
Inherited Neuromuscular Diseases
Volume 652
ADVANCESINEXPERIMENTALMEDICINEANDBIOLOGY
EditorialBoard:
NATHANBACK,StateUniversityofNewYorkatBuffalo
IRUNR.COHEN,TheWeizmannInstituteofScience
ABELLAJTHA,N.S.KlineInstituteforPsychiatricResearch
JOHND.LAMBRIS,UniversityofPennsylvania
RODOLFOPAOLETTI,UniversityofMilan
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· ·
Carmen Espinós Vicente Felipo Francesc Palau
Editors
Inherited Neuromuscular
Diseases
Translation from Pathomechanisms
to Therapies
123
Editors
Dr.CarmenEspinós Dr.VicenteFelipo
CIBERER-BIOBANK CentrodeInvestigación
CIBERdeEnfermedadesRaras PríncipeFelipe
Lab.Neurobiología
Avda.Campanar,21
Av.AutopistadelSaler,16
46009Valencia
46012Valencia
Spain Spain
[email protected] [email protected]
Dr.FrancescPalau
InstitutodeBiomedicina,CSIC
CIBERdeEnfermedadesRaras
C/JaumeRoig,11
46010Valencia
Spain
[email protected]
ISSN0065-2598
ISBN978-90-481-2812-9 e-ISBN978-90-481-2813-6
DOI10.1007/978-90-481-2813-6
SpringerDordrechtHeidelbergLondonNewYork
LibraryofCongressControlNumber:2009936205
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Preface
This volume contains the text of the presentations delivered at the International
SymposiumonRareDiseases“InheritedNeuromuscularDiseases:Translationfrom
Pathomechanisms to Therapies”, held in Valencia, Spain, from November 16 to
18, 2008. The symposium represents a part of the continuous efforts on diffu-
sion of science to the society of the Cátedra Santiago Grisolía and the Fundación
CiudaddelasArtesylasCiencias–ComunitatValenciana.Morethan200interna-
tionalscientistsfromdifferentcountriesofEurope,theUSA,andAustraliaattended
the meeting. The venue was the Auditorium of the Science Museum Príncipe
Felipe.
Ten years ago Alan Emery wrote in the preface of Neuromuscular Disorders:
Clinical and Molecular Genetics the following comments: “It has been estimated
that more than one person in every 3,000 has a serious disabling inherited neu-
romuscular disorder. The suffering caused by these disorders is considerable, but,
untilthelastdecadeorso,virtuallynothingwasknownoftheirpathogenesis.Any
rationaleapproachtotreatmentwasthereforeoutofthequestion.However,matters
arenowchangingrapidly.Thegenesformanyofthesedisordershavebeenlocalised
and characterised and their gene products identified and studied. The detection of
preclinical disease, the identification of heterozygous carriers and prenatal diag-
nosis are all becoming possible, and, hopefully, effective treatments may no be
too far distant.” Ten years later, more genes associated with neuromuscular dis-
orders have been reported, confirming the wide genetic heterogeneity of most of
diseases of the peripheral nervous system. Thinking genetically has become more
important and more compelling. It allows the unequivocal diagnosis of neonatal,
pediatric and adult diseases whose etiology has a genetic basis, thus providing a
more accurate prediction of natural history and prognosis, and reproductive plan-
ningforthefamily,notonlyofferinggeneticcounsellingandprenataldiagnosisbut
also preimplantational genetic diagnosis. Moreover, for a number of them molec-
ularandcellpathogenesisissuggestingnewmoleculartargetsand,morerelevant,
novel therapeutic approaches are currently developing to manage and treat these
disorders,includingnewdrugsandgeneandcellulartherapies.Wethoughtthatwas
the moment to share with clinicians, biomedical researchers, colleagues, medical
specialistsintrainingandstudentswhichisthecurrentstatusoftheknowledgeand
treatmentofneuromusculardisorders.
v
vi Preface
Thus, the main aim of the Symposium was to join outstanding physicians and
scientistsfromovertheworldwhodeveloptheiractivitiesindifferentareasofthe
neuromuscular disorders, from pathogenic mechanisms to therapies. Discussion
was oriented to talk about the state-of-the-art of inherited neuromuscular diseases
as a whole, including muscular dystrophies, mitochondrial disorders, peripheral
neuropathies, spinal muscular atrophy, motoneurone disease, ataxias and spastic
paraplegias. Participants, both speakers and attendees, had the opportunity to con-
front and compare pathogenic mechanisms and molecular targets for the different
diseases, as a forum for discussion of the rational basis of the new therapeutic
approaches.
Currentdaysareexcitingforthefieldofneuromusculardiseases.Knowledgeof
the epidemiology and natural history of the diseases is improving the perception
of these disorders by the general and specialized physicians, the general popula-
tion and political authorities. In the last fifteen years molecular genetics findings
haveimproveourunderstandingofthegenesandmoleculesinvolvedinmuscleand
nerve diseases, and also have provide new tools for diagnosis. These tools allow
thecliniciansandgeneticiststooffernewwaysfordiseasepreventionsuchgenetic
counsellingbasedonspecifictestsandprenatalandpreimplantationalgeneticdiag-
noses. More recently new therapeutic approaches are coming into the field and
are of major interest for researchers. Cell therapies and gene-addressed therapies
suchexon-skippinginDuchennemusculardystrophyareanencouragingexample.
Treatment of mitochondrial disorders is not easy in many instances but in some
casesitispossibleasithappensintherecentgroupofcoenzymeQ deficiencies
10
associated with neurological syndromes for which replacement therapies may be
curativeorhaveagoodpalliativeresponse.ClinicaltrialsareongoingforCharcot-
Marie-ToothneuropathiesandFriedreichataxia,changingthepanoramawehadjust
fewyearsago.
This book provides, therefore, an update on the knowledge of certain cru-
cial aspects regarding to mechanisms and treatment of disorders of the peripheral
nervoussystem.
We would like to express our gratitude to all participants for their written
contributionsandtheveryfruitfuldiscussion.
WealsothanktheCIBERdeEnfermedadesRaras(CIBERER),theInstitutode
Biomedicina de Valencia, CSIC, the Cátedra Santiago Grisolía and the Fundación
Ciudad de las Artes y las Ciencias – Comunitat Valenciana, which provided the
personnel and the facilities to organize the Symposium. The Symposium was par-
tially funded by grants from the Ministry of Science and Innovation, Conselleria
de Educación de la Generalitat Valenciana, Fundación Premios Rey Jaime I, the
CIBERER,Genzyme,S.L.,Lilly,S.AandMerckSharp&DohmedeEspaña,S.A.,
andTREAT-NMD.
Valencia,Spain CarmenEspinós
Valencia,Spain VicenteFelipo
Valencia,Spain FrancescPalau
Contents
1 PathologyandDiagnosisofMuscularDystrophies . . . . . . . . . 1
CarmenNavarro,SusanaTeijeira,andBeatrizSanMillán
2 StandardsofCareforDuchenneMuscularDystrophy:
BriefTreat-NMDRecommendations . . . . . . . . . . . . . . . . . 13
ThomasSejersonandKateBushbyonBehalfofthe
TREAT-NMDEUNetworkofExcellence
3 GeneticsandPathogenesisofDistalMuscularDystrophies . . . . . 23
BjarneUdd
4 Phenotype Variations in Early Onset Pompe Disease:
(cid:2)
DiagnosisandTreatmentResultswithMyozymeR . . . . . . . . . 39
SamuelIgnacioPascualPascual
5 Diseases of the Human Mitochondrial Oxidative
PhosphorylationSystem . . . . . . . . . . . . . . . . . . . . . . . . 47
JulioMontoya,EsterLópez-Gallardo,
MaríaDoloresHerrero-Martín,ÍñigoMartínez-Romero,
AuroraGómez-Durán,DavidPacheu,
MagdalenaCarreras,CarmenDíez-Sánchez,
ManuelJ.López-Pérez,andEduardoRuiz-Pesini
6 Mitochondrial Diseases: A Cross-Talk
BetweenMitochondrialandNuclearGenomes. . . . . . . . . . . . 69
AntonellaSpinazzolaandMassimoZeviani
7 MitochondrialDisordersDuetoNuclearOXPHOSGeneDefects . 85
CristinaUgalde,MaríaMorán,AlbertoBlázquez,
JoaquínArenas,andMiguelA.Martín
8 CoenzymeQ DeficienciesinNeuromuscularDiseases . . . . . . . 117
10
RafaelArtuch,LeonardoSalviati,SandraJackson,
MichioHirano,andPlácidoNavas
vii
viii Contents
9 The Role of Mitochondrial Network Dynamics in the
PathogenesisofCharcot-Marie-ToothDisease . . . . . . . . . . . . 129
FrancescPalau,AnnaEstela,DavidPla-Martín,and
MaribelSánchez-Piris
10 PathogenesisandTreatmentofMitochondrialDisorders . . . . . . 139
SalvatoreDiMauroandMichioHirano
11 BiologyofPeripheralInheritedNeuropathies:Schwann
CellAxonalInteractions . . . . . . . . . . . . . . . . . . . . . . . . 171
MichaelE.Shy
12 PhenotypeandClinicalEvolutionofCharcot-Marie-Tooth
DiseaseType1ADuplication. . . . . . . . . . . . . . . . . . . . . . 183
JoséBerciano,AntonioGarcía,ElenaGallardo,CésarRamón,
andOnofreCombarros
13 Genotypes & Sensory Phenotypes in 2 New X-Linked
Neuropathies (CMTX3 and dSMAX) and Dominant
CMT/HMNOverlapSyndromes . . . . . . . . . . . . . . . . . . . 201
GarthNicholson,MarinaKennerson,MeganBrewer,
JamesGarbern,andMichaelShy
14 NaturalHistoryandTreatmentofPeripheral
InheritedNeuropathies. . . . . . . . . . . . . . . . . . . . . . . . . 207
DavidePareysonandChiaraMarchesi
15 SpinalMuscularAtrophyDuringHumanDevelopment:
WhereAretheEarlyPathogenicFindings? . . . . . . . . . . . . . 225
EduardoTizzano
16 SpinalMuscularAtrophy . . . . . . . . . . . . . . . . . . . . . . . 237
JérémieVitte,RubenAttali,NasimWarwar,IrenaGurt,and
JudithMelki
17 FriedreichAtaxia:AnUpdateonAnimalModels,Frataxin
FunctionandTherapies . . . . . . . . . . . . . . . . . . . . . . . . 247
PilarGonzález-Cabo,JoséVicenteLlorens,FrancescPalau,
andMariaDoloresMoltó
18 GeneticsandPathogenesisofInheritedAtaxiasandSpastic
Paraplegias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
CarmenEspinósandFrancescPalau
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
Contributors
J.Arenas MitochondrialDiseasesLaboratory,ResearchCenter,“12deOctubre”
UniversityHospitalandU723,CIBERdeEnfermedadesRaras(CIBERER),
InstitutodeSaludCarlosIII,Madrid,Spain
R.Artuch BiochemistryDepartment,HospitalSantJoandeDéuandCIBERde
EnfermedadesRaras(CIBERER),ISCIII,Barcelona,Spain
R.Attali DepartmentofHumanGenetics,HadassahUniversityHospital,POBox
91120,Jerusalem,Israel
J.Berciano ServiceofNeurology,ClinicalNeurophysiologyandRadiology,
UniversityHospital“MarquésdeValdecilla”,UniversityofCantabria,CIBERNED
andIFIMAV,Santander,Spain,[email protected]
A.Blázquez MitochondrialDiseasesLaboratory,ResearchCenter,“12de
Octubre”UniversityHospitalandU723,CIBERdeEnfermedadesRaras
(CIBERER),InstitutodeSaludCarlosIII,Madrid,Spain
M.Brewer UniversityofSydneyattheANZAC,ResearchInstitute,Concord
Hospital,SydneyNSW2139,Australia
K.Bushby InstituteofHumanGenetics,InternationalCentreforLife,Newcastle
uponTyne,UK,[email protected]
M.Carreras CIBERdeEnfermedadesRaras(CIBERER),ISCIII,and
DepartamentodeBioquímica,Biología,MolecularyCelular,Universidadde
Zaragoza,Zaragoza,Spain
O.Combarros ServicesofNeurology,ClinicalNeurophysiologyandRadiology,
UniversityHospital“MarquésdeValdecilla”,UniversityofCantabria,CIBERNED
andIFIMAV,Santander,Spain
S.Dimauro DepartmentofNeurology,ColumbiaUniversityMedicalCenter,New
York,10032USA
C.Espinós LaboratoryofGeneticsandMolecularMedicine,Institutode
BiomedicinadeValenciaCSICandCIBERdeEnfermedadesRaras(CIBERER),
Valencia,Spain
ix