2023 Conference Agenda

Intrasynaptic Alterations as a Therapeutic Approach for Improved Function after Experimental Traumatic Brain Injury
This presentation aims to discuss the effect of experimental traumatic brain injury on key synaptic processes and protein machinery important for neurotransmission. This talk will highlight recent findings in identifying novel synaptic therapeutic targets and interventions to improve neurotransmission and promote functional recovery after brain injury.
Shaun Carlson, Ph.D., Research Assistant Professor, Department of Neurological Surgery and Clinical and Translational Science Institute (CTSI), University of Pittsburgh

Neural Stem Cell and Microbiome Transplant Therapies in a Pediatric Pig Traumatic Brain Injury Model
Neural stem cells (NSCs) are a potential therapeutic for pediatric traumatic brain injury (TBI) with the ability to differentiate and integrate into damage brain tissue and produce neuroprotective and regenerative factors to promote cell survival. Similarly, the transplant of a healthy gut microbiome has also been suggested as neuroprotective therapy that can decrease brain injury and improve recovery in TBI. Our research has recently demonstrated that NSCs and microbial transplantation are capable of limiting intracerebral tissue damage in a pediatric pig model leading to improved functional outcomes.
Franklin West, Ph.D., Professor of Regenerative Bioscience, University of Georgia

Results from a Prospective, Placebo-controlled, Double-blinded Randomized Trial Suggests Salovum Given as Antisecretory Factor Significantly Reduces 30-day Mortality in Adult Patients with Severe TBI:
In this presentation Dr. Cederberg will for the first time, present results from a prospective, placebo-controlled, double-blinded, randomised phase 2-trial evaluating the effect of antisecretory factor, given as a food supplement (Salovum), on 30-day mortality, Intracranial pressure (ICP )and Treatment Intensity level (TIL). 100 adult patients with severe TBI was included in the trial. He will also detail the story behind Salovum and antisecretory factor and its proposed mechanisms.
David Cederberg, MD, Senior Consultant of Neurosurgery, Head of Neurointensive Care Unit, Skane University Hospital (Lund, Sweden)

Traumatic Brain Injuries are the Cause of Chronic Traumatic Encephalopathy: Evidence & Implications
For the past twenty years, the cause of CTE has been hotly debated. Establishing a cause will have significant consequences for sports and military organizations. This presentation will review the overwhelming evidence for repetitive head impacts and traumatic brain injuries as the cause of CTE, then explore what should happen next to prevent future cases of CTE and care for individuals and families impacted by the disease.
Christopher Nowinski, Ph.D., Chief Executive Officer, Concussion Legacy Foundation

(tentative title) Circuit-targeted Therapeutics for Emotional Dysregulation After Traumatic Brain Injury
Depression and anxiety are major causes of disability after TBI, and traditional psychiatric treatments are less effective for these patients. In this session, Dr. Siddiqi will present novel findings to demonstrate that TBI-associated emotional dysregulation is a unique clinical syndrome defined by a unique pattern of brain circuit abnormalities. These circuit abnormalities can be selectively modulated using transcranial magnetic stimulation, a widely available antidepressant treatment which has shown preliminary efficacy for TBI-associated depression.
Shan Siddiqi, MD, Assistant Professor of Psychiatry, Brigham & Women's Hospital

Psychedelics for Neurotrauma: A Review of Mechanisms and Future Outlooks
Recent in vitro, in vivo, and case report studies suggest that psychedelics could serve as a therapeutic capable of acting on several elements of the secondary brain injury, including neuroinflammation, cellular apoptosis, excitotoxicity, blood-brain-barrier disruption, and mitochondrial dysfunction, as well as potentiating endogenous neuroplasticity repair mechanisms. While touching on multiple psychedelics, I focus on the application of ayahuasca as a potential therapeutic and provide support for the hypothesis that it could improve cerebrovascular and blood brain barrier function, increase neuronal network efficiency, impart neuroprotective effects against oxidative and excitotoxic stress, and attenuate neuroinflammation. Moreover, I propose an experimental framework which emphasizes matching of mechanism of action with mechanism of pathophysiology by leveraging utile in vitro and in vivo models. Psychedelics as the future of TBI pharmacotherapies could allow clinicians to simultaneously address multiple facets of TBI neuropathology while treating common psychiatric comorbidities.
Victor Acero, Ph.D. Candidate, Department of Bioengineering, Chair, Penn Psychedelic Collaborative , University of Pennsylvania

Panel Session: The TBI Precision Research Roadmap
The TBI Precision Research Roadmap outlines the research projects & policies needed to accelerate a first generation of precision diagnostics and targeted treatments for TBI and also the systemic changes required to ensure that all those suffering from TBI can get access to these new innovations, and other support and care, they so desperately need. This session will include:
⇒ An introduction to TBI Roadmap and Action Alliance 
⇒ The TBI Roadmap - Lines of Effort & Advancing Diagnostics
⇒ Overview of BRAINCommons Platform and TBI Community Framework
⇒ Demo of BRAINCommons Platform
Moderator:
Magali Haas, MD, Ph.D., Chief Executive Officer & President, Cohen Veterans Bioscience
Panelists:
Ragini Verma, Ph.D., Head of Biomarkers & Clinical Development, Cohen Veterans Bioscience
Maryan Zirkle, MD, MS, MA, Executive Director, BRAINCommons
Stephen D. Larson, Ph.D., CEO & Co-Founder, MetaCell

Selectively Neutralizing Soluble TNF to Improve Pathophysiological and Functional Outcomes following TBI
This presentation will provide an overview of our recent data showing the efficacy of a novel biologic known as XPro1595 that selectively neutralizes the soluble form of TNF to improve hippocampal pathophysiological and associated functional outcomes following TBI, the underlying mechanisms of action, and a reduced risk of developing Alzheimer’s disease pathology.
Kirsty Dixon, Ph.D., Associate Professor, Surgery and Anatomy & Neurobiology , Virginia Commonwealth University

The Use of Synaquell in Subconcussive Head Injuries: a Randomized Placebo-control Study
Subconcussive head impacts can lead to short-term changes in brain function, and repetitive exposure is linked to later-life onset of neurodegenerative conditions. Objective assessment tools are critical to be able to measure subconcussive impairments, as well as to evaluate efficacy of any potential interventions to reducing the cumulative effects. This presentation will discuss a recent placebo-control study that used NeuroCatch to evaluate the effect of Synaquell, a non-pharmacological dietary supplement, on subconcussive changes in contact sport athletes.
Shaun Fickling, Ph.D., Lead R&D Scientist, NeuroCatch

DYRK1a Inhibition Reduced Tau Hyperphosphorylation, Neuroinflammation and Improved Locomotor Function, in a Mouse Model of Repeat Mild Traumatic Brain Injury
Chronic neuroinflammation and phosphorylated Tau (pTau) deposits are features of traumatic brain injury (TBI). Dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) phosphorylates Tau and regulates several immune response mediators. We explored DYRK1A inhibition as a potential treatment to limit the neurodegenerative consequences of repetitive mild TBI (r-mTBI) in a transgenic mouse model. The results from this study demonstrated that DYRK1A inhibition reduced chronic neuroinflammation, pTau accumulation and restored locomotor deficits related to r-mTBI in this context.
MIrta Grifman, Ph.D., VP Clinical Development & External Innovation, Biosplice Therapeutics

AST-004, a Potential Cerebroprotectant and TBI Treatment, Successfully Advances in Clinical Phase 1 First-In-Human Study
AST-004, a small molecule adenosine A3/A1 receptor agonist, has demonstrated broad cerebroprotective efficacy in mouse, pig and non-human primate models of TBI and stroke. A Phase 1 single ascending dose safety study was recently completed in 52 healthy normal volunteers. The preclinical and clinical data will be reviewed, as well as future directions and product formulations.
William Korinek, Ph.D., Co-founder & Chief Executive Officer, Astrocyte Pharmaceuticals

Novel Neuroprotective NMDA Receptor (NMDAR) Antagonists for Acute Traumatic Brain Injury (TBI)
Drug development for TBI has focused on the secondary injury cascade after TBI, including release of the excitatory and potentially neurotoxic glutamate neurotransmitter. Biomarker, microdialysis and clinical trials data suggest an acute treatment with an NMDAR antagonist may reduce excitatory damage and thereby improve or accelerate outcomes. However, NMDA antagonists’ properties may differ dramatically depending on site of binding, functional activity, off-rates, and overall potency. EuMentis Therapeutics is evaluating 4 compounds with promising in vitro and in vivo results to date using a well-accepted porcine model of TBI in order to select one for IND-enabling studies. Assays selected, compound properties and the porcine model of TBI (Kilbaugh lab, Hospital U Pennsylvania) will be presented and discussed.
Randall Marshall, MD, Chief Medical Officer, EuMentis Therapeutics