Despite CNS drugs having seen high attrition rates in recent years, the field of neuroscience is experiencing a substantial renaissance. An improved understanding of CNS disease biology, the discovery of novel drug targets and the application of state-of-the-art technologies, are bringing much needed investment back into this blockbuster therapeutic area. Yet there remains much more to be done in terms of developing reliable preclinical models, validating CNS targets and biomarkers, and bridging the translation gap from preclinical discovery to the clinic. Join us for Cambridge Healthtech Institute’s Inaugural CNS Models and Translational Strategies conference, where promising preclinical models will be explored and evaluated, where future steps towards more accurate and reliable preclinical trials will be taken.

Final Agenda

Recommended All Access Package:

27 November: Single-Cell Analysis

27 November Dinner Course: SC1: Immunology Basics for Drug Discovery, Part 1: Immune System Overview

28-29 November: Optimizing Leads and Predicting Drug Toxicity

29-30 November: CNS Models and Translational Strategies

29 November Dinner Course: SC4: Immunology Basics for Drug Discovery, Part 2: Immune-Oncology and Autoimmunity

Thursday 29 November

12:30 Registration



13:25 Welcome Remarks

Joel Hornby, BSc, Conference Director, Cambridge Healthtech Institute

13:30 Chairperson’s Opening Remarks

William Z. Potter, MD, PhD, Senior Advisor, National Institute of Mental Health, National Institutes of Health (NIH)

13:35 Principles for Delivering Breakthrough Drug Discovery for CNS Disorders

Stuart W. Hughes, PhD, Director and Head of Pharmacology, Biological Sciences, Vertex Pharmaceuticals

CNS drug discovery presents a set of unique challenges that renders this therapeutic area a particularly tough nut to crack. Whether it be identifying novel validated targets that are grounded in robust human biology, clearly defining the translational value of specific animal models or creating appropriate biomarkers that enable effective development of clinical molecules, delivering success has proven far from easy. In this talk, I will discuss a set of key principles that address all of these pivotal issues.

14:05 Testing the Diseased Brain on the Chip: From Gene Expression to Functional Phenotyping of Patient-Derived Neuronal Cultures

Dirk_Schubert_2018Dirk Schubert, PhD, Assistant Professor, Group Leader “Cellular Neurophysiology”, Cognitive Neuroscience Department, Donders Institute for Brian, Cognition & Behaviour, Radboud University Medical Clinic Nijmegen

Human induced pluripotent stem cell derived neurons (iNeurons) from control lines as well as from patients can be used to unravel the mechanisms that underlie impaired network function and synaptic communication in patients with neurodevelopmental disorders, such as intellectual disability. Studying neuronal network formation and maturation by investigating molecular, structural and functional parameters revealed robust disease phenotypes that offer the platform for testing pharmacological interventions.


14:35 Characterization of Human Pluripotent Stem Cell derived Neural Progenitor Cells

Agota-ApatiÁgota Apáti, PhD, Senior scientist, Leader of Human Pluripotent Stem Cell Laboratory, Institute of Enzymolgy, Research Center for Natural Sciences- Hungarian Academy of Sciences

Human pluripotent stem cells (hPSC) offer a new perspective to overcome the limitation of existing models. In the present study neural progenitor cells (NPCs), which are committed to produce PROX-1-positive granule cells, were generated from hPSCs. Studying morphology, growth and differentiation capacity, neurite outgrowth and calcium signaling suggested that NPCs differentiated from hPSCs provide a reliable in vitro model system suitable for studying special aspects of neural development and regeneration.

14:50 Pathway Sensor-Based Functional Genomics Screening Identifies Modulators of Neuronal Activity

Alexander Herholt, PhD student, Ludwig-Maximilians University Munich

Despite the wealth of functional genomics screens for proliferation and toxicity using RNA interference (RNAi) or CRISPR/Cas9, neuronal signaling has been difficult to address so far. To overcome this limitation, we developed a novel pooled screening assay which combines barcoded activity reporters with pooled genetic perturbation in a dual-expression adeno-associated virus (AAV) library. With this we aim at pathway dissection and target identification in patient-derived cellular models of neuropsychiatric diseases.

15:05 Interactive Breakout Discussion Groups - View Details

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

Dish, Animal or Patient: How Can We Best Understand Neurodegenerative Disease?

Moderator: Stuart W. Hughes, PhD, Director and Head of Pharmacology, Biological Sciences, Vertex Pharmaceuticals

  • Is failure in neurodegenerative diseases related to a focus on inappropriate models?
  • Can neurodegeneration truly be modeled in vitro?
  • Should we pursue the biology of causation or progression?
  • What does a ‘validate target’ mean when it comes to neurodegenerative diseases?

Should a Robust Translational Path from Animals to Humans be Required to Advance a Compound?

Moderator: William Z. PotterMD, PhD, Senior Advisor, National Institute of Mental Health, National Institutes of Health (NIH)

  • Should a biomarker of drug effect in human brain always be required  to advance a novel compound into efficacy studies
  • Does there need to be preclinical data with a homologous biomarkers (e.g. fMRI for both animals and humans)?
  • If not, what constitutes adequate evidence that some brain effect observed in animals is occurring in humans?
  • Given clinical need are there arguments to advance compounds with some biomarker of acute effect?

16:05 Refreshment Break in the Exhibit Hall with Poster Viewing


16:45 Testing Drugs That Modulate Mitochondrial Biogenesis and Function in iPSC Models of Neurodegenerative Diseases

Michela_DeleidiMichela Deleidi, PhD, Helmholtz Young Investigator Group Leader, DZNE

While mitochondrial dysfunction is emerging as key in neurodegenerative diseases, a central question remains whether mitochondria are actual disease drivers and boosting mitochondrial biogenesis and function ameliorates pathology. We outline how patient-derived induced pluripotent stem cells and genome editing can be used for modelling mitochondrial demise occurring in neurodegenerative conditions such as Parkinson’s and Alzheimer’s disease. We outline progress in screening for compounds that improve energy metabolism and ameliorate neurodegenerative phenotypes.

17:15 Exploiting Human Stem Cells to Recapitulate Pathological Signatures of Human Brain Microenvironment

Catarina_BritoCatarina Brito, PhD, Lab Head, Advanced Cell Models Lab – Animal Cell Technology Unit, iBET & ITQB-NOVA

We have been exploiting platforms based on spheroid culture in perfusion stirred tank bioreactors for generation of functional neurospheroids - 3D structures containing neurons, astrocytes and oligodendrocytes, derived from human induced pluripotent stem cells. Recent data on the characterization of the cell microenvironment generated within neurospheroids will be presented. The application of neurospheroids as in vitro models to address molecular defects associated with neurological disorders that affect neural microenvironment homeostasis and as potency assays for drug testing will also be discussed.

17:45 Metabolic Profiling of Human Neural Cells for Disclosing Metabolic Determinants and Cell-Cell Interactions

Simão_DanielDaniel Simão, PhD, Senior Research Associate, Animal Cell Technology Unit, Instituto de Biologia Experimental e Tecnologica (iBET)

Metabolism plays an important role on cell fate, generating input signals that affect cellular dynamics at multiple levels. Different applications of metabolic characterization tools for neural stem cell-derivatives will be presented, encompassing the interrogation of toxicants’ effects on neuron-astrocyte interactions and determination of cell identity metabolic features. Overall, such strategies contribute for the identification of key metabolites in different cell types, which can have an impact for the design of targeted approaches for stem cell bioprocessing.

18:15 Close of Day and Dinner Short Course Registration

19:0021:30 Recommended Dinner Short Course*

SC4: Immunology Basics for Drug Discovery, Part 2: Immune-Oncology and Autoimmunity

* Separate registration required.

Friday 30 November

8:30 Registration and Morning Coffee


8:55 Chairperson’s Remarks

Stuart W. Hughes, PhD, Director and Head of Pharmacology, Biological Sciences, Vertex Pharmaceuticals

9:00 Nonclinical Models Supporting Orphan Drug Designations in Rare Neurodegenerative Conditions

dinah_duarteDinah Duarte, PhD, Assistant Professor, Lisbon University; Senior Assessor, INFARMED; PT Member, Committee for Orphan Medicinal Products, European Medicines Agency (EMA)

Many disease-specific animal models have been used to test emergent medicines in neurology. There is a body of evidence, however, that there is a substantial difficulty in choosing/accessing an optimal model or choosing measurements which would be truly informative of the product’s efficacy. We intend to present a critical revision of preclinical models that may be used to support orphan drug designations in rare neurodegenerative conditions, which are validated for each condition and to evaluate assays pertinent to the core features of selected conditions or otherwise relevant from the clinical standpoint.

9:30 Reports Given by Moderators from Thursday Afternoon Breakout Discussions

Stuart W. Hughes, PhD, Director and Head of Pharmacology, Biological Sciences, Vertex Pharmaceuticals

William Z. Potter, MD, PhD, Senior Advisor, National Institute of Mental Health, National Institutes of Health (NIH)

10:00 Coffee Break in the Exhibit Hall. Last chance for poster viewing.


10:45 Translating Neuroscience into Treatments: De-Risking through Partnerships

Bill_PotterWilliam Z. Potter, MD, PhD, Senior Advisor, National Institute of Mental Health, National Institutes of Health (NIH)

Translating the findings of neuroscience since the 1980’s into novel treatments for brain disorders has proven much more challenging than anticipated. The definitive methods required to be sure that one is validating or rejecting hypotheses on the potential of novel molecular interventions are sparse and unlikely to be developed within any single entity with the notable exception of PET ligands for orthosteric antagonists. The field is therefore exploring multiple public/private partnerships to develop and share the tools for ruling in or out the utility of novel intervention. A still-to-be-implemented possibility would be a true pre-competitive effort to de-risk a particular mechanism through a shared validation effort followed by some means of distributing the commercial rewards of finding the best molecule to affect the validated target.

11:15 From Gut-Brain Explorations to Effective Innovative Therapies in Parkinson Disease

Patrice_GARNIERPatrice Garnier, PhD, CEO, Amabiotics

Due to millions of years of coevolution, complex metabolic interactions exist between human and its gut microbiota. Not surprisingly, the number of reports associating dysbiosis and systemic diseases increased drastically over the past years. Amabiotics is a biopharmaceutical company that develops innovative diagnostics and microbiome-derived medicines to cure neurodegenerative diseases. Its lead compound, AMA-101 is targeted against Parkinson’s disease.

11:45 Human Pluripotent Stem Cells in ASD Discovery

Ravi Jagasia, PhD, Research Scientist, CNS, Hoffmann-La Roche, Roche Innovation Center Basel

The study of neurodevelopmental diseases, including autism spectrum disorders (ASD), and the development of effective treatments have been limited by a lack of appropriate models. Rodent models cannot model the complexity of the human genome and brain development in physiology and disease. To this end, human induced pluripotent stem cells (iPSC) represent a potentially limitless supply of patient-specific cells for the study of ASD.

12:15 Enjoy Lunch on Your Own


13:40 Chairperson’s Remarks

Stuart W. Hughes, PhD, Director and Head of Pharmacology, Biological Sciences, Vertex Pharmaceuticals

13:45 Dissecting Pathologic Molecular Signatures in Neurodegenerative Diseases through Chemical Chaperomics – From Mechanisms to Diagnostics and Treatment

Gabriela_ChiosisGabriela Chiosis, PhD, Professor, Member, Attending, Chemical Biology and Medicine, Memorial Sloan Kettering Cancer Center

I aim to discuss chemical chaperomics, a functional proteomics platform applicable for systematic proteomewide investigations of molecular alterations in Alzheimer’s disease and other neurodegenerative diseases. The method provides large-scale unbiased information on global protein-protein interactions and pathologic protein function changes in response to genetic and environmental factors. Implementation of this method to the analysis of patient-derived specimens may provide important information that is unavailable through, but complementary, to other ‘omics’ methods.

14:15 Antibodies for Brain Disorders Using the Brain Shuttle Blood-Brain Barrier Transport Technology

Per-Ola_FreskgårdPer-Ola Freskgård, PhD, Vice Director & Expert Scientist, Neuroscience, Roche Pharma Research & Early Development

This talk will briefly describe the status of the brain delivery field of biologics to the brain by highlighting recent advancements. In particular, the Brain Shuttle technology will be described, which is designed to be engineered into a standard therapeutic antibody and other types of biologics for successful BBB transport. Efficiency and safety aspects will be addressed illustrated with recent experimental data.

14:45 Progress in Neuroengineering for Brain Repair: From in vitro to in vivo Studies and Beyond

Michela_ChiappaloneMichela Chiappalone, PhD, Researcher (Team Leader), Rehab Technologies, Italian Institute of Technology (IIT)

In recent years, biomedical devices have been developed to target different neurological disorders. To reach useful therapeutic results, these tools need a multidisciplinary approach and a continuous dialogue between neuroscience and engineering, a field named Neuroengineering. In this talk, I will highlight the importance of developing novel neurotechnologies for brain repair (exploiting both in vitro and in vivo animal models) and present the major challenges expected for the next years.

15:15 Extended Q&A on Novel CNS Strategies

15:45 Close of Conference