Cambridge Healthtech Institute’s 3rd Annual

CNS Targets and Translational Strategies

Advancing CNS Drug Development

June 18-19 2019

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 transformative area of medicine.

Cambridge Healthtech Institute’s CNS Targets and Translational Strategies conference focuses on the key issues of CNS drug development – including CNS target discovery and validation, 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. 2019’s meeting will focus on progress being made in the field of CNS drug development rather than historical reflection.

Final Agenda

Tuesday, June 18

7:00 am Registration Open and Morning Coffee

Cityview 1

8:00 Chairperson’s Remarks

Dario Doller, PhD., Drug Research Consulting, Alcyoneus/ScienceWorks


8:10 KEYNOTE PRESENTATION: Increasing the Odds of Success in CNS Drug Development: New Horizons

Sarwar_NadeemNadeem Sarwar, Founder & President, Eisai Center for Genetics Guided Dementia Discovery (G2D2), Eisai Inc.

8:40 KEYNOTE PRESENTATION: Translational Opportunities for Brain Proteinopathies, Alzheimer’s Disease and Parkinson’s Disease, through Pathophysiology-Based Imaging and Biofluid Biomarkers

Lutman_JohanJohan Luthman, PhD, EVP,  Research and Development, Lundbeck

Amyloid pathophysiology-based PET imaging and CSF biofluid biomarkers are now used routinely in major clinical Alzheimer’s disease trials for eligibility screening when studying amyloid-directed therapeutics. Moreover, quantitative amyloid PET imaging is providing important possibilities to conduct clinical proof of principle trials for anti- amyloid investigational therapeutics. Tau PET imaging and CSF tau markers are now emerging as a similar tool for patient identification as well as PoP in studies on tau-directed therapeutics.

9:10 KEYNOTE PRESENTATION: Lysosomal Dysfunction in Parkinson’s Disease: From Genetics to the Clinic

Sardi_PabloPablo Sardi, PharmD, PhD, R&D Director, Sanofi

This presentation will discuss: clinical, genetic and experimental evidence underlies the relevance of lysosomal dysfunction in Parkinson’s disease (PD); mutations in the lysosomal glucocerebrosidase gene (GBA) accelerate PD progression; First trial has begun testing a GBA pathway modulator in a genetically defined population, and Modulation of the lysosomal pathway may also benefit a larger sporadic patient population.

9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing


10:25 Featured Presentation: Targeting KCC2 for Epilepsy and Other Brain Disorders

Ross A. Cardarelli, PhD., Lead Scientist, AstraZeneca-Tufts University Laboratory for Basic and Translational Neuroscience, Tufts University

Deficits in GABAergic inhibition result in the abnormal neuronal activation and synchronization that underlies seizures. However, the molecular mechanisms responsible for transforming a normal brain into an epileptic one remain largely unknown. Here we discuss the growing evidence that 2K+-Cl- cotransporter (KCC2) dysfunction has a central role in the development and severity of the epilepsies.

10:55 Behavior & Biomarker Characterization of the SOD1G93A Model of ALS Following Chronic Dosing with a Brain Penetrant HDAC6 Inhibitor Compound

Niroomand_ShahriarShahriar Niroomand, PhD, Associate Principal Scientist, Neuroscience, Merck Research Laboratories

Our three month in vivo study aimed to investigate whether pharmacological inhibition of the -Tubulin deacetylase HDAC6 would be sufficient to preserve axonal transport and attenuate disease phenotypes in the ALS SOD1G93A mice as demonstrated in vitro using ALS patient iPSC neurons and in vivo after HDAC6 genetic ablation. We designed a novel brain penetrant HDAC6i compound to achieve sustained target engagement in the CNS, followed by repeated assessment of motor function using rotarod and CMAP with concomitant measurement of disease progression biomarker pNfH. Our results indicate that sustained inhibition of HDAC6 in the SOD1G93A mice from a post wean pre-symptomatic age did not delay onset or slow the progression of motor dysfunction as they aged. This suggests that SOD1G93A may not be a suitable model to test the modulation of axonal transport in ALS, reinforcing the need for additional pre-clinical models for such a heterogenous disease.

11:25 Zebrafish Models for Early Research and Development in Neurodegenerative and Neuromuscular Diseases

Arantza Muriana, Co-Founder & CEO, Biobide USA

Zebrafish presents numerous advantageous that make it a powerful animal model in neuroscience research. During this presentation we will review several neurodegenerative and neuromuscular rare disease zebrafish models (ALS, Duchnne, Dravet Syndrome), their application in CNS drug screening, target validation and other early research and development activities.

11:55 Transition to Lunch

12:00 pm Enjoy Lunch on Your Own

12:30 Session Break


1:05 Chairperson’s Remarks

Dario Doller, PhD., Drug Research Consulting, Alcyoneus/ScienceWorks

1:10 Targeting Nucleocytoplasmic Transport in Amyotrophic Lateral Sclerosis and Dementia

Freyermuth_FernandeFernande Freyermuth, PhD, Massachusetts General Hospital, Mass General Institute for Neurodegenerative Diseases

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons leading to fatal paralysis. Mutations in the FUS gene are responsible for familial cases of ALS, and cytoplasmic mislocalization of the protein is a pathological hallmark in a form of frontotemporal dementia. We determined that FUS mutations lead to defects in the nuclear membrane integrity that can be restored by targeting FUS nuclear cytoplasmic transport.

1:40 The TSC Preclinical Consortium: De-Risking Drug Discovery and Repurposing for Tuberous Sclerosis Complex

Roberds_StevenSteven Roberds, PhD, CSO, Tuberous Sclerosis Alliance

The TSC Preclinical Consortium is a public-private partnership catalyzing development of new treatments for tuberous sclerosis complex. The TS Alliance holds licenses to use specific mouse models at CROs, including rights to test compounds for commercial entities. This has attracted nine pharmaceutical companies to join the consortium, testing 15 proprietary drug candidates. Fifteen additional compounds have been tested by the TS Alliance, with data shared to all consortium members.

2:10 Beyond iPSC Based Disease Models: A Translatable Drug Discovery Platform for Status Epilepticus

Haag_DanielDaniel Haag, CSO and Co-Founder, NeuCyte

Using direct reprogramming of iPSCs to generate defined human neural tissue, NeuCyte developed cell-based assays with complex neuronal structure and function readouts for versatile pre-clinical applications. Focusing on electrophysiological measurements, we demonstrate the capability of this approach to identify adverse neuroactive effects, evaluate compound efficacy, and serve phenotypic drug discovery.

2:25 Refreshment Break in the Exhibit Hall with Poster Viewing

2:30-2:45 Speed Networking: Young Professionals


3:10 New Targets and Biology in Neuroimmunology

Hasson_SamSamuel Hasson, PhD, Senior Scientist, Neuroscience, Amgen

Information coming from human genetic studies has implicated several key pathways in the pathogenesis of Alzheimer’s disease (AD). These include processing of the Amyloid Precursor Protein and activation of the innate immune response. Here we describe efforts to understand the biology of targets in each of these pathways in order to help translate that into potential, disease-modifying therapeutics for the treatment of AD.

3:40 Microglial Immune Checkpoint in Neurodegeneration and Brain Tumors

Joseph El Khoury, MD, Associate Professor of Medicine, Harvard Medical School

Similar to lymphocytes, microglia, the innate immune cells of the CNS, have several immunological checkpoints that prevent their overreaction to external stimuli. These checkpoints are different from those of lymphocytes. They include Trem2, Cx3cr1/fractalkine and progranulin that keep the inflammatory response in check. Dysregulation of any of these checkpoints occurs in neurodegeneration and affects the response to brain tumors. As with T cell immune checkpoints, microglial immune checkpoints may be important targets for therapy.

4:10 Transition to Keynote


5:20 Taste of New England Welcome Reception in the Exhibit Hall with Poster Viewing

5:25 Meet the Plenary Keynotes

6:25 Find Your Table, Meet Your Moderator

6:30 Breakout Discussion Groups 

7:30 Close of Day

Wednesday, June 19

7:00 am Registration Open and Morning Coffee

Cityview 1

8:00 Chairperson’s Remarks

Dario Doller, PhD., Drug Research Consulting, Alcyoneus/ScienceWorks

8:05 Harnessing the Gut-Brain Axis to Discover Novel CNS Therapeutics

Donabedian_DavidDavid H. Donabedian, PhD, Co-Founder & CEO, Axial Biotherapeutics

In ASD, a human commensal bacterial therapy has shown to correct gut permeability, restore a healthy microbial composition and ameliorate core and non-core behavioral symptoms associated with ASD. In addition, Axial has developed a gut-selective, nonbacterial-based therapy that has shown to improve barrier integrity and ameliorate core and non-core behavioral symptoms associated with ASD. The findings suggest that targeting the gut microbiome may provide a new approach for diagnosing and treating PD and ASD.

8:35 Preclinical Translational Strategies for the Neuroinflammatory Aspects of Neurodegenerative Disease

Levenson_JonathanJonathan Levenson, PhD, Vice President, Translational Biology, Tiaki Therapeutics

Chronic neuroinflammation is a hallmark of Alzheimer’s disease and other neurodegenerative disorders. Tiaki Therapeutics has developed a novel ex vivo platform that faithfully models the neuroinflammatory signature observed in patients afflicted with a neurodegenerative disease. Tiaki has focused on the role of neuroinflammation in Alzheimer’s disease, specifically microglial dysfunction. Tiaki has identified druggable, molecular targets on microglia that when modulated mitigate neuroinflammation and improve neuronal health.

Quanterix 9:05  Utilization of Blood Biomarkers in Neurodegenerative Disease Research

Warner_GregGreg Warner, PhD, Senior Field Applications Scientist, Quanterix Corporation

We will describe the use of Simoa technology to measure neurogenerative disease-associated proteins in serum and plasma and their relation to traditional measurements in CSF.  We will also discuss how these biomarker measurements can be combined with traditional monitoring methods such as PET and MRI in patient response to therapeutic regimens.

9:35 Coffee Break in the Exhibit Hall with Poster Viewing

10:05 Poster Winner Announced


10:20 The Development and Application of New PET Neuroimaging Probes

Wang_ChaningChangning Wang, PhD., Assistant Professor of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School

Molecular imaging, such as PET, has been widely used in medical research and drug discovery. We have developed new imaging tools and applied them in clinical research and drug discovery. In this presentation, I will discuss the development and application of molecular neuroimaging techniques for brain research. In the past few years, we have developed the first generation of epigenetic PET probes for HDACs an bromodomains. The first probe for class I HDAC imaging has successfully advanced to human imaging studies and shows promising results so far. With these tools, we know the epigenetic changes in patients for the first time, and we also developed a series of new epigenetic inhibitor. Our work is a unique example on the multidisciplinary research, including molecular imaging, medicinal chemistry, clinical research and preclinical drug discovery

10:50 Novel Markers that Significantly Enhance the Prediction of Alzheimer's Disease Progression

Devanarayan_ViswanathViswanath Devanarayan, PhD, Adjunct Professor, University of Illinois, Chicago

The 2018 NIA-AA research framework proposes a ATN classification system with beta-Amyloid deposition (A), pathologic Tau (T), and neurodegeneration (N) for the diagnosis and staging of Alzheimer’s Disease (AD). We use proteomics data from the AD neuroimaging initiative to develop simple cut-point based signatures that reinforces this ATN research framework. When applied to a separate MCI group at baseline, subjects satisfying these signature criteria experience over two-fold faster progression to AD compared to signatures based on the ATN research framework.

11:20 Translational Potential of Neuropeptide Derived “stapled” Peptides in Metabolic and Neurological Disorders

Marwari_SubhiSubhi Marwari, PhD, Postdoctoral Fellow, Department of Psychiatry, SUNY Upstate Medical University

The blood-brain barrier poses a significant challenge to drug development efforts for central nervous system disorders. Introducing an innovative “hydrocarbon-stapling” approach and combining with intranasal delivery technology in neuropeptides, relaxin-3 and NPY, we have demonstrated the potential of the neuropeptide-receptor system in pursuit of the most effective translational pharmacological strategy to reversing depression, anxiety, and related metabolic disorders.

11:50 Transition to Lunch

12:00 pm Enjoy Lunch on Your Own

12:30 Transition to Plenary


2:20 Booth Crawl and Dessert Break in the Exhibit Hall with Poster Viewing

2:25 Meet the Plenary Keynotes

3:05 Close of Conference

Stay on to attend Wednesday, June 19 - Thursday, June 20

Blood-Brain Barrier