Improving translatability of preclinical studies for neuromuscular disorders: lessons from the TREAT-NMD Advisory Committee for Therapeutics (TACT)

Disease Models & Mechanisms

Kathryn R. Wagner¹  Cristina Csimma²  Volker Straub³  Joanne Lee³  Cathy Turner³  Dominic J. Wells⁴  Miranda D. Grounds⁵  Kanneboyina Nagaraju⁶  Raffaella Willmann⁷  Annamaria De Luca⁸  Annemieke Aartsma-Rus⁹  Maaike van Putten⁹  James Dowling⁹ 

[1] Center for Genetic Muscle Disorders, Kennedy Krieger Institute and the Departments of Neurology and Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA;Csimma LLC, Lincoln, MA 01773, USA;John Walton Muscular Dystrophy Research Centre, Centre for Life, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE7 7DN, UK;Neuromuscular Disease Group, Royal Veterinary College, London NW1 0TU, UK;School of Human Sciences, The University of Western Australia, Perth, WA 6009, Australia;School of Pharmacy and Pharmaceutical Sciences, Binghamton University, New York, NY 13902-6000, USA;Swiss Foundation for Research on Muscle Diseases, 2016 Cortaillod, Switzerland;Unit of Pharmacology, Department of Pharmacy and Drug Sciences, University of Bari Aldo Moro, 70125 Bari, Italy;;

关键词: animal models;    preclinical;    guidelines;    efficacy studies;    clinical trial;    standard protocols;    neuromuscular;   

DOI  :  10.1242/dmm.042903

来源: DOAJ

【 摘 要 】

Clinical trials for rare neuromuscular diseases imply, among other investments, a high emotional burden for the whole disease community. Translation of data from preclinical studies to justify any clinical trial must be carefully pondered in order to minimize the risk of clinical trial withdrawal or failure. A rigorous distinction between proof-of-concept and preclinical efficacy studies using animal models is key to support the rationale of a clinical trial involving patients. This Review evaluates the experience accumulated by the TREAT-NMD Advisory Committee for Therapeutics, which provides detailed constructive feedback on clinical proposals for neuromuscular diseases submitted by researchers in both academia and industry, and emphasizes that a timely critical review of preclinical efficacy data from animal models, including biomarkers for specific diseases, combined with adherence to existing guidelines and standard protocols, can significantly help to de-risk clinical programs and prevent disappointments and costly engagement.

【 授权许可】

Unknown