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Society for Neuroscience Annual Meeting Show Preview: Taking notice of the neurological
48th Annual Meeting
November 3-7, 2018
San Diego Convention Center
San Diego, Calif.
Taking notice of the neurological
SfN annual meeting gets ready for networking, the most recent neurological research and the newest neuroscience
In a year of news about Alzheimer’s disease drugs stalling and controversy over amyloid vs. tau as a root cause, along with other new research like high levels of the herpes virus being found in the brains of people with Alzheimer’s disease (according to a study in the journal Neuron), you have to admit that 2018 has been full of neurological notifications—and that’s just for one disease. So attending a show like the 48th annual meeting of the Society for Neuroscience (SfN)—also known as Neuroscience 2018—can be critical in order to stay on top of the most current information about neurology and neurological diseases.
SfN’s annual conference will be making its way back to San Diego this year (after hitting Washington, D.C., last year) to enjoy the West Coast sun and, as the organization notes of the non-weather-related aspect of attending, “Whether you will be presenting a poster or networking with prospective employers, SfN’s annual meeting can provide you with an unparalleled opportunity to learn, connect and advance in your career.”
SfN’s annual meeting regularly attracts more than 30,000 attendees representing around 80 countries, including more than 500 exhibiting companies and almost 300 journalists. This year, SfN expects nearly 14,000 abstracts with new research, lectures by world-renowned scientists from around the world and symposia discussing exciting advances in neuroscience, as well as events for networkers, advocates and other career seekers.
“Neuroscience 2018 will feature lectures, symposia and events for scientists at all career stages,” notes SfN. “Sessions and events at the annual meeting are designed to provide attendees with a range of opportunities, including scientific enrichment, career development and professional networking.”
New for 2018
SfN has added a new programming feature to the Neuroscience 2018 meeting. Its Dual Perspectives session is intended to serve as a platform where annual meeting attendees can learn about the history and the various arguments, research and viewpoints surrounding a particular hot topic. The 2018 presenters, Vikaas Sohal and Jessica Cardin, will deliver their respective views on gamma oscillations. The discussion, “Gamma—Fumes or Fundamental,” will be moderated by Matthew Shapiro of SfN’s Program Committee.
Gamma (γ) oscillations (~20–100 Hz) are associated with sensory processing, cognition, memory and attention. There is general agreement that γ oscillations represent potentially useful markers of local circuit dynamics, but also major debate about whether the oscillations themselves contribute to brain function. Sohal and Cardin will argue for different sides of this debate. Do oscillations enhance specific functions of cortical circuits, or do they mainly provide insight into ongoing synaptic interactions among cells?
Not truly new this year, but still fresh, are some things introduced in 2016, like the Storytelling Minisymposium, which invites a panel of speakers to tell inspiring stories about their personal experiences, the impact of such experiences have had on their career in neuroscience and how to communicate stories within and beyond the scientific community. This year’s offering is “Telling Stories of Science,” chaired by Dr. Wendy A. Suzuki of New York University.
Also introduced in 2016, the Basic-Translational-Clinical Roundtables integrate basic, translational and clinical aspects of a disease of disorder with particular emphasis on new developments, controversies or updates. Sessions are designed to stimulate debate and to engage the audience. With the addition of a fourth roundtable, the 2018 sessions will focus on neuropsychiatry, neurological disorders, neurodegeneration and patient perspectives of neuroprosthetic devices.
The usual (but valuable) fare
One of the main attractions for Neuroscience 2018 will be the Featured and Special Lectures, covering a broad variety of neuroscience and neurology topics. The Albert and Ellen Grass Lecture will be “Neural Sequences in Memory and Cognition,” presented by Dr. David W. Tank of Princeton University. SfN says of the lecture, “The BRAIN Initiative is transforming neuroscience through improved methods for large-scale neural recording at cellular resolution. The application of these methods during working memory, decision-making and navigation tasks has repeatedly demonstrated sequences of activity across the recorded neural population that tile the behavior. New analysis and modeling efforts are providing clues as to the functional roles and mechanisms of this widely observed form of neural circuit dynamics.”
The David Kopf Lecture on Neuroethics, titled “When Is an Adolescent an Adult?—Implications for Justice Policy” and presented by Dr. B. J. Casey of Yale University, will explore advances in brain imaging techniques and the insights they provide into why adolescents experience and respond to the world in the unique ways in which they do. “These developmental findings have influenced a series of Supreme Court decisions on the treatment of adolescents,” mentions SfN. “Now, emerging evidence of developmental changes in the brains of young adults (ages 18 to 21) suggest that they, too, may be immature in ways that are relevant to justice policy.”
In the Dialogues Between Neuroscience and Society lecture, musician and composer Pat Metheny will be presenting “Music and the Brain.” As SfN explains, “Music is a universal language and a powerful force in the world. It can have incredible impact on our brain and easily make us cry or make us joyful. Just a few notes of a song can cause us to remember memories long past. Pat Metheny is a legendary jazz guitarist who understands the power of music. He has received three gold albums and 20 Grammy Awards. In this dialogue, Mr. Metheny will discuss, with a panel of SfN members, the impact of music on the brain and on our emotions and memory, as well as the process of creativity in music, art and science and the role of music in healing.”
The History Of Neuroscience Lecture, “Deciphering Neural Circuits: From the Neuron Doctrine to the Connectome,” will be presented by Dr. Marina Bentivoglio of the University of Verona. The lecture covers the evolving understanding of neuronal connectivity and how it is key to the progression of neuroscience. “The enunciation in 1891 of the Neuron Doctrine led to the explosion of neuroscience in the 20th century; since the beginning of the 21st century, connectomics has introduced novel concepts, igniting hopes to crack the code of the human brain,” says SfN. “Traversing the itinerary of paradigm shifts in the understanding of neural circuits, this lecture will highlight current challenges and foci of research.”
The Peter and Patricia Gruber Lecture will be done a little differently this year—its theme is Decision, Reward, and the Basal Ganglia, but the lecture will be split between three presenters: Drs. Ann M. Graybiel, Okihide Hikosaka and Wolfram Schultz. Graybiel of the McGovern Institute for Brain Research at the Massachusetts Institute of Technology will present “The Striatum and Decision-Making Based on Value,” Hikosaka of the National Eye Institute is the speaker for “Parallel Basal Ganglia Circuits for Cooperative and Competitive Decision-Making” and Schultz of the University of Cambridge will present “About Reward.”
Special and featured lectures
“Each year, SfN’s Program Committee invites leading scientists to give lectures on hot topics in neuroscience,” SfN notes. “The Presidential Special Lecture Series is developed by SfN's president with the lectures stemming from his or her area of interest.”
Neuroscience 2018 plans to offer four Presidential Special Lectures: “From Nanoscale Dynamic Organization to Plasticity of Excitatory Synapses and Learning” by Dr. Daniel Choquet of the University of Bordeaux; “From Salvia Divinorum to LSD: Toward a Molecular Understanding of Psychoactive Drug Actions” by Dr. Bryan L. Roth of the University of North Carolina at Chapel Hill; “Neurobiology of Social Behavior Circuits” by Dr. Catherine Dulac of Harvard University and the Howard Hughes Medical Institute; and “The dArc Matter of Synaptic Communication” by Dr. Vivian Budnik of the University of Massachusetts Medical School.
Several featured lectures are also organized under nine themes that characterize the educational program: Theme A is Development; Theme B is Neural Excitability, Synapses, and Glia; Theme C is Neurodegenerative Disorders and Injury; Theme D is Sensory Systems; Theme E is Motor Systems; Theme F is Integrative Physiology and Behavior; Theme G is Motivation and Emotion; Theme H is Cognition; and Theme I is Techniques.
“Genetic Specification of Neuronal Identity” by Dr. Oliver Hobert of Columbia University is the sole lecture to fall under Theme A.
Theme B holds two lectures, “Biochemical Computation in Postsynaptic Compartments: Implications for Synaptic Plasticity, Learning, and Memory” by Dr. Ryohei Yasuda of the Max Planck Florida Institute for Neuroscience, and “Neuronal Diversity Within the Ventral Tegmental Area and Co-Release of Neurotransmitters” by Dr. Marisela Morales from the National Institute on Drug Abuse, NIH.
“Clinical Neuroscience Lecture: From Axon Regeneration to Functional Recovery After CNS Injury” by Dr. Zhigang He of Boston Children's Hospital and “Understanding Regeneration of Complex Body Parts” by Dr. Elly M. Tanaka of the Research Institute of Molecular Pathology are the lecture pair from Theme C.
Theme D boasts a triple feature: “A Genetic Roadmap to Understanding Auditory Perception Mechanisms” by Dr. Christine Petit of Institut Pasteur Collège de France; “Light Detection in the Eye: The Big Picture” by Dr. King-Wai Yau of Johns Hopkins University School of Medicine; and “Sensorimotor Circuits for Social Communication” by Dr. Mala Murthy of Princeton University.
Themes E, F and G each have one featured lecture, which are, respectively, “Bidirectional Interactions Between the Brain and Implantable Computers” by Dr. Eberhard E. Fetz of the University of Washington; “The Genetics, Neurobiology, and Evolution of Natural Behavior” by Dr. Hopi E. Hoekstra of Harvard University/HHMI; and “Reward Processing by the Dorsal Raphe” by Dr. Minmin Luo of the National Institute of Biological Sciences, Beijing.
“Neural Dynamics of the Primate Attention Network” by Dr. Sabine Kastner of Princeton University and “New Computational Perspectives on Serotonin Function” by Dr. Zachary F. Mainen of Champalimaud Institute, Portugal make up the lectures for Theme H.
And Theme I includes “Neural Data Science: Accelerating the Experiment-Analysis-Theory Cycle in Large-Scale Neuroscience” by Dr. Liam Paninski of Columbia University and “Organelle Structure and Dynamics: What High-Resolution Imaging Is Uncovering” by Dr. Jennifer Lippincott-Schwartz of Janelia Research Campus.
For more information on the meeting not included in this section, visit SfN’s website at www.sfn.org.
Symposia at Neuroscience 2018
Theme A: Development
Theme B: Neural Excitability, Synapses, and Glia
Theme C: Neurodegenerative Disorders and Injury
Theme D: Sensory Systems
Theme E: Motor Systems
Theme F: Integrative Physiology and Behavior
Theme H: Cognition
Theme I: Techniques
Professional Development Workshops
These workshops at the SfN annual meeting are categorized by tracks to help attendees identify which will be of the greatest benefit to them. This year’s tracks are Career Paths, Collaboration & Networking, Success in Academia and Neuroscience Education.
Saturday, November 3
Sunday, November 4
Monday, November 5
Sunday, November 4
What We Know, What We Don't Know: How Can We Better Understand Alzheimer’s Disease to Develop Effective Treatments?
Dr. David M. Holtzman
Recent genetic data suggest a key role for glia in influencing Alzheimer’s disease (AD). AD pathology can now be detected by assessing biomarkers in living people, and many promising treatments are in development. This session will review an update of the main molecules that play a role in AD and discuss the current understanding of AD, new diagnostic methods and treatments.
Monday, November 5
Molecular Therapies for Neurological Diseases
Dr. Frank Bennett
This roundtable will highlight spinal muscular atrophy (SMA) as an example of the progress being made in translating knowledge of the molecular basis of a disease to therapies that transform how the disease is managed. Topics to be discussed include SMA background, antisense, gene therapy and small molecule approaches to treat SMA. In addition, lessons learned from these development programs will be discussed, highlighting how they translate to other neurological diseases.
Rapid Antidepressant Action: Synaptic Mechanisms and Clinical Aspects
Dr. Ege T. Kavalali
This panel will focus on how ketamine, a glutamate receptor antagonist, produces rapid and sustained antidepressant responses in patients. Deep brain stimulation has also shown promise for depression treatment. The mechanisms underlying rapid antidepressant responses provide novel perspectives into mood disorders and their treatment. The panel will discuss these novel treatments and the mechanisms underlying their action.
Tuesday, November 6
Neuroprosthetic Devices: A Patient’s Perspective on Brain Computer Interfaces
Dr. Florian Solzbacher
Patients will talk about their physical limitations and why they participated in time-intensive research for scientific knowledge. They will cover the challenges, breakthroughs and difficult decisions that come with wearing a neuroprosthetic device. They will also speak to the benefits, despite trial-and-error methodologies and invasive surgeries, of participating in brain-computer interface (BCI) research, how it has changed their lives and where they believe researchers should push the future of BCI technologies.
Future Annual Meetings
2019 Chicago, Oct. 19 - 23
2020 Washington, D.C., Oct. 24 - 28
2021 Chicago, Nov. 13 - 17
2022 San Diego, CA Nov. 12 - 16
NEUROLOGY NEWS ROUNDUP IN HONOR OF NEUROLOGY 2018:
Genervon presents GM6 mechanisms of actions in Alzheimer’s disease
PASADENA, Calif.—Following the closure of several research programs for Alzheimer’s disease in early 2018, the FDA issued a release entitled “Draft Guidance for Industry: Early Alzheimer’s Disease: Developing Drugs for Treatment.” Encouraged by the proposed changes in the new guidance, Genervon’s research team reported new findings that its drug candidate GM6 attenuates Alzheimer’s disease (AD) in an early AD transgenic APP mice model.
Application of GM6 over a four-month period in young APP/ΔPS1 double-transgenic mice resulted in attenuation in Aβ peptide levels, reduction of inflammation and amyloid load, increased cathepsin B expression and improved spatial orientation. In addition, treatment with GM6 increased brain nerve growth factor levels and tempered memory impairment by approximately 50 percent at the highest dose.
In the AD mouse models, inflammation seemed to play a key role in the disease process, and GM6 reduced cytokines (TNF-α, IL-1β, TGFβ, etc.) and inflammatory mediators (CD-68 and GFAP), which can contribute to pathogenesis, and modulated cathepsin B and cleavage of APP to Aβ. These findings suggest that GM6 may modulate disease-determining pathways at an early stage to slow the histological and clinical progression of AD. The results were presented on Sept. 25 at the New York Academy of Science Symposium “Neuroimmunology—The Impact of Immune Function on Alzheimer’s Disease” and are available at https://www.genervon.com/animal-models-data.
The anti-inflammation effect of GM6 is one of several mechanisms of actions that GM6 modulates in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and AD. Other mechanisms include increased neurogenesis, decreased oxidative stress and apoptosis, increased extracellular matrix stability, increased cell adhesion, increased synaptic transmission, decreased Aβ toxicity and the differential expression of disease-associated genes. Genervon’s research team recently summarized the mechanisms of action of GM6 for both ALS and AD; summaries are available on Genervon’s website (https://www.genervon.com/mechanisms-of-action/).
More generally, GM6 has been shown to have very good drug properties, according to the company. GM6 was previously tested in a Phase 2A ALS study, which confirmed the drug’s safety in humans with no serious drug-related, treatment-emergent adverse effects. In that trial, Genervon observed favorable trends in GM6-treated patients, including a slowed decline in forced vital capacity and ALS Functional Rating Scale, along with decreased plasma abundance of ALS biomarkers (e.g., TDP-43, Tau and SOD1). These results strongly suggest that GM6 has neurogenesis and anti-inflammatory effects in various neurodegenerative diseases, such as ALS and AD, with common underlying pathways.
Monitoring cognitive decline for trials
WATERTOWN, Mass.—BioSensics has received a grant award from the National Institutes of Health (NIH) to develop technology for continuous, remote monitoring of cognitive decline. This technology will reportedly enable the objective assessment of instrumental activities of daily living, life space and also digital social interactions, which are biomarkers of many diseases and disorders, from Alzheimer’s disease and dementia to depression. With the addition of this new technology, BioSensics seeks to expand the capabilities of its Sensor-Integrated Digital Platform for clinical trials to include tools for objective measurement of cognitive and mental health.
Dr. Joseph Gwin, vice president of research and development at BioSensics, announced the NIH grant award on Sept. 25 during his presentation at the DPharm: Disruptive Innovations to Advance Clinical Trials conference in Boston, where Gwin discussed the critical role that wearable sensors can play in clinical trials.
“BioSensics offers a wide range of solutions and services to measure movement- and mobility-related endpoints in clinical trials. We are thrilled to have the support of the NIH to further expand our offerings to measure endpoints that are directly relevant to a wide range of mental and cognitive disorders,” said Gwin.
The three-year project will be conducted in collaboration with Baylor College of Medicine. The solution, which consists of a wearable movement sensor, GPS and software for measuring digital social interactions, will have impacts in both clinical trials and clinical practice.
“Technology can play a key role in promoting healthy and independent aging. The ability to continuously monitor cognitive health plays a key role in managing care and support for the elderly population,” said Dr. Bijan Najafi, professor in the Michael E. DeBakey Department of Surgery at Baylor College of Medicine, who is the principal investigator of the new grant award.
In May 2018, BioSensics announced the launch of its Sensor-Integrated Digital Platform for clinical trials. This platform was also developed in part with funding from the NIH and is currently being used in clinical trials for a variety of indications, including neurodegenerative diseases, stroke and cognitive disorders.
“We have been very pleased with the favorable reception of our platform by the pharmaceutical industry and look forward to steady growth of our clinical trials division,” said Gwin.
Allergan announces acceptance of sNDA for Vraylar
DUBLIN—Allergan Inc. announced at the end of September that the U.S. Food and Drug Administration (FDA) has accepted for review the company’s supplemental New Drug Application (sNDA) for Vraylar (cariprazine), seeking to expand the indication to include the treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults in the current product label.
The sNDA is supported by data from three pivotal trials, including RGH-MD-53, RGH-MD-54 and RGH-MD-56. In all three studies, cariprazine demonstrated greater improvement than placebo for the change from baseline to week six on the Montgomery Asberg Depression Rating scale (MADRS) total score. Both cariprazine 1.5 mg and 3 mg demonstrated superiority to placebo in reducing depressive symptoms associated with bipolar I depression.
“Despite decades of development, bipolar depression remains difficult to treat. Importantly, bipolar I patients will need treatment for the full spectrum of of their disorder,” said Dr. Gary Sachs, associate clinical professor of psychiatry at Harvard Medical School. “If approved for bipolar depression, cariprazine would be the first and only partial agonist with proven efficacy for both the manic and depressive symptoms of bipolar I disorder. That is very encouraging news for patients, their families and the psychiatry community.”
The efficacy and safety of cariprazine in bipolar depression was evaluated in several randomized, placebo-controlled studies—one exploratory Phase 2 study (RGH-MD-52) in bipolar I and II patients, and three pivotal studies (RGH-MD-56, 53 and 54) in bipolar I patients.
RGH MD 52 was a Phase 2 multicenter randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study comparing cariprazine to placebo in outpatients with a primary diagnosis of bipolar I or II disorder who were experiencing a major depressive episode. The study randomized 233 patients with bipolar I and bipolar II disorder to one of three dose groups for eight weeks of double-blind treatment: cariprazine 0.25 mg to 0.75 mg; cariprazine 1.5 mg to 3 mg; or placebo.
RGH-MD-56 was a Phase 2b randomized, double-blind, placebo-controlled, parallel-group clinical trial in adult patients with bipolar I depression. A total of 584 patients were randomized to evaluate the efficacy, safety and tolerability of cariprazine 0.75 mg, 1.5 mg and 3 mg compared to placebo in the treatment of outpatients with bipolar I depression. Patients underwent a no-drug screening period of approximately seven to 14 days, followed by eight weeks of double-blind treatment (primary endpoint was six weeks) and a one-week, no investigational product safety follow-up period.
RGH-MD-53 and RGH-MD-54 were identical Phase 3 randomized, double-blind, placebo-controlled, parallel-group, multicenter, fixed-dose clinical trials in adult patients with bipolar I depression. Patients were randomized in both studies aiming to evaluate the efficacy, safety and tolerability of cariprazine 1.5 mg and 3 mg compared to placebo in outpatients with bipolar I depression. Patients underwent a no-drug screening period of approximately seven to 14 days, followed by six weeks of double-blind treatment and a one-week, no investigational product safety follow-up period.
Cariprazine was generally well tolerated in the trials. The most commonly reported adverse events were nausea, akathisia, restlessness and upper respiratory tract infection. Adverse events led to discontinuation in 6.7 percent of cariprazine-treated patients versus 4.8 percent of placebo treated patients.
“This sNDA filing provides an important step towards the availability of a potential treatment option for the approximately five million patients suffering with bipolar I depression. These positive pivotal studies, demonstrated the efficacy and safety of Vraylar for the treatment of bipolar depression,” said David Nicholson, chief research and development officer at Allergan. “Vraylar is the flagship product of our psychiatry portfolio and demonstrates Allergan’s commitment to the mental health community.”
Cariprazine was approved by the U.S. Food and Drug Administration in September 2015, and is marketed as Vraylar in the United States for the treatment of schizophrenia in adults and acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.
First-in-human dosing of CVN424 for Parkinson’s disease
BOSTON—Recently, Cerevance announced the start of dosing in a Phase 1 first-in-human clinical trial of CVN424, an oral compound being developed for symptomatic treatment of Parkinson’s disease. This first-in-class compound modulates a novel protein target selectively expressed in an important class of dopamine-responsive neurons in the striatum. The double-blind, single- and multiple-ascending dose study being conducted in the United States will assess the safety, tolerability and pharmacokinetic profile of CVN424 in healthy subjects, as well as effects of food on the compound’s absorption.
“CVN424 activates key dopamine-responsive motor pathways but not the neurons implicated in levodopa-induced dyskinesias, the uncontrolled movements that afflict so many Parkinson’s patients,” noted David Margolin, senior vice president of clinical and translational medicine at Cerevance. “This selectivity may allow CVN424 to match the positive effects of the current standard of care, levodopa, without its side effects.”
CVN424 is an orally bioavailable, brain-penetrant small molecule. It reportedly acts as a potent inverse agonist of a novel target that is highly selectively expressed in striatal neurons of the dopamine D2 receptor dependent pathway (the “indirect” pathway), compared to the D1 receptor dependent (“direct”) pathway. The compound has improved locomotor activity in animal models of Parkinson’s disease.
“The completion of preclinical studies, the successful filing of the IND and now the initiation of the first-in-human clinical trial for CVN424 are significant milestones for our company,” said Dr. Mark Carlton, chief scientific officer of Cerevance. “This compound exemplifies Cerevance’s approach of identifying and modulating therapeutic targets that are selectively expressed in disrupted circuits or vulnerable neuronal and glial populations in central nervous system diseases.”