Biomarkers: Translating Research into Clinical Practice

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1 Biomarkers: Translating Research into Clinical Practice AFTD Education Conference San Diego, April 2015 Nadine Tatton, PhD Scientific Director, AFTD HelpLine u info@theaftd.org u

2 FTD is a spectrum of diseases FTD -Motor Neuron Disease/ALS ALS Behavioral Variant FTD Cognitive loss Behavior impairment Motor symptoms Cognitive loss Disinhibition Inflexibility Decreased insight Cognitive loss Motor symptoms Upper and/or lower motorneuron pathways svppa semantic variant Fluent speech Decreased word comprehension and recognition of objects,people nappa Nonfluent/ agrammatic variant Halting speech Short phrases Grammar errors lvppa logopenic variant Spontaneous but slow speech output Word retrieval problems Cognitive & memory loss Asymmetric rigidity Apraxia Behavioral & cognitive loss Parkinsonism Eye movement disturbances Corticobasal Syndrome Progressive Supranuclear Palsy

3 The FTD spectrum shares proteinopathies and anatomic loci FTD -Motor Neuron Disease/ALS ALS Behavioral Variant FTD FTLD-TDP43 FTLD-FUS Cortex, Motor neurons TDP43,SOD1,FUS Upper, lower MNs FTLD-Tau (3R) FTLD-TDP43 Prefrontal lobe Temporal lobe svppa semantic variant FTLD-TDP43 Frontal/ventral Temporal lobe nappa Nonfluent/ agrammatic variant FTLD-Tau more than FTLD-TDP43 or AD pathology Left posterior frontal Lobe, insula lvppa logopenic variant AD pathology more than FTLD-Tau or TDP43 Left post/supr temporal lobe & Medial parietal FTLD-Tau(4R) more than AD pathology Frontal, temporal lobe, Basal ganglia FTLD-Tau(4R) Basal ganglia Brainstem Corticobasal Syndrome Progressive Supranuclear Palsy

4 What is a biomarker? A biomarker is a distinct biochemical, genetic or molecular characteristic or substance that is an indicator of a biological condition or process

5 What do biomarkers measure? A biomarker can measure the presence or progress of disease or the effects of treatment

6 Why do we need Biomarkers? To support accurate diagnosis To detect early disease changes To follow disease progression To support drug development and measure response to drugs in a clinical trial SHUTTERSTOCK

7 Imaging Biomarkers Diagnosis and Progression of FTD MRI Diffusion Tensor Imaging PET Localize and measure changes in brain structure, function

8 Fluid-based Biomarkers Finding a molecular signature of FTD Cerebrospinal Fluid (CSF) Lumbar puncture Plasma,White Blood Cells Blood draw Adult pluripotent stem cells Skin biopsy Current research is focused on finding sensitive and accurate biomarkers for FTD Gene mutations, specific protein aggregates, molecules secreted by nerve cells

9 Difficult Questions in FTD Diagnosis and Care Is it FTD or Alzheimer s or something else? Which FTD disorder is it? Known gene mutation, familial or sporadic FTD? Is it a tau or a TDP-43 proteinopathy? What stage of the disease early, late?

10 How can you help? You are the most important member of the health care team We need your help to answer the difficult questions in FTD Please join us in building our newest resources

11 ARTFL: Advancing Research and Therapies for FTLD UBC UCSF UCLA UCSD MCR Northwestern WashU Toronto MGH CUMC UPENN JHU UNC MCF

12 LEFFTDS: Longitudinal Evaluation of fftld UBC MCR CUMC UPENN MGH UCSF WashU MCF

13 Coming soon..the FTD Disorders Registry AFTD and The Bluefield Project have partnered to create an FTD registry The registry will be open to persons diagnosed with an FTD disorder, their caregivers and family members The registry will help advance research & drug development and empower our FTD community

14 Thank You!

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