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T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
ACADEMIC RESEARCH INDUSTRY
PUBLIC-PRIVATE PARTNERSHIPS FOR NEW INNOVATIONS
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T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
PHARMA R&D SPEND
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
Important decisions in drug discovery
Target Selection
and Validation
Screening Pre-clinical Phase I Phase II Phase III Phase IV
What Target?
Which Patients?
The Problem:
It difficult to develop novel therapies that differentiate from standard of care
>90% of compounds in clinical trials fail due to lack of safety and efficacy
Picking the right target is the most important decision we make
Sally John, Biogen
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
Very large collections combining genome data with health data is needed
DATA RESOURCE WITH GENOME AND HEALTH
INFORMATION
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
OPPORTUNITY FOR MULTIPLE STUDY DESIGNS
POPULATION ISOLATE
HEALTHREGISTERS
BIOBANKS GENOME DATA
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T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
Toimimaton geeni
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
Suojaavat Geenit
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
EARLY SETTLEMENT • 2000-10 000 years ago• South and Coast
LATE SETTLEMENT• 16th century• multiple bottle necks
EXPANSION • 18th century – population 250 000• Today – population 5.4 million
EARLYSETTLEMENT
LATESETTLEMENT
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
Opportunity to identify disease associated low frequency variants
Population isolate
• Finns have dramatically fewer rare DNA variants than other Europeans
• Some specific DNA variants jump to unusually high frequencies
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
Two LPA LoF variants(35 000 Finns)
LoF variant Frequency in Finns Frequency in non Finns
LPA1(4974) 2.8% 0.47%
LPA2(4289) 4.8% 3.6%
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
Loss-of-function variants in LPA protects from Coronary Heart Disease
Finnish enriched DNA variant lowers LPA levels
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
Loss-of-function variants in LPA protects from Coronary Heart Disease
Each copy of LPA lowering variant lowers CHD risk by 15-20%
Finnish enriched DNA variant lowers LPA levels
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
Two LPA LoF variants(35 000 Finns)
LoF variant Frequency in Finns Frequency in non Finns
LPA1(4974) 2.8% 0.47%
LPA2(4289) 4.8% 3.6%
227 Finns homozygous/compound het
Linking to National Health Records
No sign of increased morbidity
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
Truncating mutations in SLC30A8 seen 3x more often in healthy controls than diabeticsSTRONG protection against diabetes !!!
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
50% of all known Finnish R138X carriers are around Jakobstad
And 12, i.e. 50% of them, seem to have a connection to an island called Larsmo
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
Recalling SLC30A8 carriers
• More than 75% of individuals recalled have returned for extensive phenotypinginvolving a test meal and numerous blood draws over three hours
• 73 individuals already successfully studied under this protocol
• Almost all are healthy controls with no self-interest in the research
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
These provide precise clues to interventions that could be safe and effective
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
OPPORTUNITY FOR MULTIPLE STUDY DESIGNS
POPULATION ISOLATE
HEALTHREGISTERS
BIOBANKS GENOME DATA
+ + +
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
NATIONAL REGISTERS
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
EXAMPLE OF HEALTH HISTORIES FROM TWO PERSONS FROM THE NATIONAL BIOBANKS WITH A 40 YEAR FOLLOW-UP
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
OPPORTUNITY FOR MULTIPLE STUDY DESIGNS
POPULATION ISOLATE
HEALTHREGISTERS
BIOBANKS GENOME DATA
+ + +
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
BIOBANK ACT + SOCIAL SECURITY NUMBER
BIOBANK
CLINICAL STUDIES
RECALLING
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
IPHG
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
IPHG-hanke• Tutkitaan noin 30 pharma kollaboraattorien valitsemaa
geeniä• Finrisk, Terveys 2000, HBCS, Laseri (Young Finns), NFBC
kohortit (yht noin 30 000 henkilöä)• Hilmo, Avo-hilmo, Kela reseptilääkerekisteri, syöpärekisteri,
kuolinsyyrekisteri• Ei mitään datan tuottoa, käytetään vain olemassa olevaa
dataa• Kaikki fenotyyppejä sisältävä analysointi tehdään
Suomessa, kollaboraattorit saavat ainoastaananalyysituloksia, ei yksilökohtaista tietoa
IPHG-hankkeen kokemuksia
- Innostava pilotti, joka stimuloinut FinnGenin jauusia partnereita (Astra-Zeneca)
- Liian pieni näytekoko - > tarvitaan suurempimateriaali
- Teknistä datan harmonisointia
- KELA tiedot raahaavat auttamattomasti perässä, toivottoman hidasta päivittää tietoja
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
• Maailmassa lukuisia biopankkeja ja hyviä keräyksiä
• Lukuisat toimijat ovat aloittaneet biopankkien tehokkaan
rakentamisen
• Meillä vahvuuksia, mutta niihin ei voi tuudittautua
• Ministeriöiden vuosien kova työ ja tuoreet poliittiset päätökset
tärkeitä viestejä kansainväliselle kentälle
EMME OLE AINOA MAHDOLLISUUS
T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N
