TY - JOUR
T1 - Biophysical analysis of drug efficacy on C. elegans models for neurodegenerative and neuromuscular diseases
AU - Sofela, Samuel
AU - Sahloul, Sarah
AU - Song, Yong Ak
N1 - Funding Information:
Funding: Y.-A. Song received grant support for this work from the Al Jalila Foundation [AJF201633]. S. Sofela was supported by the NYUAD Global PhD Student Fellowship program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2021 Sofela et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/6
Y1 - 2021/6
N2 - Caenorhabditis elegans has emerged as a powerful model organism for drug screening due to its cellular simplicity, genetic amenability and homology to humans combined with its small size and low cost. Currently, high-throughput drug screening assays are mostly based on image-based phenotyping with the focus on morphological-descriptive traits not exploiting key locomotory parameters of this multicellular model with muscles such as its thrashing force, a critical biophysical parameter when screening drugs for muscle-related diseases. In this study, we demonstrated the use of a micropillar-based force assay chip in combination with a fluorescence assay to evaluate the efficacy of various drugs currently used in treatment of neurodegenerative and neuromuscular diseases. Using this two-dimensional approach, we showed that the force assay was generally more sensitive in measuring efficacy of drug treatment in Duchenne Muscular Dystrophy and Parkinson’s Disease mutant worms as well as partly in Amyotrophic Lateral Sclerosis model. These results underline the potential of our force assay chip in screening of potential drug candidates for the treatment of neurodegenerative and neuromuscular diseases when combined with a fluorescence assay in a two-dimensional analysis approach.
AB - Caenorhabditis elegans has emerged as a powerful model organism for drug screening due to its cellular simplicity, genetic amenability and homology to humans combined with its small size and low cost. Currently, high-throughput drug screening assays are mostly based on image-based phenotyping with the focus on morphological-descriptive traits not exploiting key locomotory parameters of this multicellular model with muscles such as its thrashing force, a critical biophysical parameter when screening drugs for muscle-related diseases. In this study, we demonstrated the use of a micropillar-based force assay chip in combination with a fluorescence assay to evaluate the efficacy of various drugs currently used in treatment of neurodegenerative and neuromuscular diseases. Using this two-dimensional approach, we showed that the force assay was generally more sensitive in measuring efficacy of drug treatment in Duchenne Muscular Dystrophy and Parkinson’s Disease mutant worms as well as partly in Amyotrophic Lateral Sclerosis model. These results underline the potential of our force assay chip in screening of potential drug candidates for the treatment of neurodegenerative and neuromuscular diseases when combined with a fluorescence assay in a two-dimensional analysis approach.
KW - Animals
KW - Caenorhabditis elegans
KW - Disease Models, Animal
KW - Neurodegenerative Diseases/drug therapy
KW - Neuromuscular Diseases/drug therapy
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U2 - 10.1371/journal.pone.0246496
DO - 10.1371/journal.pone.0246496
M3 - Article
C2 - 34115761
AN - SCOPUS:85107900955
SN - 1932-6203
VL - 16
JO - PLoS One
JF - PLoS One
IS - 6
M1 - e0246496
ER -