Neuroscience and CNS drug development is experiencing a renaissance. A greater understanding of CNS related disease biology and the emergence of new, improved targets and technologies is bringing renewed interest, excitement and investment into this fascinating and potentially transformative area of medicine.

Cambridge Healthtech Institute’s Translational Strategies in CNS conference focuses on one of the key issues of CNS drug development – early stage development. Key session topics include developing and validating CNS targets and biomarkers, bridging the preclinical/clinical translation gap, evaluating the strengths and weaknesses of current preclinical models, challenging “gold-standards”, understanding mechanism of action, dose selection, neuroimaging, neuroinflammation, neuroimmunology, and more. 2018’s meeting will focus on progress being made in the field of CNS drug development rather than historical reflection.

Final Agenda

Wednesday, June 20

11:00 am Registration Open (America Foyer)

11:50 Bridging Luncheon Presentation: Nuclear Imaging of Neuroinflammation in Rodent Models of Neurodegenerative Diseases

Tuulia_HuhtalaTuulia Huhtala, PhD, Head, Biomarkers and in vitro Biology, Discovery, Charles River

Activation of the mitochondrial translocator protein (TSPO) is linked to neuroinflammation, and TSPO ligands can be used for in vivo PET or SPECT imaging. In the current studies, we utilized these ligands to assess the extent of neuroinflammation after lipopolysaccharide (LPS) infusion, following induction of multiple sclerosis (MS) and neuropathic pain.

12:20 pm Dessert and Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)

Essex South

2:30 Refreshment Break in the Exhibit Hall with Poster Viewing (America Ballroom)

St. George CD

3:10 Chairperson’s Opening Remarks

Murali Gopalakrishnan, PhD, MBA, Senior Director, Head, Search & Evaluation Neuroscience, AbbVie

3:15 KEYNOTE PRESENTATION: What Does Recent Clinical Data Tell Us about the Amyloid Cascade Hypothesis?

Eric_KarranEric Karran, PhD, Vice President, Foundational Neuroscience Center, AbbVie Neuroscience, AbbVie

The amyloid cascade hypothesis (AH) has been the predominant view of Alzheimer’s disease pathogenesis. The AH in particular has informed many of the pharmacological approaches that have been tested in Phase III clinical trials, none of which has demonstrated efficacy. Given this disappointing outcome, the validity of the AH has been questioned, and this presentation will review the status of both clinical research and the AH.

3:45 Identification of Plasma Biomarkers and Therapeutic Targets for Prevention of Alzheimer’s Disease

Takaomi_SaidoTakaomi Saido, PhD, Senior Team Leader, Proteolytic Neuroscience, Riken Brian Science Institute

For prevention of Alzheimer’s disease (AD), it is necessary to diagnose preclinical AD by plasma biomarkers and to stop the progression of A pathology. Application of single App knock-in mice (Saito et al., Nat Neurosci, 2014) has enabled us to identify candidates for the biomarker and therapeutic targets. Validation of these targets will be described.

4:15 Three Essential Elements for Assessing Potential Neurotoxicity in Preparation for Submissions to FDA

Baun JimJim Baun, Vice President, Scientific Operations, NeuroScience Associates, Inc.

The ultimate endpoint of neurotoxicity is neuronal death. Detection of neurotoxicity depends on three key elements: 1) survival time after insult, 2) adequate sampling of the tissue, and 3) sensitivity of detection method. Survival time- disintegrative debris does not persist indefinitely. Sampling- the brain has over 600 populations of neurons. Detection of neuronal death- the stain to be used must be general to reveal the event regardless of cell death mechanism.

4:45 Targeting Glial Cell Pathology in Huntington’s Disease with an Antibody to Semaphorin 4D

Elizabeth_EvansElizabeth Evans, PhD, Vice President, Preclinical Research, Vaccinex, Inc.

Semaphorin 4D mediates glial cell activities including reactive gliosis and the survival of oligodendrocyte precursor cells that repair and remyelinate brain lesions. Preclinical target validation and development of PD biomarkers for VX15, a humanized anti-SEMA4D antibody, will be discussed. Preliminary brain imaging data from an ongoing Phase I/II clinical trial supports the hypothesis that SEMA4D antibody blockade preserves brain volume and restores metabolic activity in pre- and early-manifest HD.

5:15 Neurochemical Imaging: Connecting Basic Neuroscience to the Human Experience

Jacob_HookerJacob M. Hooker, PhD, Phyllis and Jerome Lyle Rappaport MGH Research Scholar, Associate Professor of Radiology, Harvard Medical School

Positron emission tomography (PET) provides a window into the human brain to study chemistry provided that a radiotracer can be developed to measure molecular interactions. This presentation will describe the incredible opportunities in PET imaging and the tools that the Hooker Lab has co-developed to better realize its full potential.

5:45 Close of Day and Dinner Short Course Registration*

*Separate registration required.

Thursday, June 21

7:30 am Registration Open (America Foyer) and Morning Coffee (Foyer)

St. George CD

8:00 Chairperson’s Remarks

Dario Doller, PhD, Senior Director, Exploratory Science, SAGE Therapeutics

8:05 Preclinical Development of a Translatable Biomarker Assay for Proteopathic Amyloid Seeds

Kimberly McDowellKimberly McDowell, PhD, Research Scientist, Preclinical Research, Proclara Biosciences, Inc.

8:35 Thinking beyond the Well-Known Biomarkers for Patient Selection and Monitoring in Alzheimer’s Disease Clinical Trials

Viswanath_DevanarayanViswanath Devanarayan, PhD, Adjunt Professor, University of Illinois, Chicago

A major challenge with AD drug development is the variability of patient response due to the heterogeneity of disease progression. In recent years, diagnostics based on CSF Amyloid beta and Tau proteins (Shaw et al, 2009) or Brain Hippocampal Volume from MRI have been used to select and monitor patients in clinical trials. Our analyses of the CSF proteomics data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) has revealed more predictive diagnostics tools. In particular, we have identified a novel CSF peptide that when combined with the CSF Amyloid Beta, Tau and brain hippocampal volume, results in a 2-fold improvement in the prediction of AD progression in an independent group of MCI subjects. Such alternative tools for patient selection, monitoring and potentially as surrogate endpoints are needed for developing viable disease modifying treatments for AD.


Renishawk  9:05 Optimising Intraparenchymal Convection Enhanced Delivery 

Max_WoolleyMax Woolley, PhD, BEng (Hons), BEng, Neuro Applications, Renishaw plc

Translating Convection Enhanced Delivery device knowledge from laboratories to clinical practices is stifled by critical factors; poor distribution drug/device incompatibility and device design. Presenting a novel device’s performance through pre-clinical case study results, illustrating a de-risk, evidenced approach to fast-track new CED therapies towards successful neuro-oncology and neuro-degenerative clinical trials.

 9:35 Find Your Table and Meet Your Moderator

9:40 Interactive Breakout Discussion Groups

This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas and active networking.

Lost in translation? Asking the Right Questions in the Right Language

Dario Doller, PhD., Sage Therapeutics

  • CNS disease etiology understanding: Who owns it?
  • What are the major disconnects between lab experimentation and clinical research?
  • Are differences in physiology between preclinical species and human affecting the translational gap?
  • Patient segmentation: Strategies and outcomes
  • Correlation or causation? Importance of genetic links for different CNS diseases
  • What are the attributes that have real impact minimizing risk during novel target selection?
  • Human as a model for human – What is the future of experimental medicine in CNS drug discovery?

Improving the Success Rate of CNS Therapies

Takaomi C. Saido, PhD, Laboratory Head, Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute

  • Why have more than 400 medication candidates for Alzheimer’s Disease failed?
  • Which therapies have the best chance to succeed, and why?
  • Immunotherapy for neurodegenerative disease
  • What is the future of immunotherapy?

10:20 Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)

11:05 A New Paradigm for Therapeutic Discovery in Psychiatry

Gopi_ShankerGopi Shanker, PhD, Head of Psychiatry, Neuroscience Department, Novartis Institutes for Biomedical Research (NIBR)

Recent advances in the genetics of psychiatric disorders have led to a renewed focus on development of effective therapies in this area. However, the lack of predictive animal models continues to be a challenge for drug discovery. New advances in biomarker development through case-control as well as longitudinal studies in patients are paving the way for the development of new translational strategies and discoveries in psychiatry.

11:35 A Quantitative Pharmacology Model of Neuroactive Steroid Efficacy in Movement Disorder

David Nguyen, PhD, Principal Scientist, SAGE Therapeutics

SAGE-217 is a novel GABA-potentiator which is currently in clinical development for mood and motor related disorders. This presentation will discuss the clinical characterization of SAGE-217 from a PK/PD modeling perspective, comparing endpoints measured in Phase I related to efficacy, target engagement, and adverse events.

12:05 pm Digital Technologies for CNS Translational Studies

Brandon_Farley_2Brandon Farley, PhD, Senior Scientist, SAGE Therapeutics

Wearable devices can complement clinical assessments by providing continuous monitoring of movement parameters and other physiological signals, both inside and outside of the clinic. We present data from Parkinson’s disease and essential tremor clinical trials which validate device-measured tremor against clinical tremor scales, and which demonstrate that devices are sensitive to pharmacological modulation of tremor. The rich pharmacodynamic datasets enabled by wearables are being employed in the development of Sage-217 and other GABAa receptor modulators for movement disorders.


12:35 Networking Luncheon in the Exhibit Hall with Poster Viewing (America Ballroom)

St. George CD

1:55 Chairperson’s Remarks

Dario Doller, PhD, Senior Director, Exploratory Science, SAGE Therapeutics

2:00 An Updated View for Translating Mechanisms Underlying Alzheimer’s Disease into Effective Therapeutics

Martin_ZhangCan (Martin) Zhang, MD, PhD., Assistant Professor of Neurology, Harvard Medical School, Genetics and Aging Research Unit, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital

2:30 The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases

Charlotte_MadoreCharlotte Madore, PhD, PostDoc Research Fellow, Harvard Medical School, Associate Scientist, Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital

Microglia play a pivotal role in the maintenance of brain homeostasis but lose homeostatic function during neurodegenerative disorders. In recent studies, TREM2 (triggering receptor expressed on myeloid cells 2) induced APOE signaling, and targeting the TREM2-APOE pathway restored the homeostatic signature of microglia in ALS and AD mouse models and prevented neuronal loss in an acute model of neurodegeneration. This presentation will discuss the latest work in this area.

3:00 Neuroinflammation in Huntington's Disease: New Insights with 11C-PBR28 PET/MRI

Cristina_GomezCristina Lois Gomez, PhD., Research Fellow, Gordon Center for Medical Imaging, MGH, Harvard Medical School

To improve our understanding of neuroinflammation in Huntington's disease, we measured translocator protein (TSPO) expression using 11C-PBR28 and simultaneous PET/MRI. Standardized-uptake-value ratios, normalized by whole brain uptake, were calculated for data acquired 60-90 min after radiotracer administration. We identified distinct patterns of regional neuroinflammation (as defined by TSPO overexpression relative to a control group) in the basal ganglia of Huntington's disease patients. These patterns were observed at the individual level in all patients, with region of interest analysis confirming significant differences between patients and the control group in the putamen and the pallidum.

3:30 Immunodementia: Human Genetics-guided Translational Research in Alzheimer's Disease 

Akihiko_KoyamaAkihiko Koyama, PhD., Executive Director, Global Head of Translational Science, Neuroscience Business Group

4:00 Close of Conference

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