• Biospecimen SolutionsPrecision Value & HealthCareers
    P_ForMedicine_no_tag_RGBP_ForMedicine_no_tag_RGBP_ForMedicine_no_tag_RGBP_ForMedicine_no_tag_RGB
    • Clinical
      Trial Services
        • Overview
            • Oncology Clinical TrialsImage

              Oncology Clinical Trials


              Through 20+ years running successful oncology trials, we’ve developed a unique blend of proprietary technologies, flexible processes, and creative problem solving abilities that advance even the most challenging clinical development programs.

              • Rare & Orphan DiseaseImage

                Rare & Orphan Disease


                With experience built on 150+ orphan disease projects covering 80+ rare diseases, we know how to anticipate logistical and regulatory obstacles and craft bold solutions that drive rare disease development programs.

        • Global Clinical Trial Support –
            • North & South America –
              • Oncology Clinical TrialsImage

                Oncology Clinical Trials


                Through 20+ years running successful oncology trials, we’ve developed a unique blend of proprietary technologies, flexible processes, and creative problem solving abilities that advance even the most challenging clinical development programs.

            • Europe –
              • Oncology Clinical TrialsImage

                Oncology Clinical Trials


                Through 20+ years running successful oncology trials, we’ve developed a unique blend of proprietary technologies, flexible processes, and creative problem solving abilities that advance even the most challenging clinical development programs.

            • APAC –
              • Oncology Clinical TrialsImage

                Oncology Clinical Trials


                Through 20+ years running successful oncology trials, we’ve developed a unique blend of proprietary technologies, flexible processes, and creative problem solving abilities that advance even the most challenging clinical development programs.

        • Clinical Trial Management –
            • Study Start-up & Feasibility –
              • Oncology Clinical TrialsImage

                Oncology Clinical Trials


                Through 20+ years running successful oncology trials, we’ve developed a unique blend of proprietary technologies, flexible processes, and creative problem solving abilities that advance even the most challenging clinical development programs.

            • Project Management –
            • Patient Recruitment –
            • Personalized Clinical Trial Operations –
            • Biometrics –
            • Medical & Safety Monitoring –
            • Clinical Data Management –
            • Medical Writing –
        • Clinical Development Strategy –
            • Clinical Development Planning –
              • Oncology Clinical TrialsImage

                Oncology Clinical Trials


                Through 20+ years running successful oncology trials, we’ve developed a unique blend of proprietary technologies, flexible processes, and creative problem solving abilities that advance even the most challenging clinical development programs.

            • Biomarker Strategies –
            • Cell & Gene Therapy Strategies –
            • CDx Regulatory and Market Access –
        • Clinical Trial Design –
            • Basket & Umbrella Trials –
              • Oncology Clinical TrialsImage

                Oncology Clinical Trials


                Through 20+ years running successful oncology trials, we’ve developed a unique blend of proprietary technologies, flexible processes, and creative problem solving abilities that advance even the most challenging clinical development programs.

            • Biomarker Clinical Trials –
            • Master Protocol Trials –
            • Decentralized Clinical Trials
        • Biostatistics –
            • Statistical Consulting –
              • Oncology Clinical TrialsImage

                Oncology Clinical Trials


                Through 20+ years running successful oncology trials, we’ve developed a unique blend of proprietary technologies, flexible processes, and creative problem solving abilities that advance even the most challenging clinical development programs.

            • Study Design –
            • Data Monitoring Committees –
            • CDISC Programming and Documentation –
            • eCTD Submissions –
        • Central Lab Services –
            • Clinical Specimen Kitting –
              • Oncology Clinical TrialsImage

                Oncology Clinical Trials


                Through 20+ years running successful oncology trials, we’ve developed a unique blend of proprietary technologies, flexible processes, and creative problem solving abilities that advance even the most challenging clinical development programs.

            • Sample Processing –
            • Global Specimen Logistics and Biostorage –
            • Biospecimen Data Services –
            • Precision Lab e-Portal –
            • Virtual Sample Inventory Management –
        • Training
            • Oncology Clinical TrialsImage

              Oncology Clinical Trials


              Through 20+ years running successful oncology trials, we’ve developed a unique blend of proprietary technologies, flexible processes, and creative problem solving abilities that advance even the most challenging clinical development programs.

              • Rare & Orphan DiseaseImage

                Rare & Orphan Disease


                With experience built on 150+ orphan disease projects covering 80+ rare diseases, we know how to anticipate logistical and regulatory obstacles and craft bold solutions that drive rare disease development programs.

    • Lab
      Services
        • Central Lab Services –
            • Clinical Specimen Kitting –
              • Oncology Clinical TrialsImage

                Oncology Clinical Trials


                Through 20+ years running successful oncology trials, we’ve developed a unique blend of proprietary technologies, flexible processes, and creative problem solving abilities that advance even the most challenging clinical development programs.

            • Sample Processing –
            • Global Specimen Logistics and Biostorage –
            • Biospecimen Data Services –
            • Precision Lab e-Portal –
            • Virtual Sample Inventory Management –
        • Specialty Lab Services Overview –
            • Immune MonitoringImage

              Immune Monitoring


              Leverage sophisticated immune monitoring approaches, including flow cytometry, Epiontis ID immune cell phenotyping, and cytokine profiling, to characterize the immune cells in your samples and understand their impact on patient biology.

              • Tissue & Liquid BiopsyImage

                Tissue and Liquid Biopsy


                Obtain a detailed molecular view into patient biology with a range of tissue and liquid biopsy technologies, including our proprietary ApoStream platform which can isolate and enrich circulating tumor cells for downstream analysis.

        • EU Contract Research Organization –
        • Immune Monitoring –
            • Immune Monitoring by Flow Cytometry –
              • Immune MonitoringImage

                Immune Monitoring


                Leverage sophisticated immune monitoring approaches, including flow cytometry, Epiontis ID immune cell phenotyping, and cytokine profiling, to characterize the immune cells in your samples and understand their impact on patient biology.

            • Immune Cell Phenotyping by Epiontis ID –
            • Cytokine Profiling –
            • Gene Expression Profiling –
            • ELISpot and FluoroSpot –
            • Custom Assays –
        • Flow Cytometry –
            • Immune MonitoringImage

              Immune Monitoring


              Leverage sophisticated immune monitoring approaches, including flow cytometry, Epiontis ID immune cell phenotyping, and cytokine profiling, to characterize the immune cells in your samples and understand their impact on patient biology.

              • Tissue & Liquid BiopsyImage

                Tissue and Liquid Biopsy


                Obtain a detailed molecular view into patient biology with a range of tissue and liquid biopsy technologies, including our proprietary ApoStream platform which can isolate and enrich circulating tumor cells for downstream analysis.

        • Genomics –
            • NanoString Assays –
              • Immune MonitoringImage

                Immune Monitoring


                Leverage sophisticated immune monitoring approaches, including flow cytometry, Epiontis ID immune cell phenotyping, and cytokine profiling, to characterize the immune cells in your samples and understand their impact on patient biology.

            • ddPCR –
            • qPCR –
            • NGS –
            • Fluorescence In Situ Hybridisation (FISH) / ISH –
        • Tissue & Liquid Biopsy –
            • ApoStream – CTC and Rare Cell Isolation for Liquid Biopsy
              • Immune MonitoringImage

                Immune Monitoring


                Leverage sophisticated immune monitoring approaches, including flow cytometry, Epiontis ID immune cell phenotyping, and cytokine profiling, to characterize the immune cells in your samples and understand their impact on patient biology.

            • CTC / cfDNA / Exosome Analysis –
            • Multiplex Immunofluorescence –
            • Immunohistochemistry –
            • Fluorescence In Situ Hybridisation (FISH) / ISH
            • Pathology Services –
            • NanoString Assays
        • Bioanalytical Testing –
            • Immunogenicity Testing –
              • Immune MonitoringImage

                Immune Monitoring


                Leverage sophisticated immune monitoring approaches, including flow cytometry, Epiontis ID immune cell phenotyping, and cytokine profiling, to characterize the immune cells in your samples and understand their impact on patient biology.

            • PK Assays –
            • ADA Assays –
            • MesoScale Discovery (MSD) Assays –
            • Quanterix SIMOA –
            • ELISA
        • Cytokine Analysis –
            • ELISA –
              • Immune MonitoringImage

                Immune Monitoring


                Leverage sophisticated immune monitoring approaches, including flow cytometry, Epiontis ID immune cell phenotyping, and cytokine profiling, to characterize the immune cells in your samples and understand their impact on patient biology.

            • MesoScale Discovery (MSD) Assays
            • Luminex –
            • Quanterix SIMOA
        • Preclinical Target and Biomarker Validation –
            • Cell Based Assays –
            • Target Expression – XpressWay Profiles –
            • Tissue Cross-Reactivity –
            • Fluorescence In Situ Hybridisation (FISH) / ISH –
            • Multiplex Immunofluorescence –
            • Immunohistochemistry (IHC)
        • Biospecimens
            • Immune MonitoringImage

              Immune Monitoring


              Leverage sophisticated immune monitoring approaches, including flow cytometry, Epiontis ID immune cell phenotyping, and cytokine profiling, to characterize the immune cells in your samples and understand their impact on patient biology.

              • Tissue & Liquid BiopsyImage

                Tissue and Liquid Biopsy


                Obtain a detailed molecular view into patient biology with a range of tissue and liquid biopsy technologies, including our proprietary ApoStream platform which can isolate and enrich circulating tumor cells for downstream analysis.

    • Data
      Sciences
        • Overview
            • BiostatisticsImage

              Biostatistics


              Seasoned biostatisticians and statistical programmers support every phase of your trial, from study design for small, rare disease trials to regulatory submissions, all backed by meticulous documentation.

              • Computational BiologyImage

                Computational Biology


                Domain experts from our QuartzBio team utilize integrated and harmonized data and tailored AI solutions to drive preclinical and clinical development, including patient stratification, signature development, predictive modeling of drug response, and MOA characterization.

        • Biostatistics
        • Clinical Data Management
        • Biometrics
        • QuartzBio –
            • Biomarker Data Management –
              • BiostatisticsImage

                Biostatistics


                Seasoned biostatisticians and statistical programmers support every phase of your trial, from study design for small, rare disease trials to regulatory submissions, all backed by meticulous documentation.

            • Virtual Sample Inventory Management –
    • Diagnostics
      & CDx
        • IVD and CDx Regulatory Affairs Consulting –
          • spevialty_labs_slice-300×54Image

            Specialty Lab Services


            Our comprehensive approach starts with a foundation of expertise in key biomaker discovery and analysis methods such as immune monitoring, genomics, and bioanalysis.

        • COVID-19 & Viral Panel Assays –
          • spevialty_labs_slice-300×54Image

            Specialty Lab Services


            Our comprehensive approach starts with a foundation of expertise in key biomaker discovery and analysis methods such as immune monitoring, genomics, and bioanalysis.

        • Biospecimens Solutions 
          • spevialty_labs_slice-300×54Image

            Specialty Lab Services


            Our comprehensive approach starts with a foundation of expertise in key biomaker discovery and analysis methods such as immune monitoring, genomics, and bioanalysis.

        • Diagnostic Market Access Services –
          • spevialty_labs_slice-300×54Image

            Specialty Lab Services


            Our comprehensive approach starts with a foundation of expertise in key biomaker discovery and analysis methods such as immune monitoring, genomics, and bioanalysis.

        • Companion Diagnostics
    • Therapeutic
      Areas
        • Overview
            • By Specialty Area
              • Global-clinical-trial-support-2Image

                Global Clinical Trial Support


                Sample processing labs, clinical trial sites and offices in five continents provide the clinical reach and scale to manage complex global programs.

            • Oncology and Immuno-Oncology
              • Oncology Clinical Trials
            • Rare & Orphan Disease
              • Global-clinical-trial-support-2Image

                Global Clinical Trial Support


                Sample processing labs, clinical trial sites and offices in five continents provide the clinical reach and scale to manage complex global programs.

            • Cell & Gene Therapy
              • Cell Therapy
              • Gene Therapy
              • Cell and Gene Therapy Manufacturing
            • CNS & Neuroscience
              • Global-clinical-trial-support-2Image

                Global Clinical Trial Support


                Sample processing labs, clinical trial sites and offices in five continents provide the clinical reach and scale to manage complex global programs.

            • COVID-19
            • AutoImmune & Allergy
            • Pediatric
        • By Research Phase
        • Preclinical Development –
        • Early Phase Trials (I-IIa) –
        • Late Phase Trials (IIb-III) –
    • News &
      Insights
        • Blog –
            • iStock-945738094Image

              Blog


              Industry trends and best practices from Precision experts

              • shutterstock_1033743346Image

                Resources


                A searchable hub featuring the latest Precision case studies, white papers, capabilities brochures and more.

        • Resources –
        • Thought Leadership –
        • News –
            • iStock-945738094Image

              Blog


              Industry trends and best practices from Precision experts

              • shutterstock_1033743346Image

                Resources


                A searchable hub featuring the latest Precision case studies, white papers, capabilities brochures and more.

        • Events –
            • iStock-945738094Image

              Blog


              Industry trends and best practices from Precision experts

              • shutterstock_1033743346Image

                Resources


                A searchable hub featuring the latest Precision case studies, white papers, capabilities brochures and more.

    • About
      Us
        • Our Passion –
            • Patient RecruitmentImage

              Our Passion


              What we do, why we do it and the principles that guide us every day.

              • meet-our-peopleImage

                Meet Our People


                We are devoted professionals with deep expertise in translational science, clinical trials and data sciences.

        • Meet Our People –
        • Careers
        • Regulatory Information –
            • Patient RecruitmentImage

              Our Passion


              What we do, why we do it and the principles that guide us every day.

              • meet-our-peopleImage

                Meet Our People


                We are devoted professionals with deep expertise in translational science, clinical trials and data sciences.

    • Contact
      Us
    • Home
    • Advancing the Use of Biomarkers in CNS Drug Discovery and Development
    Blog Clinical Research Insights Translational & Lab Insights
    Article

    Advancing the Use of Biomarkers in CNS Drug Discovery and Development

    Written By Tracey Owens, Vincent Shortino • March 9, 2023 • 5 min. read

    Understanding the potential of biomarkers in CNS conditions

    The prevalence and burden of central nervous system (CNS) diseases worldwide is high and increasing, in part due to the aging of the global population. Despite significant unmet need, discovery and development for CNS disorders has been largely unsuccessful. Even with advances in our understanding of the underlying mechanisms of CNS conditions, the attrition rate of drugs in development remains elevated. This attrition is primarily driven by failure to show efficacy, and, in many cases, researchers are not even able to confirm that the investigational product reached its intended target for action.

    As in other therapeutic areas, molecular biomarkers have the potential to revolutionize the development of novel treatments for neurological diseases. However, to date, there are few reliable, measurable biomarkers of mental disorders, even though these conditions account for a larger burden of disease than all cancers combined. Of the biomarkers that have been validated, many require invasive procedures or specialized equipment. Identification and validation of new biomarkers would contribute to new drug development, accelerating targeted discovery and enhancing the likelihood of clinical success.

    Role of biomarkers in CNS drug discovery and development

    For most CNS clinical trials, primary endpoints are based on subjective, and often cumbersome, clinician-rated outcome measures that frequently require training or certification prior to administration. The inherent subjectivity of existing efficacy assessments underscores the need for validated biomarkers that can be objectively measured.

    Neuroimaging-based biomarkers have played an important role in CNS drug development and have even been used to assist in determining dosing of investigational new drugs (INDs) with novel mechanisms and targets.1 In addition, cerebrospinal fluid (CSF) immunophenotyping—which can be used to assess immune cell phenotypes and evaluate the biological of intrathecal inflammatory processes—has demonstrated potential in guiding immunotherapeutic selection and monitoring treatment efficacy.

    The advent of technologies to support genomic, proteomic, and metabolomic interrogation of CNS tissues, CSF, or blood has helped to drive discovery of new CNS biomarkers, but challenges remain. In chronic progressive and relapsing neurodegenerative disease, biomarker identification and validation may be difficult because the underlying degenerative process may be so slow that the biomarker is released only in minute quantities. It may also be hard to differentiate acute, new damage from existing background damage.2 Moreover, pathological processes in the CNS are not always reflected in the systemic compartments, so plasma and serum biomarkers may not be available, limiting clinical feasibility.

    Biomarkers under investigation in CNS clinical trials

    To date, the use of CNS biomarkers in clinical trials has been most prevalent in studies of Alzheimer’s disease (AD), multiple sclerosis (MS), and Parkinson’s disease (PD).

    Alzheimer’s disease

    Given that there is currently no cure for AD, early prediction is important because neuronal loss is often already present at the time of diagnosis. Available biomarkers for AD include neuroimaging, such as magnetic resonance imaging (MRI) and position emission tomography (PET), and CSF or blood biomarkers including amyloid beta (Aβ), pathologic tau (p-tau), Aβ42/Aβ40 ratio, tau/p-tau ratio, and neurofilament light chain (NfL). Plasma biomarkers are also being evaluated in clinical trials as exploratory endpoints and offer promise as minimally invasive, cost-effective tools for diagnosing AD, predicting cognitive decline, and determining trial or treatment eligibility.3

    Multiple sclerosis

    Several proteins are under investigation as biomarkers of MS, ranging from autoantibodies to biomarkers reflecting immune system alteration, blood-brain barrier disruption, oxidative stress, axonal or neuronal damage, and gliosis.3 One example of an ongoing trial exploring MS biomarkers involves assessment of single nucleotide polymorphism (SNP) haplotype, human leukocyte antigen (HLA) haplotype, and gene and protein expression in relation to clinical and MRI phenotype at baseline, as well as to change in disability, relapse rate, treatment response, and MRI measures of disease over a three-year period. The results of this study are expected to provide insight into disease pathogenesis and heterogeneity and to identify predictive biomarkers correlated with response to different therapies.4

    Parkinson’s disease

    As of January 2023, over 350 studies listed on ClinicalTrials.gov involve evaluation of biomarkers for PD.5 While clinical and imaging biomarkers have been the mainstay of diagnosis, an increasing number of biochemical and genetic biomarkers have emerged as potential tools for identifying at-risk populations, predicting prognosis, and discovering and delivering personalized therapeutic strategies. Still, no fully validated biomarker is currently available.

    Other CNS conditions

    Other active areas of biomarker investigation include Huntington’s disease, CNS germ cell tumors, traumatic brain injury, epilepsy, stroke, and major depressive disorder.3

    Digital biomarkers

    Digital biomarkers—collected via devices, wearables, functional assessments, mobile apps, and electronic patient reported outcomes (ePROs)—offer the opportunity for continuous data collection and monitoring outside of the healthcare setting. These biomarkers can support symptoms measures such as gait, balance, tremor, activity, sleep, cognition, and speech, which could be translated into clinical endpoints. For example, in multiple sclerosis, the current gold standard for performance assessment is the Timed 25 Foot Walk Test (T25FW). Collecting real-world data on walking speed via a wearable could be the digital equivalent of the T25FW.

    Incorporating biomarkers into CNS clinical trials

    There are several potential applications for biomarkers in CNS studies:

    • As prognostic biomarkers, to inform the likely outcome of the disease and the probability of benefit with additional therapy
    • As pharmacodynamic biomarkers, to assess the ability of the investigational therapeutic to engage its target
    • As predictive biomarkers, to serve as proof-of-concept surrogates, such as surrogates for drug activity

    The use of biomarkers may enable earlier go/no go decisions, provide reassurance that compounds are having the intended on-target effect at tolerable doses, assist in dose selection, and serve as inclusion/exclusion criteria. However, the incorporation of biomarkers also increases complexity in terms of protocol design, patient enrollment, study support requirements, and data analysis. It may also require development and validation of sensitive, reliable, and robust assays, which takes time.

    Conclusion

    Identification and validation of novel biomarkers for CNS disorders holds promise for addressing existing shortcomings in diagnosis and disease monitoring, as well as the discovery and development of new targets and therapeutics. Technological advances have increased the pace of biomarker discovery but while thousands of biomarkers have been identified, most are yet to be validated. Incorporation of biomarkers into clinical trials and, ultimately, clinical practice will help to improve study efficiency success and inform advancements in personalized neurology.

    Explore Precision's approach to therapeutic development in CNS >

    References

    1. Suhara T, et al. Strategies for utilizing neuroimaging biomarkers in CNS drug discovery and development: CINP/JSNP Working Group report. Int J Neuropsychopharmacol. 2017;20(4):285-294.

    2. Jain KK. Biomarkers in neurology, updated May 30, 2021. Available at https://www.medlink.com/articles/biomarkers-in-neurology.

    3. Cullen NC, et al. Plasma biomarkers of Alzheimer’s disease improve prediction of cognitive decline in cognitively unimpaired elderly populations. Nature Communications. 2021;12:3555.

    4. National Institute of Neurological Disorders and Stroke. Biomarkers in multiple sclerosis. Available at https://www.ninds.nih.gov/health-information/clinical-trials/biomarkers-multiple-sclerosis.

    5. ClinicalTrials.gov, searched January 24, 2023.


    • Tracey Owens

      Tracey Owens is a Director of Project and Clinical Trial Management at Precision, having 28 years of experience in managing Phase I-IV clinical trials. Tracey is highly experienced in providing directional oversight on rare disease, CNS, psychiatric and oncology clinical trials. Her experience notably includes: ALS, bipolar disorder, epilepsy, major depressive disorder, schizophrenia, idiopathic hypersomnia, CIDP, traumatic brain injury, multiple myeloma and dementia (including Alzheimer’s and Parkinson’s Disease.)

    • Vincent Shortino

      Vincent Shortino is a Sr. Clinical Trial Manager, bringing more than 20 years of experience to Precision. His experience spans all major therapeutic areas with a heavy emphasis on Cardiovascular and Rare Indications, across Phases I–IV. He brings solid perspectives inclusive of sites, pharma and CROs from his previous roles of Study Coordinator, Site Director, CRA, and Clinical Trial Manager.

    Precision for Medicine is part of the Precision Medicine Group, an integrated team of experts that extends Precision for Medicine’s therapeutic development capabilities beyond approval and into launch strategies, marketing communication, and payer insights. As one company, the Precision Medicine Group helps pharmaceutical and life-sciences clients conquer product development and commercialization challenges in a rapidly evolving environment.

    Visit the website
    Clinical Trial Services
    • Overview
    • Global Clinical Trial Support
    • Clinical Trial Management
    • Clinical Development Strategy
    • Clinical Trial Design
    • Biostatistics
    • Clinical Sample Management
    • Clinical Research Organization
    Specialty Lab Services
    • Overview
    • Immune Monitoring
    • Flow Cytometry
    • Genomics
    • Tissue & Liquid Biopsy
    • Bioanalytical Testing
    • Cytokine Analysis
    • Biospecimens
    • Sample Processing
    • Global Specimen Transport & Biostorage
    • Contract Research Organization
    • Bioanalysis
    • Neutralizing Antibody (NAb) Assays
    • PBMC Processing
    Data Sciences
    • Overview
    • Biostatistics
    • Clinical Data Management
    • Biometrics
    • QuartzBio
    • Virtual Sample Inventory Management
    Therapeutic Expertise
    • Overview
    • Preclinical Development
    • Early Phase Trials (I-IIa)
    • Late Phase Trials (IIb-III)
    • Oncology and Immuno-Oncology
    • Rare & Orphan Disease
    • Cell & Gene Therapy
    • Neurology
    • COVID-19
    • Autoimmune & Allergy
    • Pediatric
    • Companion Diagnostics
    About Us
    • Our Passion
    • Meet Our People
    • Careers
    • ESG Policy
    • Regulatory Information

    News & Insights
    • Publications
    • Case Studies
    • Thought Leadership
    • News
    • Events
    © 2023 Precision Medicine Group, LLC. All rights reserved. Privacy Policy    GDPR