Nordic Alliance for Sequencingand Personalized Medicine

Dag Undlien

Oslo University Hospital and University of Oslo

Ambition for the alliance

To facilitate the implementation of personalized medicinein a sustainable way in the Nordic countries. and to bring the Nordic countries to the international forefront in this field promising to radically improve healthcare

Establish a network of NGS expertise in the Nordics to support specific areas of common interest, including basic research and clinical implementation of precision medicine programs

Received start-up funding from Nordforsk for 2017

Goals

1. Identify key partners in all Nordic countries including both major research infrastructures in genomics as well as leading clinical environments responsible for the implementation of personalized medicine

2. Arrange meeting(s) with the identified stakeholders with the aim to:

a. Share competencies and protocols and develop common standards

b. Secure all Nordic countries access to relevant technologies

c. Work to define common solutions to common challenges

d. Develop a shared framework for the implementation of personalized medicine

e. Seek additional joint funding and identify collaborative arenas in data sharing, IT solution, technology transfer programs etc.

The great promise of genomic, personalized medicine

Examples from rare diseases

0 3 4 6 13 Age (yrs)

Normal earlymilestones

Sterotypic behaviourAggressive outbursts

global developmentaldelay

Walk, jump, eat independently, uttered 2-3 words sentences

Loosing expressiveverbal language

Regression in all domains

Profound dementia No expressive language

Spasticity, ataxia and apraxiaWheel chair bound

Hypothermia and coldintolerance

Axial_T2_BS_2010Axial_T2_BS_2012Axial_T2_VNTR_2010

Axial_T2_VNTR_2012Axial_T2_BS.1

E

Axial_T2_AboveVNTRSaggital_T1_CC_

Thin corpuscallosum

Broad folia of cerebellum

11 years

White mattersignal changes

11 years 13 years

MRI abnormalitiesExome sequenced (trio)as part of research project

D. Misceo, E. Frengen, P. Strømme et al. unpublished

Girl with gradually developing intellectual deficit and cold

intolerance

Homozygote mutation in SLCO1C1 – a brain transporter of thyroid hormones

• The finding points at a treatment option - TRIAC a T3 analog (off label)– Used to lower TSH in patients with thyroid cancer or with TH resistance due to

TH receptor mutations

• After 6 weeks on Triac, the parents report that further disease progressionhas halted and that several clinical parameters have improved– More interested and awake– May laugh at things she sees on TV. – Has uttered some words– Body temperature is now steady > 35. Hands and feet are not so cold– Walks more steps and needs less pausing when she walks– The need for bladder catheterization is significantly reduced– Less muscle spasms and less need for analgesics– Eating is better– Myoclonic jerking is reduced

D. Misceo, E. Frengen, P. Strømme et al. unpublished

Three year old boy with suspectedcancer

• Previously healthy

• Admitted to OUH in winter 2013 with anemia and low plateletcounts

• Spring 2013, signs of primaryimmunodeficiency (PID)

• Single gene tests for suspectedforms of PID were negative

• Increasing severity of PID and bone marrow transplant wasprepared despite lack ofcausative diagnosis

• Included in research project and wasexome sequenced

• Mutations in Lig 4, a DNA repairgene, identified

• Prone to severe DNA damage ifexposed to radiation

• Based upon genetic diagnosisalternative preconditioning regimenfor bone marrow transplantationcould be employed

• Now completely healthy

• Traditional bone marrow transplant procedures would likely have killedthe patient

A Stray-Pedersen, HS Sorte et alJACI, 2016 Jul 16. pii: S0091-6749(16)30624-8.

Bridging the gap – the challenges with clinical implementation – common themes

R & D

Healthcare

healthcareR&D

The challenge with imprecise data in precision medicine

In the colloquial sense, “precision” also implies a high degree of certainty of an outcome, as in “precision-guided missile” or “at what precise time will you arrive?” So will precision medicine usher in an age of diagnostic and prognostic certainty?

In fact, the opposite will probably result. The new tools for tailoring treatment will demand a greater tolerance of uncertainty and greater facility for calculating and interpreting probabilities than we have been used to as physicians and patients.

NEJM August 2016

Many genetic variants are rare

Interpretation is laborious and poorlystandardized

Hampers scalabilityand reproducibility

Standardization, data storage for secondaryusage and data sharing are obviousremedies for thesechallenges

Nordic network for standardisation and data sharing

2 workshops in 2016, a third will be in Copenhagen, April 2017

Plan to expand network to: - other leading clinical groups- legal experts- health economy and outcome studies

NORDIC CLINICAL GENOMICS DATA SHARING WORKSHOP 2 21.-22.11.2016

Workshop summary report

Oslo Universitetssykehus

SciLifeLab

Karolinska Universitetssjukhuset

University Hospital Copenhagen (Rigshospitalet)

DNV GL

BigMed• VISION: …«lay the foundation for an ICTplatform that addresses the analytic

bottlenecks for the implementation of precision medicine and paves the way for novel big data analytics. The solutions will provide the patients with an optimized care which takes their unique individual characteristics into proper consideration.”

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Collaboration between health care, academic institutions and industry

Health care

Legal Framework

ICT research Industry

Patient organisations

BIGMED PARTNERS

The case for strengthening nordiccollaboration in personalized medicine

• Nordic added values– Personalized medicine will increase the number of rare diseases – size do

matter

• Individually small countries, together 26 million people

– Collaboration will make it easier to achieve critical mass

– Similar public health care systems

– High patient trust in government and public health care systems

• The timing is perfect– National coordination of efforts to implement personalized medicine are

occuring in all countries

– All countries have, or are about to, establish relevant infrastructures

National Consortium funded by Research Council Norway

The major universities and universityhospitals in Norway are partners

Science for Life Laboratory, Sweden

• National Genomics

Infrastructure (NGI) platform

– Stockholm and Uppsala

– One of largest sequencing

centers in Europe

– Majority of sequencing

technologies available to

support Swedish researchers

• Diagnostics Development

platform

– Healthcare – academia

collaboration

– Facilitate transition of

genomics into clinical routine

Diagnostics Development

National Genomics Infrastructure

SciLifeLab Diagnostics Development platform –Implementing genomics medicine in Sweden

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Healthcare – academia collaborationCovering 80% of the Swedish population

Coordination of genomics medicine on the national level

Clinical Genomics UppsalaCancer diagnostics>1500 cases in clinical routine

Clinical Genomics StockholmRare disease diagnostics using WGS>2000 samples

Clinical Genomics LundBreast cancer NGS diagnostics

Nearly national coverage

Clinical Genomics GothenburgInformatics solutions for healthcare

Petabyte level of storage

Finnish genome strategy

A pilot project could speed up implementation

• We will actively seek funding opportunities for a common nordic sequencing project within thehealth care framework

• Use as instrument for standardisation ofconsenting patients, standardisation of geneticvariant interpretation and data sharing solutions

• The need for a «Genomics Nordic» initiative

Thanks for your attention!