PRESS RELEASE Proof of Concept: Gene therapy for ... · these mitochondrial diseases. And since...
Transcript of PRESS RELEASE Proof of Concept: Gene therapy for ... · these mitochondrial diseases. And since...
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ProofofConcept:Genetherapyformitochondrialdiseases
Mitochondrialdiseaseisnowthoughttobethesecondmostcommonlydiagnosed
geneticdiseaseworldwide,and,unfortunately,therearestillnoproventreatment
strategiesforthosediagnosed.ScientistsfromtheMaxPlanckInstituteforBiology
ofAgeinginColognewereinvolvedincollaborationstoapplygene-therapy
approachesinmicetosuccessfullytreatananimalmodelofmitochondrial
disease.Thismaypavethewayforfuturetherapeuticstrategiesforpatients.
Everystepwetake,everylaughwemake,everywordwesayrequiresenergy.
Mitochondriaplayacentralroleinourmetabolismandenergyproduction.
Consequently,mitochondrialdysfunctioncausesaremarkablydiversegroupof
metabolicdiseaseswithabroadrangeofsymptomsleadingtoseveredisability.“Since
the1980sitwasknownthatmutationsinthemitochondrialDNAcanleadtodisease”
explainsJamesStewart,groupleaderattheMaxPlanckInstituteforBiologyofAgeing
andcontinues“wehaveknownofthesepatientsforover30yearsandonlynowarewe
startingtodeveloptreatments”.
AremarkablefeatureofmitochondriaisthattheycontaintheirownDNA.Mutationsin
thismitochondrialDNA(mtDNA)canleadtomitochondrialdiseases,butwhethera
personwithamutationdevelopsdiseaseornotismorecomplex.ManycopiesofmtDNA
arepresentineachofourcellsand,normally,disease-causingmutationsarepresentin
onlyafractionofthem.However,ifthefractionofmutatedmtDNAmoleculesrises
aboveacertainthreshold,mitochondrialfunctioniscompromisedresultingin
mitochondrialdisease.Therefore,reducingthelevelsofmutatedmtDNAmoleculesisa
potentialtreatmentstrategy.
However,thistreatmentstrategyisnotsostraightforwardasconventionalgene-therapy
approachesdonotworkinmtDNA.ScientistsfromtheUniversityofCambridge,UKand
theUniversityofMiami,USA,developedanapproachtospecificallydegrademutated
mtDNAmoleculesincellculture.Usingamodifiedvirus,theydeliveredageneintothe
cellnucleusthatencodesaproteinthatworksasmolecularscissors.Thesemolecular
scissorsarethenproducedbythecellandtargetedtomitochondria,wherethey
specificallycutthemutatedmtDNA.
Butwouldthemethodalsoworkincomplexorganismscomposedofmanytissueslike
miceorhumansandactuallytreatmitochondrialdisease?Stewartandhiscolleaguesin
Colognecouldprovidetheanswer.Theyhadgeneratedamousemodelofmitochondrial
diseasethatcontainsaspecificdisease-causingmutationinmtDNAwhichleadsto
disordersincardiacandmusculartissue.Theytreatedtheanimalswiththevirusthat
onlyinfectedtheheartorthemuscles.Thevirusdeliveredthemolecularscissortocut
themutatedmtDNAinthetargetedtissue.Andinfact,theapproachworked!Thelevels
ofmutatedmtDNAwerereducedandthediseasesymptomswerealleviated.
“Thisisthefirstgenetherapytoactuallyremovethecauseofamitochondrialdiseasein
alivinganimal”adelightedStewarttellsus.Ofcourse,beforethetherapycanbeapplied
tohumanpatientsmoredetailedworkandsafetyassessmentsmustbedone.
Nevertheless,thescientistscouldprovethattheyfoundawaytoremovethecauseof
thesemitochondrialdiseases.Andsincethereisalinkbetweenmitochondrial
dysfunctionandotherconditionslikeAlzheimer’sdisease,Parkinson’sdisease,diabetes,
andperhapssomecancers,theapproachwillmightevenhaveahigherimpactin
fightingthosedisordersinthefuture.
Pressphoto:
Avirus-infectedcellinacellculturesurroundedbyuninfectedcells.Mitochondriaare
showningreen.Thevirusshowninorange-red(leftcell)islocatedtothemitochondria.
Scalebars:10μm(©MitochondrialBiologyUnit,UniversityofCambridge)
ApicturerequestcanbesentbyE-Mailortelephone.PleasecontactDr.Annegret
Burkert,youcanfindthecontactdetailsbelow.
Originalpublication:
PayamA.Gammage,CarloViscomi,Marie-LuneSimard,AnaS.H.Costa,EdoardoGaude,
ChristopherA.Powell,LindseyVanHaute,BeverlyJ.McCann,PedroRebelo-Guiomar,
RaffaeleCerutti,LeiZhang,EdwardJ.Rebar,MassimoZeviani,ChristianFrezza,JamesB.
StewartandMichalMinczuk:Genomeeditinginmitochondriacorrectsapathogenic
mtDNAmutationinvivo.NatureMedicine,2018DOI:10.1038/s41591-018-0165-9.
and
SandraR.Bacman,JohannaH.K.Kauppila,ClaudiaV.Pereira,NadeeNissanka,Maria
Miranda,MelinaPinto,SionL.Williams,Nils-GöranLarsson,JamesB.Stewartabd
CarlosT.Moraes:MitoTALENreducesmutantmtDNAloadandrestorestRNAAlalevelsin
amousemodelofheteroplasmicmtDNAmutation.NatureMedicine,DOI:
10.1038/s41591-018-0166-8.
contact:
Author: Dr.JamesStewart PressandPublicRelations:
MaxPlanckInstituteforBiologyofAgeing Dr.AnnegretBurkert
Phone: +49(0)22137970706 Phone:+49(0)22137970207
E-Mail: [email protected] E-Mail:[email protected]
www.age.mpg.de