As advances in omics technologies enable the development of high value molecular diagnostics, neurological conditions represent an attractive target for diagnostic companies. In this report, Datamonitor identifies the diseases in which early detection with a biomarker could significantly benefit the patient, gain payer approval, and ultimately expand the pharmaceutical market.

Scope

Neurological conditions covered: Alzheimer' s disease, Parkinson' s disease, MS, epilepsy, migraine, insomnia, Huntington' s disease and ALS.
Overview of key biomarkers in development for each condition (including genetics).
Identification of key factors required for the commercial success of neurological diagnostic biomarkers.
Analysis of potential drug revenue gains due to improved diagnostics in Alzheimer' s disease.

Highlights

A battery or algorithm of tests for each disease is likely to be available within the next 10 years. This is already the case for multiple sclerosis, the most mature neurological diagnostic market, with both clinical, imaging and in vitro diagnostics incorporated in a clear algorithm.

Revenue gained from earlier use (identification and incorporation of mild cognitively impaired patients) of potentially disease-modifying drugs in Alzheimer' s disease could generate an additional $5 billion by 2017 across the seven major markets (US, Japan, France, Germany, Italy, Spain and the UK).

Neurology biomarker discovery and development is an attractive market for small biotechnology companies. The regulation of in vitro diagnostics is significantly less stringent than for pharmaceutical drugs. This decreases the considerable financial barriers to entry usually faced by biotechnology companies orientated towards drug discovery.

Reasons to Purchase

Assess which diseases have the highest unmet need for new biomarkers.
Appreciate the lucrative potential of earlier treatment of neurodegenerative conditions.
Forecast the impact of improved diagnostics on neurological drug sales.

ABOUT DATAMONITOR HEALTHCARE
- About the CNS pharmaceutical analysis team
CHAPTER 1 EXECUTIVE SUMMARY
- Scope of the analysis
- Contributing experts
- Datamonitor insight into diagnostics in neurology
- Related reports
CHAPTER 2 BACKGROUND
- What is a diagnostic test?
  - Biomarkers - objective measures
- Regulation of diagnostics
  - Imaging
  - In vitro diagnostics
    - European Union
    - United States
- The value of a diagnostic test
  - Technical performance
  - Clinical performance
  - False positives and false negatives
CHAPTER 3 CURRENT DIAGNOSTIC TECHNIQUES AND CHALLENGES
- Neurological conditions - differing disease pathophysiology influences biomarker unmet need
  - Delay to accurate diagnosis is particularly slow in Alzheimer' s disease at present
- Alzheimer' s disease
  - Challenges for Alzheimer' s disease biomarkers
    - Proposed criteria for effective biomarkers in Alzheimer' s disease
  - Current diagnostic criteria
    - DSM-IV-TR
    - NINCDS-ADRDA
    - Recent revising suggestion - aiming for earlier detection
  - Functional tests
    - Mini-Mental Status Exam
    - Ruling out other conditions
  - Pathological diagnosis post-mortem
  - Time to accurate diagnosis of Alzheimer' s disease
- Parkinson' s disease
  - Diagnosis is based on clinician observation of symptoms
    - Primary symptoms used for diagnosis
    - Neurological evaluation of Parkinson' s disease
    - Ruling out disorders that produce parkinsonian symptoms
  - Current imaging techniques used by neurologists
  - Time to accurate diagnosis of Parkinson' s disease
- Multiple sclerosis
  - Current diagnostic technique includes MRI scans
  - Magnetic resonance imaging
    - Clinical signs and MRI might be enough for diagnosis
  - Spinal tap
  - Evoked Potential Tests
  - Differential diagnosis
  - Time to accurate diagnosis of multiple sclerosis
- Epilepsy
  - Patient and family reported signs
  - Electroencephalography
    - Portable EEG
  - Magnetic Resonance Imaging
  - Genetic testing
- Migraine
- Insomnia
  - Basic requirements
    - Optional requirements
  - Clinical history
  - Sleep history
  - Polysomnography
- Huntington' s disease
  - Pre-symptomatic diagnosis, but no disease-modifying treatment
    - Predictive genetic test is available, but use is only moderate
    - Pre-implantation screening is rarely undertaken
- Amyotrophic lateral sclerosis
  - The El Escorial diagnostic criteria
CHAPTER 4 IMPACT OF FUTURE DEVELOPMENTS
- Future disease diagnosis
  - Alzheimer' s disease
    - Future diagnostic algorithm likely to include several biomarkers
  - Parkinson' s disease
    - Disease-modifying drug will stimulate early diagnostics research
  - Multiple sclerosis
    - Comparatively mature diagnostic market with several biomarkers
  - Epilepsy
    - Patient reported events and electroencephalography (EEG) likely to remain the mainstay of diagnosis
  - Migraine and insomnia
  - Amyotrophic lateral sclerosis
- Molecular biomarkers present high value market for diagnostic companies
  - Imaging companies
  - Genetic testing companies
  - In vitro assay companies
- Benefit to pharmaceutical companies is substantial
  - Defined patient population leads to more targeted marketing
  - Earlier treatment results in greater revenues
  - Case studies-quantifying the impact of improved biomarkers on drug sales
    - Huntington' s disease-pre-symptomatic "at risk" population-the lucrative untapped market
    - Alzheimer' s disease-incorporation of patients with mild cognitive impairment
- Benefit to patients is significant
  - Earlier treatment and pre-symptomatic medicine
  - Personalized medicine
  - More sophisticated drug development
- Payers will welcome the clarity biomarkers offer
CHAPTER 5 FUTURE IMAGING TECHNOLOGIES
- Definitions
- Alzheimer' s disease and mild cognitive impairment
  - Structural imaging
  - Radiotracer fluorodeoxyglucose
  - Beta-amyloid proves to be the dominant imaging biomarker
    - Beta-amyloid radioligands using PET scans
    - GE Healthcare' s Pittsburgh Compound-B
    - Other beta-amyloid tracers
  - Acetylcholinesterase
- Parkinson' s disease
  - Radiotracers
    - GE Healthcare' s DaTSCAN
  - Transcranial sonography
- Other neurological diseases
  - Epilepsy
  - Multiple sclerosis
CHAPTER 6 FUTURE IN VITRO DIAGNOSTIC TESTS
- Summary
- Serum- and urine-based biomarkers (including genomics)
  - Alzheimer' s disease and mild cognitive impairment
    - Power3' s NuroPro protein serum biomarkers
    - Proteome Sciences' TMT technology mass spectrometry tool for protein biomarker development
    - Nymox Pharmaceutical' s AlzheimAlert urine test
    - Genetic blood testing-DiaGenic and IMGM Laboratories
    - Pronucleon peptides, fluorescently labeled peptides for amyloid detection-Adlyfe
    - Sulfatide, possible specificity for mild Alzheimer' s disease
    - Genomics, genetic susceptibility of sporadic form is becoming clear-Athena Diagnostics and others
  - Parkinson' s disease
    - Neuromelanin-endogenous pigment identifies Parkinson' s disease
    - Genomics, genetic susceptibility of sporadic form is becoming clear-Athena Diagnostics and others
    - Power 3' s NuroPro
  - Multiple sclerosis
    - Anti-glycan antibodies in early stage patients-Glycominds
    - Plasma markers of the disease and Tysabri side effect-BG Medicine
    - Genomics in multiple sclerosis
  - Amyotrophic lateral sclerosis
    - Genomics of ALS-attention shifts to sporadic form
  - Other neurological diseases
- Cerebrospinal fluid
  - Alzheimer' s disease (AD)
    - Beta-amyloid and tau levels have been extensively studied
    - Isoprostane-8,12-iso-iPF2a-VI
  - Parkinson' s disease
    - Neurofilament heavy-chain' s expose axonal damage
  - Other neurological conditions
    - Amyotrophic lateral sclerosis
    - Multiple sclerosis
BIBLIOGRAPHY
- Journal papers and conference abstracts
- Websites
- Datamonitor reports
APPENDIX
- Contributing experts
- About Datamonitor
  - About Datamonitor Healthcare
- Datamonitor Healthcare' s therapy area capabilities
  - About the Disease analysis team
  - Disclaimer
List of Tables
- Table 1: Comparative biomarker potential across key neurological diseases
- Table 2: DSM-IV criteria for Alzheimer' s disease type dementia
- Table 3: Unified Parkinson' s Disease Rating Scale-cognition, behavior and mood
- Table 4: New multiple sclerosis diagnostic criteria (McDonald criteria)
- Table 5: Prevalence rate of mild cognitive impairment (MCI)
- Table 6: A(1-42 in cerebrospinal fluid
List of Figures
- Figure 1: Typical diagnostic biomarker development process
- Figure 2: Distribution graph of biomarker accuracy
- Figure 3: False positives and false negatives - distribution curve
- Figure 4: Mean time between initial presentation to accurate diagnosis of Alzheimer' s disease, Parkinson' s disease and multiple sclerosis
- Figure 5: Time (months) from presentation to accurate diagnosis of Alzheimer' s disease, 2006
- Figure 6: Percentage of neurologists using each diagnostic imaging technique to make a diagnosis of Parkinson' s disease, 2007
- Figure 7: Time (months) from presentation to accurate diagnosis of Parkinson' s disease, 2007
- Figure 8: Current diagnostic algorithm for multiple sclerosis
- Figure 9: MRI scan image of a multiple sclerosis patients brain, and a normal individual
- Figure 10: Magnetic resonance imaging (MRI) scanner
- Figure 11: Time (months) from presentation to accurate diagnosis of multiple sclerosis (MS), 2006
- Figure 12: An electroencephalograph (EEG)
- Figure 13: Photograph of a portable eletroencephalography (EEG) unit
- Figure 14: Genetic risk of developing Huntington' s disease
- Figure 15: Points of diagnosis of Alzheimer' s disease
- Figure 16: Revenue gain in the Alzheimer' s disease market value with the inclusion of patients with amnestic mild cognitive impairment (amMCI), 2013-17