Mitochondrial Medicine 2019: Washington DC Mitochondria from the Bench to the Bedside

June 26-29, 2019 – Scientific/Clinical Sessions Hilton Alexandria Mark Center, Alexandria, VA

Day 1: June 26 (Wednesday) – Plaza A Morning Platform Session (1) – Platform Title: Opening and Organelle Cross-Talk and Mitochondrial Dynamics

8:00 Welcome and Opening Remarks Philip Yeske, PhD, UMDF Science and Alliance Officer Amel Karaa, MD, and Carla Koehler, PhD, Course Co-Chairs

Primary Mitochondrial Disease Patient Testimony – My Diagnostic Odyssey, What My Diagnosis Means to Me, and My Hopes for the Future – Stacy Taylor, mother of Marshall and Sam, both with genetically confirmed mitochondrial disease and Rachel Schanzenbach, an adult with mitochondrial disease

8:30 Keynote Address: Mitochondrial Genetic Medicine: Past, Present and Future Speaker: Douglas Wallace, PhD, Center for Mitochondrial and Epigenomic Medicine, Philadelphia, PA

9:15 Endoplasmic Reticulum (ER) and Mitochondria and the Role of Close Contacts between these Organelles in Lipid Trafficking Speaker: William Prinz, PhD, NIDDK, NIH Intramural Research Program, Bethesda, MD

9:45 The Mitochondria and Lysosome – Two Organelles with Important Roles in Aging and Metabolism Speaker: Adam Hughes, PhD, University of School of Medicine, Salt Lake City, UT

10:15 Break – Plaza Foyer

10:45 The Role of Mitochondrial Chaperones in Cellular Adaptation and Tumor Metabolism Speaker: Dario C. Altieri, MD, Wistar Institute Cancer Center, Philadelphia, PA

11:15 Abstracts (4)

12:15 Lightning Round Talks (10 x 1 min) – Non CME

12:30 Lunch – Plaza C (additional seating in Outdoor Garden)

Afternoon Platform Session (2) – Platform Title: Mitochondrial Architecture: Regulation and Maintenance

2:00 Epigenetic Control and Mitochondrial DNA Methylation Speaker: Takehiro Yasukawa, PhD, Department of Clinical Chemistry and Laboratory Medicine Graduate School of Medical Sciences, Kyushu University, Japan

2:30 In vivo imaging of mitochondrial membrane potential in non-small cell lung cancer Speaker: David Shackelford, PhD, University of California Los Angeles (UCLA), David Geffen School of Medicine, Los Angeles, CA

3:00 Mitochondria and Psychiatric Disorders Speaker: Ana C. Andreazza, Pharm PhD, Canada Research Chair, University of Toronto and Scientific Director, The Canada Mitochondrial Network, Canada

3:30 Break – Plaza Foyer

4:00 Iron-Sulfur Protein Biogenesis Disorders Speaker: David Lynch, MD, PhD, Children's Hospital of Philadelphia, Philadelphia, PA

Scientific/Clinical Program Schedule Page 2 of 4

REV 6/20/19

4:30 Abstract Presentations (3)

5:15 Lightning Round Talks (10 x 1 min) Non CME

5:30 Reception and Poster Sessions (Non CME) - Even Numbers Stay at Posters – Laurel/Arbors Rooms

7:30 Adjourn

A 5-minute question and answer period is included in each of the speaker's allotted time.

Day 2: June 27 (Thursday) – Plaza A Morning Platform Session (3) – Platform Title: Mitochondrial Communication and Quality Control

8:00 Mitochondria and Microbiota Inter-Talk Speaker: Keshav Singh, PhD, University of Alabama Birmingham, AL

8:30 Innate Immune Response and Inflammation Speaker: A. Phillip West, PhD, Texas A&M University Health Science Center, College Station, TX

9:00 Immunity and Mitochondrial Diseases Speaker: Peter McGuire, MS, MBBCh, Metabolism, Infection and Immunity Section, National Human Genome Research Institute, NIH, Bethesda, MD

9:30 Mitochondrial Phenocopies and Secondary Mitochondrial Dysfunction Speaker: Shamima Rahman, FRCP PhD, UCL Great Ormond Street Hospital of Child Health, London, UK

10:00 Break – Plaza Foyer

Morning Platform Session (4) – Platform Title: Leigh Syndrome – Mitochondrial Medicine Society (MMS) Session

10:30 Pluripotent Stem Cell Models for Study of Leigh Syndrome Speaker: Shilpa Iyer, PhD, University of Arkansas, Fayetteville, AR

10:45 Leigh Syndrome Registry Data Speaker: Mary Kay Koenig, MD, University of Texas McGovern Medical School, Houston, TX

11:00 Leigh Syndrome – The US experience: Data from the NAMDC Registry

Speaker: Austin Larson, MD, University of Colorado School of Medicine, Denver, CO

11:15 Leigh Syndrome – The United Kingdom (UK) Experience Speaker: Shamima Rahman, FRCP PhD, UCL Great Ormond Street Hospital of Child Health, London, UK

11:45 Leigh Syndrome – The Australian Experience Speaker: David Thorburn, PhD, Murdoch Children’s Research Institute, Australia

12:15 The UMDF Leigh Syndrome Roadmap Project Speaker: Bruce Cohen, MD, Akron Children’s Hospital, Akron, OH

12:45 MMS updates (Non CME)

1:00 Lunch – Plaza C (additional seating in Outdoor Garden)

Afternoon Platform Session (5) – Platform Title: Federal Updates on Research and Clinical Trials for Mitochondrial Disease

2:00 Food and Drug Administration (FDA) and Rare Disease Drug Approvals Speaker: Dragos Roman, MD, FDA-Center for Drug Evaluation and Research Rare Diseases, Silver Springs, MD

2:30 Abstract Presentations (3)

Scientific/Clinical Program Schedule Page 3 of 4

REV 6/20/19

3:15 Lightning Round Talks (10x1 min) Non CME

3:30 Break – Plaza Foyer

4:00 National Center for Advancing Translational Sciences (NCATS) and Mitochondrial Disease Research Speaker: Anne Pariser, MD, NIH/National Center for Advancing Translational Sciences (NCATS), Bethesda, MD

4:30 National Institutes of Health (NIH) Funding for Mitochondrial Disease Research Speaker: Danuta Krotoski, PhD, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD

5:00 Department of Defense (DOD) Funding for Mitochondrial Diseases Speaker: Kathryn Argue, PhD, Congressionally Directed Medical Research Programs (CDMRP), Ft Detrick, MD

5:30 Break & Poster Sessions (Non CME) - Odd Numbers Stay at Posters – Laurel/Arbors Rooms

A 5-minute question and answer period is included in each of the speaker's allotted time.

Day 3: June 28 (Friday) - 8:00-10:00 – Plaza C and 10:30-5:00 – Plaza A Morning Platform Session (6) – Platform Title: State of Mitochondrial Medicine (Scientific, Clinicians, Patients, Families, etc). Platform 6 updates are NOT part of the CME Activity.

8:00 Welcome: UMDF and the Mitochondrial Medicine Community (Non CME) Speaker: Brian Harman, UMDF President & CEO, Pittsburgh, PA

8:30 The Big Pitch: UMDF accelerators Research Grant Prize Finals – Brian Harman and Philip Yeske, PhD The accelerators Prize was established in 2019 with an aim to fund promising research from postdoctoral researchers. Come hear our finalists give their ‘fast’ pitch to be awarded the first annual accelerators Research Prize. (Non CME)

9:30 Externally-led Patient-Focused Drug Development and Science & Alliance Updates (Non CME) Speaker: Philip Yeske, PhD, UMDF Science & Alliance Officer, Pittsburgh, PA

10:00 Break – Plaza Foyer

10:30 North American Mitochondrial Disease Consortium (NAMDC) Updates (Non CME) Speaker: Michio Hirano, MD, Columbia University, New York, NY

10:45 Mitochondrial Care Network Update (Non CME) Speaker: MMS Leadership – Sumit Parikh, MD, The Cleveland Clinic, Cleveland, OH

11:00 Mitochondrial Disease Sequence Data Resource (MSeqDR) (Non CME) Speaker: Marni Falk, MD, Children’s Hospital of Philadelphia, Philadelphia, PA

11:15 Abstract Presentations (4)

12:15 Late Break Big Data - The Inheritance of Mitochondrial DNA Heteroplasmy is under Nuclear Genetic Control in Humans Speaker: Patrick Chinnery, MBBS, PhD, FRCP, FMedSci, University of Cambridge, Cambridge, UK

12:45 Lunch – Plaza C (additional seating in Outdoor Garden)

Afternoon Platform Session (7) – Platform Title: Harnessing the Big Data: Where Are We Now?

2:00 Mitochondrial DNA Deletions in POLG Disease Speaker: William Copeland, PhD, NIEHS, Research Triangle Park, NC

Scientific/Clinical Program Schedule Page 4 of 4

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2:30 Mechanisms of Mitochondrial Dysfunction in Patient Cells and Stem Cell-Derived Models Speaker: David Thorburn, PhD, Murdoch Children’s Research Institute, Australia

3:00 Break – Plaza Foyer

3:15 Integrated Cardiac Mitochondrial Phenome; Half-life of Mitochondrial Proteins, Emphasis on Cardiac Biology Speaker: Peipei Ping, PhD, University of California Los Angeles (UCLA), Los Angeles, CA

3:45 The Presentation of Mitochondria Disorders in the Newborn: Time for Whole (Mitochondrial and Nuclear) Genome Sequencing Speaker: David Dimmock, MD, Rady Children’s Institute for Genomic Medicine, San Diego, CA

4:15 UMDF Funded Projects and MMS/MRS Cash Award Presentations (NOTE – new presentation time for this year’s cash awards) – Philip Yeske, PhD, UMDF Science & Alliance Officer

A 5-minute question and answer period is included in each of the speaker's allotted time.

5:00 Adjourn

5:30 Reception and Cash Bar – Plaza Foyer

6:30 An Evening of Energy Banquet Celebration for Scientific/Clinical and all Patient/Family Attendees - music, accelerator vote, and Awards Ceremony – Plaza C

Day 4: June 29 (Saturday) – Plaza A (MSeqDR in Beech) Morning Platform Session (8) – Platform Title: Bench to Bedside in Mitochondrial Disease

7:15-7:45 Mitochondrial Disease Sequence Data Resource (MSeqDR) Workshop – Beech Room Speaker: Marni Falk, MD, and Lishuang Shen, PhD

8:00 Mitochondrial Disease and Oxygen: Can there be too much of a Good Thing? Speaker: Vamsi K. Mootha, MD, Harvard Medical School, Boston, MA

8:30 Mitochondrial Transfer – High Throughput Platform Speaker: Michael Teitell, MD, PhD, University of California Los Angeles (UCLA) Jonsson Comprehensive Cancer Center, Los Angeles, CA

9:00 Small Molecules Regulating Mitochondrial Translation Speaker: Brendan Battersby, PhD, University of Helsinki, Institute of Biotechnology, Helsinki, Finland

9:30 Vitamin B3/Niacin and Treatment of Mitochondrial Dysfunction Speaker: David J. Livingston, PhD, Brown University, Providence, RI

10:00 Break – Plaza Foyer

10:30 Ongoing Clinical Trials Updates (Patients and families will have the option to attend.) (See Saturday Abstract Schedule) – (Non CME)

12:30 Adjourn

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UMDF Mitochondrial Medicine 2019: Washington DC Oral Presentations and Lightning Talks – Abstracts

Wednesday, June 26, 2019 Platform Session #1: Abstracts - Opening and Organelle Cross-Talk and Mitochondrial Dynamics

Time Abstract# Presenter Title

11:15am PA-0530 Nam Chul Kim The PINK1/Parkin Pathway Mediates Dominant Mitochondrial Toxicity in CHCHD10-Induced ALS-FTD

11:30am PA-0582 Liam Coyne Protein Misfolding on the Inner Mitochondrial Membrane is Toxic and Has Pathological Consequences

11:45am PA-0539 Piotr Kopinski Regulation of Nuclear Epigenome by Mitochondrial DNA Heteroplasmy

12:00pm PA-0625 Cameron McKnight Using Human Pluripotent Stem Cell Models of Mitochondrial Disease to Identify Candidate Drug Treatments

12:15pm 10 Lightning – for the ONE Minute Lightning Talks see page 2, 3 and 4

Platform Session #2: Abstracts - Mitochondrial Architecture: Regulation and Maintenance

Time Abstract# Presenter Title

4:30pm PA-0551 Samantha Lewis Twinkle Helicase Selectively Interacts with the Inner Mitochondrial Membrane Lipid Cardiolipin to Scaffold Mtdna Replisome Recruitment at ER-Mitochondria Contact Sites

4:45pm PA-0552 Yan Burelle Coping with Respiratory Chain Deficiency Through Adaptive Optimization of the OXPHOS Assembly Line: Insights from the Hepatic LRPPRC Knockout Mouse Model.

5:00pm PA-0548 Kirsten Hoff A Novel Function for the Polymerase γ Accessory Subunit in Regulating mtDNA Copy Number

5:15pm 10 Lightning – for the ONE Minute Lightning Talks see page 2, 3 and 4

Thursday, June 27, 2019 Platform Session #5: Abstracts - Federal Updates on Research and Clinical Trials for Mitochondrial Disease

Time Abstract# Presenter Title

2:30pm PA-0544 Charles McCall Targeting the PDC/PDK Axis for Inflammatory Shock Syndromes in Inborn Errors of Metabolism

2:45pm PA-0580 Robert K. Naviaux

Elevated 1-deoxyceramides in Patients with MELAS and NARP—Testing a New Biomarker of Mitochondrial Dysfunction

3:00pm PA-0630 Amel Karaa Fatigue, Dizziness and Nausea: Doc I think I have Mito?

3:15pm 10 Lightning – for the ONE Minute Lightning Talks see page 2, 3 and 4

Friday, June 28, 2019 Platform Session #6: Abstracts - State of Mitochondrial Medicine (Scientific, Clinicians, Patients, Families, etc)

Time Abstract# Presenter Title

11:15am PA-0585 Peter Stacpoole The Changing Landscape of Clinical Trials for Primary Mitochondrial Diseases: 2011 to Present.

11:30am PA-0561 Claudia Pereira Gene Replacement Reverts Myopathy in Mouse Model with Mitochondrial Complex I-Deficient Muscle

UMDF Mitochondrial Medicine 2019 - Abstract Presentations Continued

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11:45am PA-0517 Stephen Thomas Development of the ProTide Prodrug CERC-913 as a Potential Treatment for Deoxyguanosine Kinase Deficiency

12:00pm PA-0554 Jirair Bedoyan Rationale and Feasibility of Newborn Screening for Pyruvate Dehydrogenase Complex Deficiencies

Saturday, June 29, 2019 Platform Session #8: Abstracts Bench to Bedside in Mitochondrial Disease and Clinical Trial Updates

Time Abstract# Presenter Title

10:30am PA-0621 Hilary Vernon TAZPOWER: Trial Results From a Randomized, Double-Blind, Placebo-Controlled, Crossover and Open-Label Extension Trial of Elamipretide in Patients With Barth Syndrome

10:45am PA-0607 Xavier Lloria Long-Term (Over 24 Months) Treatment With Idebenone May Continue to Improve Visual Function Response in Patients with Leber’s Hereditary Optic Neuropathy (LHON)

11:00am PA-0636 Xavier Lloria Pediatric Leber’s Hereditary Optic Neuropathy (LHON): Real-World Efficacy Results Following Long-Term Idebenone Treatment

11:15am PA-0631 Rustum Karanjia

Clinical Trial of Elamipretide Topical Ophthalmic Solution for the Treatment of Leber's Hereditary Optic Neuropathy

11:30am PA-0560 Matthew Klein Safety and Efficacy Clinical Trial of EPI-743 in Patients with Mitochondrial Disease and Epilepsy

11:45am PA-0521

Natalie Yivgi Ohana Mitochondrial Augmentation Therapy of Hematopoietic Stem Cells in Mitochondrial Deletion Syndromes: Preliminary Safety and Efficacy Demonstrated in First-in-Human Study

12:00pm PA-0598 Bruce Cohen MMPOWER-2 Open-Label Extension Trial: Results from 12 Months of Elamipretide Therapy in PMM Patients

12:15pm PA-0581 Amel Karaa MMPOWER-3 Trial Update: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial of Elamipretide in Patients With Primary Mitochondrial Myopathy

2019 Lightning ONE Minute Abstract Listing and Order of Presenters Wednesday, June 26 at 12:15pm Order Abstract # Presenter Name Title

1 2019 PA-0650 Sanna Matilainen Protein Hypersuccinylation Occurs In Succinyl-CoA Ligase Deficiency, and Leads to Disruption of Metabolic Networks Including Glycolysis

2 2019 PA-0534 Krish Chandrasekaran Nicotinamide Riboside is a Potential Therapy for Diabetic Neuropathy

3 2019 PA-0538 Tal Yardeni Mitochondrial Influence on the Gut Microbiota Community

4 2019 PA-0547 Fernando Scaglia Liver Transplant: Promising Therapeutic Approach for Patients with Ethylmalonic Encephalopathy

5 2019 PA-0549 David Bodenstein Role of Mitochondrial DNA Content and Oxidation in Bipolar Disorder Across Brain Regions

6 2019 PA-0550

Timothy Etheridge Mitochondria-Targeted Sulfide Delivery Molecules Improve Muscle Function in C.Elegans Models of Leigh Syndrome

UMDF Mitochondrial Medicine 2019 - Abstract Presentations Continued

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7 2019 PA-0555

Matt Whiteman Mitochondria-Targeted Sulfide Delivery Molecules Reverse Oxidative Damage In Friedreich’s Ataxia Fibroblasts

8 2019 PA-0618 Amel Karaa Are We Ready for Telehealth in Mitochondrial Medicine?

9 2019 PA-0564 Neal Mathew Characterization of Novel NDUFS2 and NUBPL Zebrafish Animal Models of Complex I Deficient Leigh Syndrome, with Validation of Therapeutic Leads Identified in Orthologous C. Elegans Models

Wednesday, June 26 at 5:15pm Order Abstract # Presenter Name Title

1 2019 PA-0569 Arianna Franca Anzmann

Multi-Omics Analysis of a New Cellular Model of Barth Syndrome Uncovers Mechanisms of Mitochondrial Dysfunction

2 2019 PA-0571 Tamas Kozicz Brain-On-A-Chip as a Disease Model of Impaired Neuronal Development And Network Function in Individuals With Mitochondrial Dysfunction

3 2019 PA-0573 Zarazuela Zolkipli Cunningham

The Significant Impact of Mitochondrial Myopathy Symptoms

4 2019 PA-0575 Gayatri Schur MRI Muscle-bone Phenotyping in Pediatric Mitochondrial Disease

5 2019 PA-0577 Metodi Metodiev Mutations in the MRPS28 Gene Encoding the Small Mitoribosomal Subunit Protein Bs1m in a Patient With Intrauterine Growth Retardation, Craniofacial Dysmorphism and Multisystemic Involvement

6 2019 PA-0586

George-Sankoh MMFP Tableau: Enabling Precision Medicine through Novel Integration, Visualization, and Complex Analytics of Clinical and Research Data

7 2019 PA-0590 Elizabeth McCormick Standardization of Leigh Syndrome Spectrum Definition and Application within the ClinGen Gene Clinical Validity Curation Framework

8 2019 PA-0601 Johan Van Hove Mutations in SQOR Encoding Sulfide:Quinone Oxidoreductase are a Potentially Treatable Cause of Leigh Disease

9 2019 PA-0602

Newell Belnap Investigation of a Recurrent Splice Site Mutation in Mitochondrial Methionyl-tRNA Formyl Transferase (MTFMT) Using Cellular and a Novel Mouse Model

10 2019 PA-0605 Nikol Volfova Mutations in the DNM1L gene (Drp1) and their Impact on the Mitochondria, Peroxisomes and Mitochondrial Energetic Metabolism

Thursday, June 27 at 3:15pm Order Abstract # Presenter Name Title

1 2019 PA-0606 Zarazuela Zolkipli-Cunningham

Quantitative Assessment of Mitochondrial Myopathy

2 2019 PA-0612 Wolf-Hagen Schunck Activation of Mitochondrial Quality Control by Epoxyeicosanoid-Like Drugs

3 2019 PA-0613 Senta Kapnick Understanding the Impact of mtDNA Copy Number Regulation on T Lymphocyte Metabolism and Function

4 2019 PA-0562 Lissa Poincenot Leber’s Hereditary Optic Neuropathy -- Not Just a Young Man's Disease

5 2019 PA-0649 Andre Mattman A Multi-Faceted Lifestyle Intervention for Mitochondrial A8344G Associated Multiple Symmetric Lipomatosis (MSL): Report of a Successful Patient Initiated Novel Therapy

UMDF Mitochondrial Medicine 2019 - Abstract Presentations Continued

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6 2019 PA-0627

Chynna Broxton Therapeutic Rescue Of Dld-Based Pyruvate Dehydrogenase Deficiency In Worm And Zebrafish Animal Models

7 2019 PA-0635 Olivia Kolenc Characterizing Metabolic Changes in Leigh’s Syndrome using Label-Free Multiphoton Microscopy

8 2019 PA-0642 Akira Ohtake 5-Aminolevulinic Acid and Fe can Bring a Permanent Cure for Mitochondrial Diseases: Basic Experiments and an Investigator Initiated Clinical Trial

9 2019 PA-0644 Min Peng N-Linked Glycosylation of MRS2 Inhibits Mitochondrial Magnesium Import

10 2019 PA-0647 Bruce Cohen Induced Pluripotent Stem Cells as Models for Studying Mitochondrial Disease

Important CME Information