Adam L Boxer1, Michael Gold2, Howard Feldman3, Bradley F Boeve4, Susan L-J Dickinson5, Howard Fillit6, Carole Ho7, Robert Paul8, Rodney Pearlman9, Margaret Sutherland10, Ajay Verma11, Stephen P Arneric12, Brian M Alexander13, Bradford C Dickerson14, Earl Ray Dorsey15, Murray Grossman16, Edward D Huey17, Michael C Irizarry18, William J Marks19, Mario Masellis20,21, Frances McFarland22, Debra Niehoff5, Chiadi U Onyike23, Sabrina Paganoni24, Michael A Panzara25, Kenneth Rockwood26, Jonathan D Rohrer27, Howard Rosen1, Robert N Schuck28, Holly D Soares29, Nadine Tatton5. 1. Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA. 2. Development Neurosciences, AbbVie, Chicago, IL, USA. 3. Department of Neurosciences, University of California San Diego, San Diego, CA, USA. 4. Department of Neurology, Mayo Clinic, Rochester, MN, USA. 5. Association for Frontotemporal Degeneration, Radnor, PA, USA. 6. Alzheimer's Drug Discovery Foundation, New York, NY, USA. 7. Denali Therapeutics, San Francisco, CA, USA. 8. Alector, Inc., South San Francisco, CA, USA. 9. The Bluefield Project, San Francisco, CA, USA. 10. Chan Zuckerberg Initiative, Redwood City, CA, USA. 11. United Neuroscience, Dublin, Ireland. 12. Critical Path Institute, Tucson, AZ, USA. 13. Dana-Farber Cancer Institute, Harvard University, Boston, MA, USA. 14. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. 15. Center for Health and Technology, University of Rochester, Rochester, NY, USA. 16. Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA. 17. Departments of Psychiatry and Neurology, Columbia University, NY, USA. 18. Formerly of Early Phase Neurosciences, Eli Lilly, Indianapolis, IN, USA. 19. Clinical Neurology, Verily Life Sciences, South San Francisco, CA, USA. 20. Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, ON, Canada. 21. Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, University of Toronto, ON, Canada. 22. McFarland Writing, Annapolis, MD, USA. 23. Department Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins University, Baltimore, MD, USA. 24. Healey Center for ALS, Massachusetts General Hospital, Boston, MA, USA. 25. Development, Wave Life Sciences, Boston, MA, USA. 26. Division of Geriatric Medicine, Dalhousie University, Halifax, NS, Canada. 27. Dementia Research Centre, UCL Institute of Neurology, Queen Square, London, UK. 28. Office of Clinical Pharmacology, Center for Drug Evaluation and Research, FDA, Silver Spring, MD, USA. 29. Department of Neurology, AbbVie, Chicago, IL, USA.
Abstract
INTRODUCTION: Frontotemporal lobar degeneration (FTLD) is the most common form of dementia for those under 60 years of age. Increasing numbers of therapeutics targeting FTLD syndromes are being developed. METHODS: In March 2018, the Association for Frontotemporal Degeneration convened the Frontotemporal Degeneration Study Group meeting in Washington, DC, to discuss advances in the clinical science of FTLD. RESULTS: Challenges exist for conducting clinical trials in FTLD. Two of the greatest challenges are (1) the heterogeneity of FTLD syndromes leading to difficulties in efficiently measuring treatment effects and (2) the rarity of FTLD disorders leading to recruitment challenges. DISCUSSION: New personalized endpoints that are clinically meaningful to individuals and their families should be developed. Personalized approaches to analyzing MRI data, development of new fluid biomarkers and wearable technologies will help to improve the power to detect treatment effects in FTLD clinical trials and enable new, clinical trial designs, possibly leveraged from the experience of oncology trials. A computational visualization and analysis platform that can support novel analyses of combined clinical, genetic, imaging, biomarker data with other novel modalities will be critical to the success of these endeavors.
INTRODUCTION: Frontotemporal lobar degeneration (FTLD) is the most common form of dementia for those under 60 years of age. Increasing numbers of therapeutics targeting FTLD syndromes are being developed. METHODS: In March 2018, the Association for Frontotemporal Degeneration convened the Frontotemporal Degeneration Study Group meeting in Washington, DC, to discuss advances in the clinical science of FTLD. RESULTS: Challenges exist for conducting clinical trials in FTLD. Two of the greatest challenges are (1) the heterogeneity of FTLD syndromes leading to difficulties in efficiently measuring treatment effects and (2) the rarity of FTLD disorders leading to recruitment challenges. DISCUSSION: New personalized endpoints that are clinically meaningful to individuals and their families should be developed. Personalized approaches to analyzing MRI data, development of new fluid biomarkers and wearable technologies will help to improve the power to detect treatment effects in FTLD clinical trials and enable new, clinical trial designs, possibly leveraged from the experience of oncology trials. A computational visualization and analysis platform that can support novel analyses of combined clinical, genetic, imaging, biomarker data with other novel modalities will be critical to the success of these endeavors.
Authors: Elizabeth C Finger; Julia MacKinley; Mervin Blair; Lindsay D Oliver; Sarah Jesso; Maria C Tartaglia; Michael Borrie; Jennie Wells; Isabel Dziobek; Stephen Pasternak; Derek G V Mitchell; Katherine Rankin; Andrew Kertesz; Adam Boxer Journal: Neurology Date: 2014-12-10 Impact factor: 9.910
Authors: Kelly L Andrzejewski; Ariel V Dowling; David Stamler; Timothy J Felong; Denzil A Harris; Cynthia Wong; Hang Cai; Ralf Reilmann; Max A Little; Joseph T Gwin; Kevin M Biglan; E Ray Dorsey Journal: J Huntingtons Dis Date: 2016-06-18
Authors: Kamalini G Ranasinghe; Katherine P Rankin; Peter S Pressman; David C Perry; Iryna V Lobach; William W Seeley; Giovanni Coppola; Anna M Karydas; Lea T Grinberg; Tal Shany-Ur; Suzee E Lee; Gil D Rabinovici; Howard J Rosen; Maria Luisa Gorno-Tempini; Adam L Boxer; Zachary A Miller; Winston Chiong; Mary DeMay; Joel H Kramer; Katherine L Possin; Virginia E Sturm; Brianne M Bettcher; Michael Neylan; Diana D Zackey; Lauren A Nguyen; Robin Ketelle; Nikolas Block; Teresa Q Wu; Alison Dallich; Natanya Russek; Alyssa Caplan; Daniel H Geschwind; Keith A Vossel; Bruce L Miller Journal: JAMA Neurol Date: 2016-09-01 Impact factor: 18.302
Authors: Günter U Höglinger; Gesine Respondek; Maria Stamelou; Carolin Kurz; Keith A Josephs; Anthony E Lang; Brit Mollenhauer; Ulrich Müller; Christer Nilsson; Jennifer L Whitwell; Thomas Arzberger; Elisabet Englund; Ellen Gelpi; Armin Giese; David J Irwin; Wassilios G Meissner; Alexander Pantelyat; Alex Rajput; John C van Swieten; Claire Troakes; Angelo Antonini; Kailash P Bhatia; Yvette Bordelon; Yaroslau Compta; Jean-Christophe Corvol; Carlo Colosimo; Dennis W Dickson; Richard Dodel; Leslie Ferguson; Murray Grossman; Jan Kassubek; Florian Krismer; Johannes Levin; Stefan Lorenzl; Huw R Morris; Peter Nestor; Wolfgang H Oertel; Werner Poewe; Gil Rabinovici; James B Rowe; Gerard D Schellenberg; Klaus Seppi; Thilo van Eimeren; Gregor K Wenning; Adam L Boxer; Lawrence I Golbe; Irene Litvan Journal: Mov Disord Date: 2017-05-03 Impact factor: 10.338
Authors: Clifford R Jack; David A Bennett; Kaj Blennow; Maria C Carrillo; Billy Dunn; Samantha Budd Haeberlein; David M Holtzman; William Jagust; Frank Jessen; Jason Karlawish; Enchi Liu; Jose Luis Molinuevo; Thomas Montine; Creighton Phelps; Katherine P Rankin; Christopher C Rowe; Philip Scheltens; Eric Siemers; Heather M Snyder; Reisa Sperling Journal: Alzheimers Dement Date: 2018-04 Impact factor: 21.566
Authors: Peter A Ljubenkov; Adam M Staffaroni; Julio C Rojas; Isabel E Allen; Ping Wang; Hilary Heuer; Anna Karydas; John Kornak; Yann Cobigo; William W Seeley; Lea T Grinberg; Salvatore Spina; Anne M Fagan; Gina Jerome; David Knopman; Brad F Boeve; Bradford C Dickerson; Joel Kramer; Bruce Miller; Adam L Boxer; Howard J Rosen Journal: Ann Clin Transl Neurol Date: 2018-09-20 Impact factor: 4.511
Authors: W Ryan Powell; William R Buckingham; Jamie L Larson; Leigha Vilen; Menggang Yu; M Shahriar Salamat; Barbara B Bendlin; Robert A Rissman; Amy J H Kind Journal: JAMA Netw Open Date: 2020-06-01
Authors: Marta Del Campo; Yolande A L Pijnenburg; Alice Chen-Plotkin; David J Irwin; Murray Grossman; Harry A M Twaalfhoven; William T Hu; Lieke H Meeter; John van Swieten; Lisa Vermunt; Frans Martens; Annemieke C Heijboer; Charlotte E Teunissen Journal: Biomolecules Date: 2021-10-08
Authors: Ignacio Illán-Gala; Victor Montal; Sergi Borrego-Écija; Maria Luisa Mandelli; Neus Falgàs; Ariane E Welch; Jordi Pegueroles; Miguel Santos-Santos; Alexandre Bejanin; Daniel Alcolea; Oriol Dols-Icardo; Olivia Belbin; Mª Belén Sánchez-Saudinós; Nuria Bargalló; Sofía González-Ortiz; Albert Lladó; Rafael Blesa; Bradford C Dickerson; Howard J Rosen; Bruce L Miller; Alberto Lleó; Maria Luisa Gorno-Tempini; Raquel Sánchez-Valle; Juan Fortea Journal: Alzheimers Res Ther Date: 2022-02-09 Impact factor: 6.982
Authors: Helen Shiells; Bjoern O Schelter; Peter Bentham; Thomas C Baddeley; Christopher M Rubino; Harish Ganesan; Jeffrey Hammel; Vesna Vuksanovic; Roger T Staff; Alison D Murray; Luc Bracoud; Damon J Wischik; Gernot Riedel; Serge Gauthier; Jianping Jia; Hans J Moebius; Jiri Hardlund; Christopher M Kipps; Karin Kook; John M D Storey; Charles R Harrington; Claude M Wischik Journal: J Alzheimers Dis Date: 2020 Impact factor: 4.472
Authors: Michelle A Johnson; Qiudong Deng; Georgia Taylor; Zachary T McEachin; Anthony W S Chan; Jessica Root; Gary J Bassell; Thomas Kukar Journal: Neurobiol Dis Date: 2020-09-18 Impact factor: 5.996
Authors: Lauren G Friedman; Nicholas McKeehan; Yuko Hara; Jeffrey L Cummings; Dawn C Matthews; Jian Zhu; Richard C Mohs; Deli Wang; Suzanne B Hendrix; Melanie Quintana; Lon S Schneider; Michael Grundman; Samuel P Dickson; Howard H Feldman; Judith Jaeger; Elizabeth C Finger; J Michael Ryan; Debra Niehoff; Susan L-J Dickinson; Jessica T Markowitz; Meriel Owen; Alessio Travaglia; Howard M Fillit Journal: Neurology Date: 2021-03-05 Impact factor: 9.910