BRITTLEBONEDISORDERSCONSORTIUM Issue11

The Brittle Bone Disorders Consortium (BBDC) is a group of physicians, researchers, and educators dedicated to learning more about Osteogenesis Imperfecta (OI).We aim to develop new treatments and to improve the overall care of patients with OI by connecting patients with support groups, expert doctors, and clinical research opportunities.

Summer

2016 Newsletter

BBDCPARTICIPATINGCENTERS

WelcometotheBrittleBoneDisordersConsortium’s(BBDC)1stnewsletter.Itismyhopethatthisnewsletterwillkeepyouupdatedontheresearchthattheconsortiumisplanningforthecomingyears.TheBBDCisaconsortiumwithintheRareDiseaseNetworkestablishedbytheOfficeofRareDiseasesResearch,NCATS.WeareagroupofresearchersacrosstheUnitedStatesandCanadainterestedinlearningmoreaboutOsteogenesisImperfecta(OI).TheBBDCcurrentlyhas9participatingclinicalsitesand1datamanagementsite.WearealsoproudthattheOsteogenesisImperfectaFoundationisaparticipatingadvocacysitewithleadershipintrainingandeducation.OurpartnershipwiththeOsteogenesisImperfectaFoundationandallofthefamilieswithOIisacriticalcomponentofourmission.ThroughthesupportoftheOIFoundationsupportedLinkedClinicalResearchCenters(LCRC)andyourparticipation,wewereabletogatherimportantinformationaboutindividualslivingwithOIandformthefoundationonwhichtheBBDCwasbuilt.WhiletheLCRCnolongerexists,withitsmissionnowsupersededbytheBBDC,wearenow

positionedtoanswermanyimportantquestionsaboutthenaturalhistoryofOIandimprovedapproachestotreatOI.Infuturenewsletters,wewillupdateyouonspecificprojectsandinformyouabouthowtobestparticipate.

Nowalittleaboutme!Iamaphysicianandscientistwhohasstudiedgeneticsofbonediseasesforover25years.IhavebeenproudtohavecaredformanyofyouoryourfamilymembersaspartoftheSkeletalDysplasiaClinicatTexasChildren’sHospitalandBaylorCollegeofMedicine.OurcurrentresearchisfocusedonidentifyingnewgeneticcausesofOI,developingbetterteststodistinguishOItypeandpotentialresponsetotreatment,andcommonmechanismsthatcausebrittleboneastargetsfornewtreatments.Forexample,wehaveplanstotestadrugthatmaybeusefulinthetreatmentofsevereformsofOI.Ultimately,wehopethatourresearchwillallowphysicianstobettercareforindividualslivingwithOI.

Ourresearchisonlymeaningfulifwearepartnerstogether.Pleasestayincontactwithus,stayinformed,andletusknowwhatisimportanttoyouandyourfamilies.Yourneedsandideaswilltodriveourefforts.Ourteamlooksforwardtoseeingyouatoneofourparticipatingclinicalsites.

Brendan Lee, M.D., Ph.D.Chairman, Department of Molecular and Human Genetics

Clinical Sites Baylor College of Medicine Principal Investigator: V. Reid Sutton, M.D. Children’s National Medical Center Principal Investigator: Laura Tosi, M.D. Hospital for Special Surgery Principal Investigator: Cathleen Raggio M.D. Kennedy Krieger Institute / Hugo W. Moser Research Institute Principal Investigator: Emily Germain-Lee, M.D. Shriners Hospital for Children, Chicago / Marquette University Principal Investigator: Peter Smith, M.D. �Co-PI: Gerald Harris, PhD, PEShriners Hospital for Children, Montreal Principal Investigator: Frank Rauch, M.D. Oregon Health and Science University Principal Investigator: Eric Orwoll, M.D. University of California Los Angeles Principal Investigator: Deborah Krakow, M.D. University of Nebraska Medical Center with Children’s Hospital & Medical Center Principal Investigator: Eric Rush, M.D. Patient Advocacy Partner Osteogenesis Imperfecta Foundation: Principal Investigator: Tracy Hart, C.E.O. Cores University of South Florida Principal Investigator: Jeff Krischer Ph.D. University of Washington Principal Investigator: David Eyre Ph.D.

The Brittle Bone Disorders Consortium (U54 AR 068069) is part of the Rare Disease Clinical Research Network (RDCRN), an initiative of the Office of Rare Disease Research (ORDR), NCATS, and is funded through collaboration between NCATS, and the National Institute of Dental and Craniofacial Research (NIDCR), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

Dr.BrendanLee

Welcome Message From Consortium PI, Brendan Lee, M.D.

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TheLongitudinalStudyofOIopenedforenrollmentAugust2015.Our1stparticipantwouldliketoshareafewwords.

Q&A

Q:Tellusabitaboutyourself.A:MynameisAndersson,Iam15andin9thgradeatXavierAcademy.Ienjoymaththemost.ButwhenI'mnotatschoolIliketoplayvideogamesandIwritealot.I'mworkingonasequeltoabookIwroteafewyearsago.Q:Whatdoyouaspiretobeinthefuture?A:I'dliketobeanauthororsomethingtodowithanimals.Q:Youwerethe1stparticipantintheLinkedClinicalResearchCentersstudyandthe1stparticipantinTheBrittleBoneDisordersConsortiumLongitudinalStudy,Whydidyouparticipateinthestudiesandhowwasthe

experience?A:Myparentsencouragedmetojointhestudies.TheytoldmeitwouldhelpdoctorslearnmoreaboutOsteogenesisImperfecta,sotheycouldhelpothers.Theexperiencehasbeeneasyandpainless-itjusttooksometime.Butitiswellplanned.Q:Whatdoesresearchmeantoyou?A:Themoreyouknow,thebetter.Knowledgeispower.Q:Wheredoyouwanttheresearchtogo?A:OfcourseI'dloveacureforOI!Q:Whatdoyouexpecttoseefromthenewconsortium?A:SincetherearemorecitiesinvolvedtherewillbemanymorepeoplewithOIinthestudy.Andwithmorepeople,thedoctorswillhavemoreinformationtostudy.

Andersson’sloveofanimalsinspiredthestoryofMissy,ahomelesslionadoptedbyafamilyinIllinois.

TheOIF–AValuableBrittleBoneDisordersPartner

AstheBrittleBoneDisordersConsortiumbecomesmoreandmoreactivetheparticipationoftheOsteogenesisImperfectaFoundationbecomesmoreimportant.Asyoualreadyknow,oneimpressivefeatureoftheRareDiseasesClinicalResearchnetworkisthedirectinvolvementofsupportingpatientadvocacygroupsinnetworkoperations,activitiesandstrategies.Eachconsortiuminthenetworkincludesrelevantpatientadvocacygroupsintheconsortiummembershipandactivities.TheOIFoundationistheleadingpatientadvocacyorganizationservingpeoplewithOIandmedicalprofessionals.AsastrongBBDCpartnertheOIFoundationhastakentheleadroleofpreparingandprovidingeducationalmaterialsfor

medicalprofessionalsthatmayormaynotseealargenumberofpeoplewithOI.It’scriticalthatmedicalprofessionalshavetheresourcestheyneedwhentreatingapersonwithararedisorderandtheOIFoundationisprovidingthatlinkbetweenphysicianandthepersonwithOI.

FormoreinformationabouttheFoundationpleasevisitwww.oif.org.

Advocacy Partner byTracyHart,CEOOsteogenesisImperfectaFoundation

Drs.DiMeglio,Tosi,andNagamaniattheInterdisciplinarySymposiumonOsteoporosis(ISO)2016MeetingsponsoredbytheNationalOsteoporosisFoundation

A message from the BBD Consortium’s 1st Participant byAndersson

Anderssonistheauthorof“Missy”

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UPCOMINGEVENTS

2016 OIF National Conference Orlando, FL | July 22-24, 2016 Morethan600membersoftheOIcommunitywillcometogetherforthreedaysofspecializedsessionsonmanagingOI,freemedicalconsultationsandfunsocialeventsforattendeesofallages!TheentireconferencewilltakeplaceattheWaltDisneyWorldSwan&DolphinResort.

The American Society of Bone and Mineral Research Annual Meeting and Exhibit Atlanta, GA | September 16-19, 2016AspartoftheAncillaryProgram,theOIFoundationissponsoringtheRareBoneDiseaseWorkingGroupmeetingatthe2016ASBMRAnnualMeeting.TheOIFwillalsohaveaboothintheexhibithall.Moreinformationwillbereleasedasitbecomesavailable.

FUNFACTS

3 billion Theaveragehumanheartbeatsmorethanthreebilliontimesinaveragelifespan.–NationalGeographic

8% Yourbloodmakesupabout8%ofyourbodyweight.–NationalGeographic

300 Ababy’sskeletonconsistsofasmanyas300bones.Overtime,manyofthosebonesfusetogether.–Pbs.org

Myinitialinterestinosteogenesisimperfecta(OI)wasspurredbymycolleagueandmentor,Dr.BrendanLee.HisvisionwastoadvancecareforchildrenwithOIandotherskeletaldysplasiasbyestablishingamultidisciplinaryclinicatourinstitution.HeaskedmeandourcolleagueCarlosBacinotojoinwithhimasattendingphysiciansfortheclinic.Dr.FrancisGlorieuxhadjustpublishedhisresultsofpamidronatetherapyforchildrenwithOIandwerealizedtheneedtoensurethatourpatientshadavailabletothemtheseemergingtherapies.

IthastrulybeenamazingtoseethetransformationinpatientcareandresearchinOIoverthepast15years.InowhaveteenagepatientswithOItypeIVwhohavereceivedtreatmentfrombirthandarenowlivingtheirlivesfully;Ihaveonegirlwhotakescontactkaratelessonsandaboywhoplayscontactfootball(certainlynotatmyrecommendationbuttheyarehavingfunanditisamazingtosee!).Additionally,manychildrenwithOItypesIII&IVareabletowalkindependentlyathomeorschoolthroughmedicalandsurgicaladvancesthataretrulyimprovingtheirqualityoflife.

Aboutsevenyearsago,IwasfortunatetobeofferedtheopportunitytoparticipateinfurtheradvancingcareandtreatmentsforOI,incollaborationwiththeOIFoundation(OIF)andDr.PeterByers.WedevelopedalongitudinalstudyofOI(theLinkedClinicalResearchCentersmulti-sitestudyofOI)thatultimatelyenrolledover550peoplewithallformsofOI.Throughresearchonhowthingschangedyear-to-yearforpeoplewithOI,wewereabletoimproveourunderstandingofbrittlebonediseaseandthishasresultedinmultiplepublicationsofnewdiscoveriesandafullerunderstandingofthechallengespeoplewithOIface.BaseduponthesuccessoftheOIF-fundedlongitudinalstudy,wewereawardedaprestigiousgrantfromtheNationalInstitutesofHealthtoestablishaBrittleBoneDiseasesRareDiseaseClinicalResearchConsortium(BBD-RDCRC).Thismulti-sitestudywillcontinueonthelongitudinalstudy,specificallyfocusingonthefollowingissues:

• Scoliosis

• Dental&craniofacialhealth

• Pregnancy

• Qualityoflife• Vertebralcompressionfracturesin

typeIOI

• Developingnewbiologicalmarkersfordiagnosisandthemonitoringofnewtreatments

• ResearchonnewmedicationstotreatOI

ItisreallyincredibletoreflectuponhowfarwehavecomeinthepastdecadeandIknowthatthisisjustthebeginningofatransformationtonewtherapiesforOI.ItisincredibletohavetheopportunitytobepartofthisrevolutionandIamincrediblygratefulforallthatmypatientsandtheirparentshavetaughtmeaboutOI.WewouldnotbewherewearetodaywithoutyourparticipationaswellasthecommitmentoftheOIFandthecollaborationofallmycolleagues.Thankyouforguidingmeonthisexcitingjourney.

V. Reid Sutton, MD Professor Department of Molecular & Human Genetics

Meet the Doctors V.ReidSutton,M.D.

Dr.SuttonattheKlebergGeneticsClinicatTexasChildren’sHospital

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Current:

NaturalHistoryStudy(BBD7701)

Thepurposeofthisnaturalhistorystudyistoperformalong-termfollow-upofalargegroupofpeoplewithosteogenesisimperfecta(OI).Wewillcollectinformationincluding:

§ medicalhistory§ numberofbrokenbones§ surgeriesdone§ medicationstaken§ abilitytowalk§ pain§ lungfunctionandbreathing§ hearing§ bonemineraldensity

TheoverallgoalistoimprovethehealthandqualityoflifeofpeoplewithOI.Wewillaskyoucomeinforyearlystudyvisitsforatleast5years.

MoreInformation

ContactRegistry

TheRareDiseasesClinicalResearchNetwork(RDCRN)BrittleBoneDisordersConsortium(BBD)ContactRegistryisawayforpatientswithbrittlebonedisordersandtheirfamilymemberstolearnaboutBBDresearchstudiestheymaybeabletojoin.Contributetoknowledgeaboutrarediseasesbyansweringquestionsaboutyourself,yourhealth,andyourqualityoflife.

MoreInformation

BiomarkerStudy

Thepurposeofthislaboratorystudyistodevelopanon-invasivetesttodetermineOIsubtype.

WewillcollecturinesamplesandlookatvariousOIbiomarkersinurine.

MoreInformation

Upcoming:

DentalCraniofacialFeaturesofOI(BBD7704)

ThepurposeofthisstudyistofindoutmoreaboutthefacialanddentalstructuresofindividualswithOI.YoumustbeenrolledintheLongitudinalstudytobeeligibleforthisstudy.WewillperformaconebeamCTofyourjawandcorrelatethephysicalfindingswithyourgeneticfindings.

PregnancySurvey(BBD7705)

ThepurposeofthisstudyistolearnmoreaboutthecourseofpregnancyandbirthingoutcomesinwomenwithOI.AllwomenwithOIareeligibletotakethisonlinesurvey.WewillusethisdatatocreateamoreextensiveclinicalstudytodetermineifbonedensitychangesduringandafterpregnancyinwomenwithOI.

PROMISstudytool(BBD7702)

ThePROMIStoolisaself-reportingon-linesurveyallowingindividualswithOItoreporttheirqualityoflife.Weplantocomparetheself-reportingresultswiththeclinicaldatacollectedintheLongitudinalstudytovalidatethePROMIStool.

DrugTherapyTrial(BBD7706)

ThisclinicaltrialwillhelpusdetermineifanewdrugishelpfulinthetreatmentofOI.Thefirstphaseofthistrialwillfocusondrugsafetyandtolerability.WewillberecruitingandenrollingadultswithsevereOI.

Youwillcometoaparticipatingclinicalcenterforaninfusion(s)ofFresolimumab.Youwillbeaskedtoprovidebloodsamplestodeterminethesafetyprofileofthedrugoverthecourseof6-12months.Wewilllookatyourbonedensityandqualityoflifetodetermineifthesefeatureschangewhileyouareonthestudymedication.

HowtoParticipate:

Usethefollowinglinks:

ParticipatingClinicalCenters

GetInvolved

ClinicalTrials.gov

OsteogenesisImperfectaFoundation

Publications:

PMID:26426884PMCID:PMC4818203GenetMed.2015Oct1.doi:10.1038/gim.2015.131.Cesareandeliveryisnotassociatedwithdecreasedat-birthfractureratesinosteogenesisimperfecta.

BellurS1,JainM1,CuthbertsonD2,KrakowD3,4,5,ShapiroJR6,SteinerRD7,8,9,SmithPA10,BoberMB11,HartT12,KrischerJ2,MullinsM1,ByersPH13,14,PepinM13,14,DurigovaM15,GlorieuxFH15,RauchF15,SuttonVR1,16,LeeB1,16;MembersoftheBBDConsortium,NagamaniSC1,16.DescriptionOsteogenesisimperfecta(OI)isaconnectivetissuedisorderthatpredisposestorecurrentfracturesandbonedeformities.SevereformsofOIarecharacterizedbyinuterofracturesandthemodeofdeliverythatwouldbesafestforthefetusinsuchsituationsisnotknown.Inastudyinvolving540patientswithOI,researchersoftheBrittleBoneDisordersConsortiumfoundthatcesareandeliverywasnotassociatedwithadecreaseintheat-birthfractureratesinOI.Thisstudyprovidedevidence-basedanswerstoaquestionrelevantfortheclinicalcareofindividualslivingwithOI.

Clinical Research Studies