• Aucun résultat trouvé

SMA: REGISTRIES, BIOMARKERS & OUTCOME MEASURES: P.191 Preliminary data for the cost-effectiveness assessment of the newborn screening for SMA in Belgium

N/A
N/A
Protected

Academic year: 2021

Partager "SMA: REGISTRIES, BIOMARKERS & OUTCOME MEASURES: P.191 Preliminary data for the cost-effectiveness assessment of the newborn screening for SMA in Belgium"

Copied!
1
0
0

Texte intégral

(1)

Abstracts/NeuromuscularDisorders30(2020)S46–S150 S103 P.191

Preliminary datafor the cost-effectiveness assessmentof the newborn screeningforSMAinBelgium

T.Dangouloff1,L.Servais2,M.Hiligsmann3

1Universityof Liege,Liege, Belgium; 2Universityof Oxford, Oxford, UK; 3MaastrichtUniversity,Maastricht,Netherlands

Neonatal screening is becoming increasingly important in the spinal muscularatrophy(SMA)landscape.Yetthereisagrowingsetofevidences that earlypre-symptomatic management ismuchmore efficientthan post-symptomatic treatment, there is however no information available on the cost-effectivenessofSMAnewbornscreening(NBS).Suchhealtheconomic analysisisneverthelessveryimportanttoconvincepolicymakerstoallocate fundsforNBS.Wewillpresentthehealth-economicdataofpre-symptomatic and post-symptomatictreatedpatients inBelgiumthatwillfurtherbeused toassessthecost-effectivenessofNBS.BetweenMarch2018andFebruary 2020, screening was conducted among71,000 newborns, among which 9 weredetectedwithSMA.Allbutoneidentifiedpatientsweretreatedbefore the onset of symptoms: 5 with nusinersen (one was mildly symptomatic at the time of treatment), 2 with Zolgensma, 1 with Risdiplam and the last one to be determined. Survival, costs and quality of life of these 9 patients(agedbetween10daysand 18months) arecurrentlyprospectively collected. In addition, data from 3 additional asymptomatic patients who were siblings of affected children arealso collected. Survival,health care resources consumption and quality of life data have also been collected on symptomatic treatedand untreated patients. For untreated patients, we collectedprospectivelythedataduringtwoyearsin81patients(53patients with SMA Type 2, 9 non-ambulant with SMA Type 3 and 19 ambulant withSMAType3).Wearealsocollecting similardataprospectivelyin30 symptomaticpatientstreatedwithnusinersenand2untreated patients,aged between4months and60 years(9patients withSMA1,14 patientswith SMA2, and9patients withSMA3).Two-thirds ofthesepatientsalready have atleast2 years offollow-up.Using thesethreesetsof data,we are currently developing a model to assess the cost-effectiveness of newborn screeningforSMA.Wewillpresentthepreliminaryresultsissuedfromthis model.

http://dx.doi.org/10.1016/j.nmd.2020.08.193

CONGENITALMUSCULARDYSTROPHIES

P.192

Gene therapy approach for LAMA2-related muscular dystrophy usinglinkerproteins

J.Reinhard1,S.Lin1,K.McKee2,P.Yurchenco2,M.Ruegg1

1Universityof Basel,Basel,Switzerland; 2Rutgers University, Piscataway, USA

LAMA2-related muscular dystrophy (LAMA2 MD or MDC1A) is the most frequent form of congenital muscular dystrophies. It is caused by mutations in LAMA2, the geneencoding laminin-α2, the long armof the heterotrimeric(α2, β1,γ 1)basementmembrane proteinlaminin-211 (Lm-211).Patientswiththeearly-onsetform lackLm-211due tobiallelic loss-of-function mutations in LAMA2. The large size of the cDNA encoding laminin-α2and theheterotrimericstructureofLm-211presentachallenge forgenereplacement orgeneeditingstrategies.Toovercomethis,wehave designed tworather smalllinkerproteinsthat qualifyforadeno-associated virus (AAV)-mediated gene delivery.This strategytakes advantage of the compensatory expression of laminin-α4, giving rise to Lm-411 (α4, β1, γ 1), present in LAMA2 MD biopsies and laminin-α2-deficient mice. Lm-411only formsalabilemusclebasement membraneand thusisunableto functionallycompensateforthelossofLm-211.Toovercomethefunctional deficit of Lm-411, one linker protein, called mini-agrin (mag), mediates bindingofLm-411tothesarcolemmalLm-211receptorα-dystroglycan.The secondlinker, calledαLNNd,consistingoftheN-terminalpartof

laminin-α1 and the laminin-binding site of nidogen-1, allows polymerization of Lm-411.Whenaddedtogether, Lm-411and thelinkers form a functional muscle basement membrane in vitro and upon transgenic expression in dyW/dyWmice,amousemodelforLAMA2MD.Consequently,themuscular dystrophy in dyW/dyW mice is largely improved, overall body weight is increasedandmediansurvivalisdrasticallyextendedfrom15weeksto81 weeks(Reinhardetal.,ScienceTransl. Med.,2017).Wewillpresentdata fromourongoing effortstoevaluate thetherapeuticpotentialofthelinker proteinsbytargetingdifferenttissuesatdifferenttimepointsandbytesting thepossibility to use AAV9-mediated deliveryof thelinkers to dyW/dyW mice.

http://dx.doi.org/10.1016/j.nmd.2020.08.194

P.193

Collagen VI-related myopathy. Clinical and genetic findings in a largeChileancohort

B.Suarez,J.Jofre,M.Martinez-Jalilie,M.Diemer,X.Ortega,T.Vial,S.Lillo, M.Haro,G.Calcagno,M.Palomino,C.Hervias,C.Castiglioni

ClinicaLasCondes,Santiago,Chile

Collagen VI related myopathy is one of the more prevalent inherited neuromuscularmyopathies.Determiningthegeneticandclinicalfeaturesin ourpopulationisrelevantto improvepatientscareand developa platform forcollaborativestudiesandfutureclinicaltrials.Wedescribethephenotype, genotypeandmuscleMRI(WBMRI)inaseries ofpatientswith Collagen VI-RelatedMyopathy(COLVI-RM).Aretrospective studyofpatientswith a geneticdiagnosis of Collagen-VI-RM, IRB-approved. Demographic data andpatients’ characteristics were obtainedfrom medicalrecords. Eighteen patients(9families)withCOL6mutationfromtwenty-onepatientssuspected ofCOLVI-RM.12/6(female/male),agerange1-54yearsand (average:25 years).AllpatientspresentanautosomaldominantCOL6-relatedcondition; 4/9 were de novo mutations. 5/9 families carrya COL6A1 mutation,3/9 families a COL6A3 and one family a COL6A2 mutation.Ageof disease onset was before the age of two in 9/18. (motor delay, frequent falls, hip dislocation), followed by neonatal onset (5/18) (hypotonia, congenital torticollis, hip dislocation). A one-year-old patient was diagnosed at pre-symptomaticstate.MostpatientspresentedtypicalCOLVI-RMskinlesions (16/18)and distalhyperlaxity.Mostshoweda slightelevationof totalCK (261-500). Muscle biopsies from 9 patients showed a dystrophic pattern in 5, nonspecific myopathic pattern in 4 patients. Seven patients had a WBMRIprevioustogeneticdiagnose;allofthemshowedthecharacteristic involvementofmusclesdescribedinCOLVI-RM.16/18 patientsdeveloped a Bethlem phenotype, maintaining ambulation. Two patients presented an Ullrichdystrophy phenotypeand ventilatoryfailure. COLVI-RMdominant conditions and Bethlemmyopathy phenotype are prevalent in our cohort. WBMRIisausefultoolthatguidesthediagnosticprocess.TheuseofNGS helpstoshortenthediagnosticodysseyandperformabetterclinical follow-upandgeneticcounselling.

http://dx.doi.org/10.1016/j.nmd.2020.08.195

P.194

Diet, motor activity & daily activity limitations in individuals with

SELENON(SEPN1)relatedmyopathy

J. Prystupa1, R. Alvarez2, C. Genetti1, E. Weller1, S. Liu1, B.Moghadaszadeh1,E.Troiano1,A.Beggs1

1BostonChildren’sHospital,Boston,USA;2CureCMD,Lakewood,USA

SELENON (SEPN1) relatedmyopathies (SELENON-RM) are a group ofrarecongenitalmyopathiescausedbymutationsin theSELENONgene. SELENON-RMpatientstypicallypresentwithaxialweakness,spinalrigidity, scoliosis,decreased stamina,lowbody mass,and respiratoryinsufficiency; however, there is a wide range of symptom severity in these patients,

Références

Documents relatifs

Archimède, L’Arénaire Si des nombres sont continûment en pro- portion à partir de l’unité, et que cer- tains de ces nombres sont multipliés entre eux, le produit sera,

Erst nach Initialisierung einer Steroidtherapie mit Prednisolon 20 mg p.o./Tag zeigte sich eine leichte Verbesse- rung des Allgemeinzustandes.. Etwa 1 Monat nach Symptombeginn

rappelons-le, sont celles choisies par Napier. Il s’ensuit donc que la constante de propor- tionnalité ici en jeu est k = 1. Dit autrement, la vitesse du point P est un temps donné

Fourth, it would be helpful, in particular for medical stu- dents and residents, if the authors could rank the relevance of the different topics within a chapter (e.g.,

Elles constituent cependant une invitation à une mise à l’essai ou à une vérification dans la pratique en vue de favoriser l’empowerment des infirmières, la recherche d’un sens

Toutefois, malgré ces pressions, il est du devoir des bibliothèques de lecture publique de mettre à disposition du public de l’information complète et non-subjective sur

➢ Le TP de mécanique de solide se fera en une seule séance de 3h, dans ce but les étudiants devront préparer à l’avance les deux manipulations (N°1 : Moments d’inertie et N°2

Design and test of a power resistors based soft-starter for a small induction generator based grid connected wind turbine.. Design of a discrete PI controller is