Maurizio MoggioFondazione IRCCS Ca’ Granda - Università di Milano

Biobanca Telethon per Pazienti Mitocondriali:come allargare e rendere più efficace la rete

6° Convegno Nazionale sulle Malattie Mitocondriali – Roma - Maggio 2016

What is a Biobank?

human biobanks and genetic research databases (“HBGRD”), are structured resources that can be used for the purpose of genetic research and which include: (a) human biological materials and/or information generated from the analysis

of the same; and (b) extensive associated information.

Fonte: Guidelines for Human Biobanks and Genetic Research Databases (HBGRDs), OECD 2009

OECD Council (Organisation for Economic Co-operation and Development, 2009)

" a non-profit organization to be officially recognized by the health authorities of the Member States and must ensure proper handling, storage and distribution of material."

The Council of Europe recommends the health authority to consider the biobank as (2012):

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

Scientific publications on rare diseases that underline the difficulties in finding biological material from "informative" families, a process that can take up to 10 years and consequently delays research.

The necessity to avoid wasting or losing valuable samples, particularly when research activities cease (retirement, change of life).

The intensification of genomic research which raises patients' hope of better diagnoses and new therapies.

Letters from families and patients affected by a rare disease who spontaneously volunteer to participate in research on their disease by giving a blood sample or other biological material.

Reasons to establish Biobanks for Rare Diseases

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

General Privacy protection issues: “do I have the patient’s permission?” Lack of infrastructure: “I want to share data but where do I put it?” Lack of standards and interoperability

Academia Culture of protecting research results: “someone else might scoop

my publication!” Lack of incentives for sharing

Industry Competition (sharing own data) Concerns over data quality, regulatory compliance

Data Sharing: Barriers

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

Overcoming the “rare disease problem” Cohort size Powering trials Finding confirmatory cases

Reducing costsReducing duplication of effortFacilitating validation of resultsEnabling engagement with experts and the patient community

Sharing: Benefits

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

The process of TNGB harmonisation has been mainly achieved through theadoption of a unique, centrally coordinated, IT infrastructure, which has enabled (i) standardisation of all the TNGB procedures and activities; (ii) creation of an updated TNGB online catalogue, based on minimal data set and

controlled terminologies;(iii) sample access policy managed via a shared request control panel at web portal.

Telethon Network of Genetic Biobanks (TNGB), A network of non-profit Italian repositories created by Telethon in 2008

to form a virtually unique catalogue of biospecimens and associated data, which presently lists more than 750 rare genetic defects.

Telethon Network of Genetic Biobanks (TNGB)

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

Naples Human Mutation Gene Biobank

LUISA POLITANO

Neuromuscular bank of tissues and DNA

samplesELENA PEGORARO

Bank of DNA, cell lines and nerve-muscle-cardiac tissuesMAURIZIO MOGGIO

Cells, tissues and DNA from patients with

neuromuscular diseasesMARINA MORA

Cell Line and DNA Bank of Paediatric Movement

DisordersBARBARA GARAVAGLIA

Galliera Genetic BankCHIARA BALDO

Cells lines and DNA bank of Rett syndrome

and other X-linked mental

retardationALESSANDRA RENIERIGenetic Biobank from patients with Williams-

Beuren S.GIUSEPPE MERLA

Cell line and DNA Biobank from patients

affected by Genetic Diseases

MIRELLA FILOCAMO

Human genetic Bank of patients affected by Parkinson and

parkinsonisms STEFANO GOLDWURM

Founding partners Joined partners after 1-year pre-admission

period

TNGB Composition

Biobank of Genetic Samples

LUCA SANGIORGI

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

The TNGB has developed a close relationship with Family Associations

FRAME AGREEMENT in 2011 between UNIAMO and TELETHON

5 AGREEMENTS

Ring 14 International AssociationItalian Federation of Prader Willi Italian Association of Mowat Wilson (AIMW)“Nonsolo15” AssociationNational Association of Wilson’s Disease (WD)

TNGB Partners

offering a service to the patients and their families centralizing worldwide rare samples for research projects

AIMS

Promoting dissemination activities mostly in collaboration with “UNIAMO”(The Italian Federation pooling over 107 organizations of patients affected by rare diseases)

TNGB Promotion inside Family Associations

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

NETWORK BOARDCoordinator and Biobank Directors

The decision-making body

AGREED PRINCIPLES (ethical guidelines, organisation and governance policies, benefits and duties)

THE CHARTER

ADVISORY BOARD Legal, ethical and technical experts

and patient representativesPatient AssociationsThe consultive body

The funding (upper) body

TELETHON FOUNDATION

Telethon Scientific Committee for Biobanks

Research Program Manager Mary Wang

TNGB Governance

1

3

2

4

6

5

Sample requests

shared by all TNGB members

Coded data are aggregated and published

NETWORK WEBSITE

LOCAL DATABASE handles the core biobank data

(structure shared by all partners)

http://biobanknetwork.telethon.it

Harmonizing and standardizing TNGB processes has been possible thanks to this powerful tool facilitating the interactions between the pre-existing biobanks

IT Infrastructure

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

To ensure a uniform codification and classification, the diseases of the catalogue are defined by: OMIM (Online Mendelian Inheritance in Man) number, Orpha (Orphanet classification of Diseases) number, ICD (International Classification of Diseases) code.

General criteria include: guarantee that an adequate aliquot of sample be saved for patient/patients’ family

relatives, aimed at potentially retrospective analyses; sample distribution only to qualified professionals working at research or medical

institutions engaged in health-related research or health care; appropriate justification for sample use; sample transfer only if the material transfer agreement form has been signed from

Principal Investigator; project design in agreement with TNGB mission and policies.

Sample Search

General Criteria for Acceptance of Request

0

2500

50007500

1000012500

15000

1750020000

2250025000

DNAs/RNAs TISSUES CELL LLINES OTHER TYPES

Cardiovascular disordersChromosome aberrationsCraniofacial disordersDeafnessDermatologic disordersEndocrinologic disordersGenomic disordersHaematological diseasesMental retardationMental retardation X-linkedMetabolic disordersNeuromuscular disordersNeurologic disordersMovement disordersOphtalmologic disordersPrimary CardiomyopathiesRare TumorsRenal disordersRett SyndromeSkeletal dysplasiasWhite matter disorders

The Biobanks of the Network collectively preserve 75.900 biospecimens derivingfrom more than 750 different genetic defects

TNGB Samples and Pathologies

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

AustriaBelgiumDenmarkFranceGermanyGreat BritainItalyNetherlandsPolandPortugalSpainSwitzerland…

IsraelSouth Africa....

CanadaCaliforniaGeorgiaIllinois IowaKentucky MarylandMassachusettsMinnesota MissouriNew JerseyNew York Oregon Pennsylvania UtahWisconsinColombia…

Hong Kong JapanTaiwanAustralia…

Several thousands of samples have been distributed worldwide19,000 samples (2010-2014)

249 papers

acknowledging the TNGB

TNGB Distribution Service and Results

The activities related to this service can be broken intothree main categories:

1) research: in this field the Network supported 784 research projects by providing several thousands of samples

2) diagnosis: this service is an added value of the TNGB as it allows to store samples from “undiagnosed” patients for future diagnoses.In this field the TNGB fulfilled a total of 441 requests

3) family: TNGB has also supported members from 18 families at risk for a rare disease. These users, being aware that the Biobank is storing sample(s) from their affected relatives, directly contacted the concerned Biobank and requested sample(s) to be used for genetic counselling including prenatal diagnosis

TNGB Activities

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

EBB is an operating network of biological banks in Europe providing human DNA cell and tissue samples for research on rare diseases

EuroBioBank

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

• Biobank • Non-biobank Associations

Founded in 20012016: 26 memberswww.eurobiobank.orgTelethon coordination from 2011

A web-based common catalogue (www.eurobiobank.org) enables a search by type of biological material and disease

440,000 samples available at the end of 2015, 1480 sample collections

111,300 samples collected during 2006-2014 and 55,600 samples distributed during 2006-2014

On average, 13.000 samples collected (5.700 NMD samples) and 6.000 samples distributed (3.000 NMD samples) each year

30 Standard Operating Procedures developed by the network 326 publications acknowledging EuroBioBank (Sept 2014)

EuroBioBank - Results

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

EuroBioBank integration in RD-Connect and interfaces with BBMRI-ERIC

BBMRI-ERICEBB IRDiRC

projectsRD-Connect

TNGB

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

BBMRI - ERIC (European Research Infrastructure Consortium): legal entity

with headquarters (central coordination) in Graz, Austria, responsible for

coordination of the activities of National Nodes established in participating

countries.

Starting date of BBMRI-ERIC operations: 2014.

The BBMRI-ERIC Inauguration Conference taked place on September 16th,

2013.

BBMRI-ERIC

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

RD-CONNECT: a unified platform for RD research

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

FP7 Health project funded for 6 years (2012-2018) with 12M EURAn integrated platform connecting databases, registries, biobanks and clinical bioinformatics for rare disease researchOverarching objectives: Contribution to the IRDiRC objectives of delivering 200 new

therapies for rare diseases and means to diagnose most rare diseases by the year 2020

Development of an integrated, quality-assured and comprehensive platform in which complete clinical profiles are combined with -omics data and sample availability for rare disease research, in particular IRDiRC-funded research.

RD-Connect

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

WP6Ethical Specifications WP7

Communication/Dissemination

WP2Registry

databases

WP3Biobanks & Sample Catalogue

WP4OMICS

Analysis tools

WP5Systems Development

WP8Patient Engagement

WP1 Coordinations

Project run time: 2013 – 2018 Project Coordinator: Hanns Lochmüller

Biobanks for mitochondrial patients

Existing mitochondrial networks Precious samples Patients data Competences

Use SOPs guaranteeing quality Controlled distribution to researchers worldwide

Interactions Registries International existing networks

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

Opportunities Existing biological samples in TNGB biobanks

Can be searched, retrieved from the online catalogue and distributed to national and international researchers

Existing mitochondrial collections in other centers Could be transferred to existing TNGB biobank(s), through a

dedicated agreement Could be included into the TNGB catalogue, provided all quality

criteria and appropriate ELSI measures are in place, pending approval of the Telethon Biobank Committee

New collections Could establish a new agreement with TNGB

Overall return Participation in the international rare diseases patient network

EuroBioBank integration in RD-Connect and interfaces with BBMRI-ERIC

EBB IRDiRC projects

RD-Connect

TNGBBBMRI-ERIC

Italian mitochondrial

network

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

Acknowledgements

Dr. Maurizio MoggioDr.ssa Monica SciaccoDr.ssa Laura NapoliDr.ssa Raffaella ViolanoDr.ssa Patrizia CiscatoDr.ssa Patrizia Valentini

Dr.ssa Chiuhui Mary WangDr.ssa Lucia Monaco

Dr.ssa Mirella Filocamo

Dr.ssa Marina Mora

Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016

Thanksfor the

attention!Biobanca Telethon per Pazienti Mitocondriali: come allargare e rendere più efficace la rete – Maurizio Moggio – Mitocon 2016