1. A framework for translating tauopathy therapeutics: Drug discovery to clinical trials
- Author
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Feldman, Howard H, Cummings, Jeffrey L, Boxer, Adam L, Staffaroni, Adam M, Knopman, David S, Rizzo, Stacey J Sukoff, Territo, Paul R, Arnold, Steven E, Ballard, Clive, Beher, Dirk, Boeve, Bradley F, Dacks, Penny A, Diaz, Kristophe, Ewen, Colin, Fiske, Brian, Gonzalez, M Isabel, Harris, Glenn A, Hoffman, Beth J, Martinez, Terina N, McDade, Eric, Nisenbaum, Laura K, Palma, Jose‐Alberto, Quintana, Melanie, Rabinovici, Gil D, Rohrer, Jonathan D, Rosen, Howard J, Troyer, Matthew D, Kim, Doo Yeon, Tanzi, Rudolph E, Zetterberg, Henrik, Ziogas, Nick K, May, Patrick C, and Rommel, Amy
- Subjects
Biomedical and Clinical Sciences ,Biological Psychology ,Clinical Sciences ,Neurosciences ,Psychology ,Acquired Cognitive Impairment ,Frontotemporal Dementia (FTD) ,Aging ,Rare Diseases ,Alzheimer's Disease ,Dementia ,Neurodegenerative ,Brain Disorders ,Clinical Research ,Orphan Drug ,Alzheimer's Disease Related Dementias (ADRD) ,Clinical Trials and Supportive Activities ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,5.1 Pharmaceuticals ,Neurological ,Humans ,Tauopathies ,Drug Discovery ,Clinical Trials as Topic ,Biomarkers ,Translational Research ,Biomedical ,tau Proteins ,Drug Development ,biomarkers ,development ,early-phase clinical trials ,preclinical ,tauopathy ,therapeutics ,early‐phase clinical trials ,Geriatrics ,Clinical sciences ,Biological psychology - Abstract
The tauopathies are defined by pathological tau protein aggregates within a spectrum of clinically heterogeneous neurodegenerative diseases. The primary tauopathies meet the definition of rare diseases in the United States. There is no approved treatment for primary tauopathies. In this context, designing the most efficient development programs to translate promising targets and treatments from preclinical studies to early-phase clinical trials is vital. In September 2022, the Rainwater Charitable Foundation convened an international expert workshop focused on the translation of tauopathy therapeutics through early-phase trials. Our report on the workshop recommends a framework for principled drug development and a companion lexicon to facilitate communication focusing on reproducibility and achieving common elements. Topics include the selection of targets, drugs, biomarkers, participants, and study designs. The maturation of pharmacodynamic biomarkers to demonstrate target engagement and surrogate disease biomarkers is a crucial unmet need. HIGHLIGHTS: Experts provided a framework to translate therapeutics (discovery to clinical trials). Experts focused on the "5 Rights" (target, drug, biomarker, participants, trial). Current research on frontotemporal degeneration, progressive supranuclear palsy, and corticobasal syndrome therapeutics includes 32 trials (37% on biologics) Tau therapeutics are being tested in Alzheimer's disease; primary tauopathies have a large unmet need.
- Published
- 2024