Capturing the Effects of COMT Inhibition on Sequelae of Brain Injuries with NIHTB and TBI-QoL

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1 Capturing the Effects of COMT Inhibition on Sequelae of Brain Injuries with NIHTB and TBI-QoL Emily Adams Berich, B.S. Research Coordinator, Sheppard Pratt-Lieber Research Institute

2 SPL Mission: Develop clinically relevant point-of-care studies, bringing together interdisciplinary teams of clinicians and scientists and utilizing cutting-edge methods from the neurosciences, genetics data science and emerging technologies.

3 SPL Multidisciplinary, Point-Of-Care Clinical Research

4 SPL Largest non-for-profit provider of mental health services in the United States Translational Research Institute at Johns Hopkins School of Medicine Focus: genetics, stem cell biology, data science & drug discovery BASIC SCIENCES DRUG DRUG DISCOVERY GENETICS

5 BACKGROUND Traumatic brain injury a significant cause of morbidity and mortality leading cause of long-term disability in children and adults under million per year in USA There are no FDAapproved medications to treat the sequelae of TBI. neuropsych psychiatric apathy depression disinhibition executive function PTSD dysprosody psychosis neurological/ medical seizures headaches motor/sensory endocrine

6 BACKGROUND tolcapone potent COMT-inhibitor Blood-brain barrier permeable (1:100) FDA approved for Parkinson s disease adjunct treatment Found to improve prefrontal cortical function in healthy controls evidence for possible clinical utility in FDT, gambling, depression Can a FDA-approved COMT inhibitor known to improve dopaminergic tone and shown to increase PFC dependent cognitive tasks be effective in treating patients with brain injuries?

7 METHODS 2 step clinical study

8 METHODS clinical study: step 1 Tolcapone 200 mgtid Consent Interview PRO Battery start TBI-QoL Day 0 Day 1 Day 14 PRO Measures Physical Exam Biosample collection Neurocognitive Assessments Neurocognitive Battery start NIHTB Neurocognitive Assessments PRO Measures Biosample Collection 60 mins 120 mins FrSBe STAI GDS PROMIS 60 mins 120 mins TMT MWCST HVLT BVMT CIFA PCT BTA DS

9 RECRUITMENT Clinic Population Point-of-care research within a tertiary referal clinic. -Approx. 400 patients with BI -359 have been screened Gender TBI Presentation Eligibility Male Female Mild 49% Severe 45% 6% Moderate Not Eligible Eligible Consented Completed

10 RESULTS Current Sample, 22 subjects completed Avg years since injury: 15 SD:14.6 years Minimum: 2 years ago Maximum: 56 years ago 7 female, 15 male Mean age: 49.9 yo (SD 13.4), Min age 27 yo, Max age 69 yo BI Severity 9 13 Severe Mild Self- Injury Fall 1 2 Assault BI Cause Accident MVA Tolcapone Tolerability Other Dizziness Fatigue 7 15 Headache Diarrhea Insomnia Appetite Change Nausea

11 CNNS Cognitive Tests NIH TB Cognition RESULTS Neurocognitive Assessments, baseline

12 RESULTS Neurocognitive Assessments, pre-post NIH TB Cognition CNNS Cognitive Tests Fluid Composite Pattern Comparison 7.3 <0.001*** * Flanker * List Sorting * DCCS * Picture Sequence * PCT Total * BTA Total BVMT Total HVLT Total Digit Span TMT A TMT B mwcst Total mwcst Errors Perseverativ CIFA-d * Acceptable CIFA-d % Unacceptabl CIFA-v Total CIFA-v Letter CIFA-v *

13 TBI-QoL RESULTS PRO Assessments, baseline

14 RESULTS PRO Assessments, baseline TBIQol & POMS/STAI TBIQol & FrSBe/GDS

15 RESULTS PRO Assessments, pre-post TBI-QoL Comprehension 4.6 <0.001* General Cognition 5.5 ** <0.001* Executive Function ** Dyscontrol ** Anger Self Evaluation Grief/Loss * Resilience Anxiety Depression Well-being Headache Pain Pain Interference * Fatigue * Upper Extremity Mobility

16 CONCLUSION Conclusions

17 Thank you! Alexander Maclay, BS SPL Electronic Data Coordinator Elizabeth Postell, BS Former SPL Research Coordinator Andrew Jaffe, PhD Lead Investigator - Data Science, LIBD Daniel Weinberger, MD - CEO, LIBD Vassilis Koliatsos, MD Director, SPHS Neuropsychiatry Clinic Margo Lauterbach, MD Director, SPHS Concussion Clinic Robert Schloesser, MD Executive Director, SPL Contact Emily Adams Berich, B.S. Research Coordinator, SPL eberich@sheppardpratt.org