Functional Fluidics at The Foundation for Sickle Cell Disease Research: June 16, 2018

 

Novel Biomarkers and Surrogate Endpoints Clarify Sickle Cell Disease Status and the Effects of Disease-Modifying Therapies.  Saturday June 16 (11am to 12pm)

Moderated by Patrick Hines, MD/PhD


Screenshot 2018-06-15 17.52.59

Overview

The clinical pain and fatigue characteristic of sickle cell disease is difficult to objectively quantify. Clinicians cannot depend on their physical exam, imaging studies, or laboratory data to validate claims of pain by their patients. This challenge often creates physician and patient dissatisfaction, and makes it difficult to assess individual patient response to SCD modifying therapy in clinical trials. Biomarkers associated with cellular adhesion, inflammation, coagulation, anemia/hemolysis, cellular aggregates, microparticles and nitric oxide metabolism may help to objectively assess patient-reported outcomes (PROs) and response to disease modifying therapy. There is an urgent need for validated biomarkers in sickle cell disease that facilitate open communication between the healthcare team, industry, and individuals with SCD. We will highlight the current “state of the art” in the application of biomarkers and surrogate endpoints as applied to SCD in this educational session.

 

Session Objective

1. Learn the principles of functional biomarkers and their applications to sickle cell disease.
2. Learn how novel functional biomarkers can be applied to better understand the relationship between SCD biology, clinical manifestations, and patient experience.
3. Learn how novel biomarkers and surrogate endpoints can be incorporated into clinical trials of SCD-modifying agents.
4. Understand how SCD biomarkers and surrogate endpoints are evaluated from a regulatory perspective.

 

Introductions, Overview of Definitions and Specific Biomarkers Currently Used in SCD Clinical Trials

Patrick Hines, MD/PhD
Associate Professor of Pediatric Critical Care MedicineChildren’s Hospital of Michigan Research Associate, Department of Physiology, WSU School of Medicine Functional Fluidics, Founder and CEO

 

Regulatory Perspective on Biomarkers and Surrogate Endpoints to Evaluate SCD Therapies

Nicole Verdun, MD Director for the Office of Blood Research and Review (Acting) Center for Biologics Evaluation and Research (CBER)
Food and Drug Administration
 

Industry Perspective on Biomarkers and Surrogate Endpoints in SCD Clinical Trials

Ahmed Daak, MD, MSc, Ph.D.

Vice President of Medical Research and Clinical Development Sancilio Pharmaceuticals Company (SCI)
Research Professor
Center of Molecular Biology and Biotechnology (CMBB) Florida Atlantic University (FAU)

 

No other contract research company has more experience performing blood function assays to evaluate anti-adhesive therapies in Sickle Cell Disease than Functional Fluidics.

Overview

This short video describes the origins of the company, based on research in the Hines Lab at Wayne State University. We have developed a suite of assays that address the need for better ways to assess blood function, starting with the experience of Dr. Hines as a Pediatric ICU Physician at Detroit Medical Center.

Assays At A Glance

The following is a list of standardized assays that we offer. Please click on any description for more information.

Flow Adhesion

Blood samples (whole or isolated cellular components) at baseline or following drug treatment (single dose or dose response) are subjected to physiologic flow across an adhesive substrate of interest. Adhered cells are quantified to generate an adhesion index (AI).

Flow Thrombosis

Blood samples (whole or isolated platelets) are pre-treated with a drug of interest, and then subjected to physiologic arterial flow across a substrate of interest. A series of photomicrographs of fluorescently labeled blood (see Figure 3) is analyzed to determine the kinetics of thrombosis formation (lag time, max rate of thrombosis, area under the curve, and maximum amplitude).

Flow Adhesion Dynamic

Blood samples (whole or isolated cellular components) at baseline or following drug treatment (single dose or dose response) are subjected to physiologic flow across an adhesive substrate of interest (usually selectins). Time-lapse images are acquired to measure cell rolling / sliding along the channel surface. Mean velocity for rolling objects and cell flux is measured to generate a dynamic adhesion index (dAI).

Flow Adhesion Dynamic

Blood cells are adhered to a substrate of interest (see Flow Adhesion), followed by introduction of anti-adhesive drug under flow. Remaining adherent cells are measured to generate a reverse adhesion index (rAI).

Flow Adhesion Characterization

Adhered cells are fixed with 4% formalin and stained following an adhesion assay (FF-FA, FF-FAR, FF-FAA). Fluorescence microscopy is utilized to differentiate between and quantify specific cell populations.

Flow Adhesion Avidity

Blood cells are adhered to a substrate of interest (see Flow Adhesion), followed by introduction of sequentially increased shear. Remaining adherent cells are quantified followed by a sequential increase in shear (5, 10, and 20 dyne/cm^2), to generate an avidity adhesion index (aAI).

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