Transcript AD biomarker introduction- Annemieke Aartsma

Biomarker introduction
Annemieke Aartsma-Rus
November 7 2015
What is a biomarker?
A biomarker is a characteristic that is objectively
measured and evaluated as an indicator of normal
biological processes, pathogenic processes or
pharmacological responses to a therapeutic
intervention
Annemieke Aartsma-Rus
Different types of biomarkers
• Diagnostic biomarkers
• Something is wrong
• Prognostic biomarkers
• Predict disease course mild/severe
• Therapeutic monitoring biomarkers
• Predict whether therapy will work/is working
• Sometimes one biomarker is both diagnostic and
prognostic and monitoring but generally NOT
Annemieke Aartsma-Rus
Biomarkers used in DMD already
• Diagnostic biomarkers
• Serum creatine kinase (CK)
• Elevated in DMD at young age
• Not disease specific
• Indication of muscle damage
• Helps clinicians to make differential diagnosis
• Gene analysis needed to confirm diagnosis
(DMD mutation)
Annemieke Aartsma-Rus
Biomarker research for DMD
• Prognostic biomarkers
• May allow stratification in trials
• Research ongoing
• DNA differences (SNPs) in genes involved in
inflammation can influence age at loss of
ambulation
• Osteopontin
• LTBP4
• Challenges:
• Which genes to focus on?
• Large cohorts needed to confirm findings
Annemieke Aartsma-Rus
Biomarker research for DMD
• Therapeutic biomarkers
• Used for therapeutic monitoring of treatment
• Identify responders
• Before trial (more homogeneous population)
• During trial (to continue with responders)
• Pharmacodynamic biomarker
• Surrogate endpoint
Annemieke Aartsma-Rus
Biomarker research for DMD
• Pharmacodynamic biomarker
• Did the treatment work as proposed?
• Confirmation drug mechanism
• E.g. dystrophin restoration for exon
skipping/ataluren or reduced fibrosis for
antioxidant
Annemieke Aartsma-Rus
Biomarker research for DMD
• Surrogate endpoints
• Correlates with clinical benefit (now or in future)
• A tool that can be used to accelerate the process
of making the drug available on the market
• Advantage: may be quicker and less prone to
variation/motivation than functional tests
• No surrogate endpoint available yet for DMD
Annemieke Aartsma-Rus