Overview

Biomarkers: Discovery and Development for a Diagnostic Approach to Neurodegenerative Disorders has a focus in biomarkers for neurodegenerative diseases and diagnostic applications in development. Biomarkers have been a heavily studied topic of interest, and recently on the rise is the interest in neurodegenerative disorders. Although there are many techniques used to track neurodegenerative disease progression, this report will primarily focus on blood-based and cerebrospinal fluid-based biomarkers. In addition to covering background information, this report will highlight several technologies that have been developed for employing the use of biomarkers for neurodegenerative disease detection, analysis and therapeutic development. Including substantial background information, illustrated with graphics and figures, this report captures market growth of biomarkers, advantages, disadvantages, and validation techniques.

Three neurodegenerative disorders that are heavily focused on in this report include: Alzheimer’s Disease/Mild Cognitive Impairment, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis. Part II of the report will include all three of these disorders, highlighting specifics including background, history, and development of the disease. Deeper into the chapters, the report will unfold biomarkers under investigation, genetic targets, and an analysis of multiple studies investigating these elements.

Experts interviewed in these chapters include:

• Dr. Jens Wendland, Head of Neuroscience Genetics, Precision Medicine, Clinical Research, Pfizer Worldwide R&D
• Dr. Howard J. Federoff, Executive Vice President for Health Sciences, Georgetown University
• Dr. Andrew West, Associate Professor of Neurology and Neurobiology and Co-Director, Center for Neurodegeneration and Experimental Therapeutics
• Dr. Merit Ester Cudkowicz, Chief of Neurology at Massachusetts General Hospital

Part III of the report makes a shift from neurobiomarkers to neurodiagnostics. This section highlights several diagnostics in play and in the making from a number of companies, identifying company strategies, research underway, hypotheses, and institution goals. Elite researchers and companies highlighted in this part include:

• Dr. Xuemei Huang, Professor and Vice Chair, Department of Neurology; Professor of Neurosurgery, Radiology, Pharmacology, and Kinesiology Director; Hershey Brain Analysis Research Laboratory for Neurodegenerative Disorders, Penn State University-Milton, S. Hershey Medical Center Department of Neurology
• Dr. Andreas Jeromin, CSO and President of Atlantic Biomarkers
• Julien Bradley, Senior Director, Sales & Marketing, Quanterix
• Dr. Scott Marshall, Head of Bioanalytics, and Dr. Jared Kohler, Head of Biomarker Statistics, BioStat Solutions, Inc.

Further analysis appears in Part IV. This section includes a survey exclusively conducted for this report. With over 30 figures and graphics and an in depth analysis, this part features insight into targets under investigation, challenges, advantages, and desired features of future diagnostic applications. Furthermore, the survey covers more than just the featured neurodegenerative disorders in this report, expanding to Multiple Sclerosis and Huntington’s Disease.

Finally, Insight Pharma Reports concludes this report with clinical trial and pipeline data featuring targets and products from over 300 companies working in Alzheimer’s Disease, Parkinson’s Disease and Amyotrophic Lateral Sclerosis.

Executive Summary

Biomarkers: Discovery and Development for a Diagnostic Approach to Neurodegenerative Disorders has a focus in biomarkers for neurodegenerative diseases and diagnostic applications in development. Biomarkers have been a heavily studied topic of interest, and recently on the rise is the interest in neurodegenerative disorders. Although there are many techniques used to track neurodegenerative disease progression, this report will primarily focus on blood-based and cerebrospinal fluid-based biomarkers. In addition to covering background information, this report will highlight several technologies that have been developed for employing the use of biomarkers for neurodegenerative disease detection, analysis and therapeutic development.

Part I of this report includes Chapters 2 and 3, highlighting background information relevant to the rest of the report. Chapter 2 will detail a definition of biomarkers, elaborating on different types used in the clinic, market growth, advantages, disadvantages, and validation techniques. Chapters 3 will give a brief overview of neurodegenerative disorders speaking to the market growth and rise in interest in biomarkers over the years.

Part II of this report includes Chapters 4, 5 and 6, which give great detail to Alzheimer’s Disease, Parkinson’s Disease and ALS, respectively. This part of the report features definitions of each disease, symptoms, genetic markers, and current research. These three neurodegenerative diseases are among the most common experienced by the aging population. Understanding the role of specific proteins, and therefore identifying core biomarkers, is crucial to combating these diseases and leading patients on the road to effective therapeutics and treatment options.

Chapter 4 will kick off with MCI and Alzheimer’s Disease. These two disorders generally go hand-in-hand and have had a significant impairment on the aging generation. Because of the growing number of cases and the detrimental effects of these diseases, there are many researchers tackling MCI and/or Alzheimer’s Disease from all different angles and perspectives. This chapter provides an extensive amount of detail speaking to genetic targets and their use as biomarkers. Experts interviewed for this section include: Dr. Jens Wendland, Head of Neuroscience Genetics, Precision Medicine, Clinical Research, Pfizer Worldwide R&D, and Dr. Howard J. Federoff, Executive Vice President for Health Sciences, Georgetown University. Each of these interviewees discusses their research and how they are advancing the MCI/Alzheimer’s disease field.

Similarly Chapter 5 details a considerable amount with regard to Parkinson’s Disease. As the second leading cause of neurodegeneration in the aging population, researchers are scrambling to find elusive biomarkers that will provide enough information for therapeutic action. Featured in this chapter is an interview with Dr. Andrew West, who speaks about his research and successes with the gene LRRK2.

Finally, Chapter 6 focuses on Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease. Following a similar style to the previous chapters regarding informative background information, this chapter garners a wide spectrum of history, symptoms, and biomarkers under investigation. In this chapter, Dr. Merit Ester Cudkowicz, Chief of Neurology at Massachusetts General Hospital, discusses her progress on discovering biomarkers for therapeutic development and understanding the biology of ALS.

Part III makes the shift from neurobiomarkers to neurodiagnostics. This section includes Chapters 7, 8, 9 and 10. Each chapter provides insight to developing technologies, recent research, hypotheses and institution goals. Elite researchers and companies highlighted in this part include:

• Dr. Xuemei Huang, Professor and Vice Chair, Department of Neurology; Professor of Neurosurgery, Radiology, Pharmacology, and Kinesiology Director; Hershey Brain Analysis Research Laboratory for Neurodegenerative Disorders, Penn State University-Milton, S. Hershey Medical Center Department of Neurology
• Dr. Andreas Jeromin, CSO and President of Atlantic Biomarkers
• Julien Bradley, Senior Director, Sales & Marketing, Quanterix
• Dr. Scott Marshall, Head of Bioanalytics, and Dr. Jared Kohler, Head of Biomarker Statistics, BioStat Solutions, Inc.

Highlights in these chapters include technology status, advantages, pitfalls and exclusive interviews.

Part IV features a survey analysis exclusively done for this report. Qualifying participants worked with neurobiomarkers, neurodiagnostics, or both. With over 30 survey figures depicting the general R&D group working in this space, this section provides information including: research demographics, targets under investigation, challenges, advantages, and desired features of future diagnostic applications.

To add even more to the robustness of this report, Insight Pharma Reports put together a generous amount of data compiling clinical trial information pipeline data related to Alzheimer’s Disease, Parkinson’s Disease and Amyotrophic Lateral Sclerosis.

Table of Contents

Executive Summary

Part I: Introduction and Background Information

Chapter 1: The Focus of this Report

Chapter 2: Biomarkers and Their Clinical Utility
What are Biomarkers?
Advantages of Biomarkers
Clinical Endpoints vs. Surrogate Endpoints
Advantages of Biomarkers as Surrogate Endpoints
Disadvantages to Biomarkers as Surrogate Endpoints
How are Biomarkers Validated?

Chapter 3: Biomarkers in Neurodegenerative Disorders

Part II: Neurobiomarker Discovery and Development

Chapter 4: Mild Cognitive Impairment and Alzheimer's Disease
How is it Related to Alzheimer's Disease?
Conflicting Evidence: Mild Cognitive Impairment or Alzheimer's Disease?
Biomarkers and Candidates for Alzheimer's Disease
Cerebrospinal fluid Analysis vs. Plasma Analysis
Current Biomarkers
Phospholipid Biomarkers
Single Nucleotide Polymorphisms and Apolipoprotein E
Testosterone and Hormone Levels
Interview with Dr. Howard Federoff
Interview with Dr. Jens Wendland

Chapter 5: Parkinson's Disease
What is Parkinson's Disease?
Genetic Factors Linked to Parkinson's Disease
PARK2 (parkin/ubiquitin E3 ligase)
PINK1 (PTEN-induced kinase 1 protein)
GBA (glucocerebrosidase)
Promising Biomarkers for Parkinson's Disease
SNCA (?-synuclein)
PARK7 (DJ-1 protein)
LRRK2 (dardarin protein)
Other biomarkers
Interview with Dr. Andrew West
Research Background
LRRK2 Protein Kinase
Advantages
Challenges and Limitations
Parkinson's Disease Outlook

Chapter 6: Amyotrophic Lateral Sclerosis
What is Amyotrophic Lateral Sclerosis?
Genetic Markers Identifying ALS
SOD1
C9orf72
Fused in Sarcoma (FUS)
TDP-43
Potential Biomarker Candidates for ALS
TDP-43
pNF-H
Cystatin C
Other biomarkers
Interview with Dr. Merit Ester Cudkowicz
Research Background
ALS Research
Research advantages and challenges
ALS outlook

Part III: Neurodiagnostics and Biomarker Technologies

Chapter 7: Neurodiagnostics and Biomarker Technologies

Chapter 8: Penn State Hershey Medical Center
Research Background
MRI for Parkinson's Disease Diagnosis
Interview with Dr. Xuemei Huang
Research Background
Non-Invasive Imaging Tool
Advantages
Challenges and Limitations
Parkinson's Disease Outlook

Chapter 9: Atlantic Biomarkers
Research Background
Mass-Spectrometry Assays for Biomarkers
Impact on Healthcare
Interview with Dr. Andreas Jeromin
Company Background
Neurobiomarker Research
Mass Spectrometry-Based Assays

Chapter 10: Quanterix
Company Background 5
Simoa Science Technology
Expected Impact on Healthcare
Interview with Julien Bradley
Quanterix Background
Simoa Science Technology

Chapter 11: BioStat Solutions, Inc. (BSSI)
Company Background
Statistical Support
Impact on Healthcare
Interview with Dr. Scott Marshall/Dr. Jared Kohler

Part IV: Survey Results

Chapter 12: Survey Results

Part V: Clinical Trials And Pipeline Information

References

About Cambridge Healthtech Institute

List of Tables

Table 2.1: Clinical Applications of Biomarkers as Surrogate Endpoints
Table 4.1: Advantages to using genetics to identify biomarkers
Table 5.1: Symptoms of Parkinson's Disease
Table 13.1 Clinical Trial and Pipeline Data for Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis

List of Figures

Figure 2.1: Growth of Interest in Biomarkers
Figure 2.2: Biomarker Presence in Diagnostic Development vs. Therapeutic Development
Figure 3.1: Comparison of Disease Categories
Figure 3.2: Growth of Interest in Biomarkers for Neurology
Figure 3.3: Growth of Interest in Biomarkers for Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and Parkinson's Disease
Figure 12.1: How Would You Categorize Your Organization?
Figure 12.2: Which Neurodegenerative Condition are You Currently Studying?
Figure 12.3: Which Targets for Huntington's Disease (HD) are You Currently Studying?
Figure 12.4: What is the Clinical Status of Your Target(s) for HD?
Figure 12.5: When Do You Expect Your Targets for HD to Enter Clinical Trials?
Figure 12.6: When Do You Expect Your Target to be an Available Therapeutic for HD?
Figure 12.7: Which Targets for Amyotrophic Lateral Sclerosis (ALS) are You Currently Studying?
Figure 12.8: What is the Clinical Status of Your Target(s) for ALS?
Figure 12.9: When Do You Expect Your Targets for ALS to Enter Into Clinical Trials?
Figure 12.10: When Do You Expect Your Target to be an Available Therapeutic for ALS?
Figure 12.11: Which Targets for Multiple Sclerosis (MS) are You Currently Studying?
Figure 12.12: What is the Clinical Status of Your Target(s) for MS?
Figure 12.13: When Do You Expect Your Targets for MS to Enter Into Clinical Trials?
Figure 12.14: When Do You Expect Your Target for MS to be an Available Therapeutic?
Figure 12.15: Which Signatures for Alzheimer's Disease (AD) are You Currently Studying?
Figure 12.16: What is the Clinical Status of Your Target(s) for AD?
Figure 12.17: When Do You Expect Your Targets for AD to Enter Into Clinical Trials?
Figure 12.18: When Do You Expect Your Target to be an Available Therapeutic for AD?
Figure 12.19: Which Signatures for Parkinson's Disease (PD) are You Currently Studying?
Figure 12.20: What is the Clinical Status of Your Target(s) for PD?
Figure 12.21: When Do You Expect Your Targets for PD to Enter Into Clinical Trials?
Figure 12.22: When Do You Expect Your Targets for PD to be an Available Therapeutic?
Figure 12.23: How Would You Describe Your Line of Research?
Figure 12.24: With Respect to Neurodiagnostics, Which Diagnostic Tools are You Developing for Biomarker Signatures?
Figure 12.25: With Respect to Neurodiagnostics, What are Challenges You Have Encountered with Your Diagnostic Development?
Figure 12.26: With Respect to Biomarker Development, What Tools are You Using to Identify Biomarker Signatures?
Figure 12.27: With Respect to Biomarker Development, What are Challenges You Have Encountered with Your Therapeutic Discovery/Development?
Figure 12.28: With Respect to Biomarker Therapeutics, What Tools are You Using to Identify Biomarker Signatures?
Figure 12.29: With Respect to Biomarker Therapeutics, What are Challenges You Have Encountered with Your Therapeutic Discovery/Development?
Figure 12.30: Which Imaging Techniques do You Feel are the Most Beneficial for Studying the Effects of Neurodegenerative Diseases?
Figure 12.31: Which Therapeutics do You Feel will be the Most Beneficial for Neurodegenerative Diseases?