Efficacy of sustained delivery of GC-1 from a Nanofluidic system in a spontaneously obese non-human primate: a case study

Carly S. Filgueira; Giacomo Bruno; Zachary W. Smith; Corrine Ying Xuan Chua; Andrea Ballerini; Marco Folci; April L. Gilbert; Priya Jain; Jagannadha K. Sastry; Pramod N. Nehete; Kathryn A. Shelton; Lori R. Hill; Areeba Ali; Keith A. Youker; Alessandro Grattoni

doi:10.1007/s10544-018-0296-2

Efficacy of sustained delivery of GC-1 from a Nanofluidic system in a spontaneously obese non-human primate: a case study

Carly S. Filgueira, Giacomo Bruno, Zachary W. Smith, Corrine Ying Xuan Chua, Andrea Ballerini, Marco Folci, April L. Gilbert, Priya Jain, Jagannadha K. Sastry, Pramod N. Nehete, Kathryn A. Shelton, Lori R. Hill, Areeba Ali, Keith A. Youker, Alessandro Grattoni

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

With nearly 40% of U.S. adults obese, and childhood and adolescent rates rising, obesity and associated comorbidities are serious public health concerns with massive societal costs. Often, lifestyle interventions do not offer sufficient weight loss to improve health, requiring surgery and medications as adjunct management strategies. Here, we present a 4-month case study in which the sustained, low-dose, and constant administration of the thyroid receptor β selective agonist GC-1 (sobetirome) from a novel nanochannel membrane implant was assessed in an obese, pre-diabetic rhesus macaque. Dramatic loss of white adipose tissue in the abdomen from 36 to 18% was observed via magnetic resonance imaging in conjunction with normalized serum insulin and glycemia, with no signs of cardiotoxicity shown. The non-human primate study highlights sustained low-dose delivery of GC-1 from our minimally invasive subcutaneous implant as a valuable approach to induce weight loss and manage obesity and comorbidities, including type 2 diabetes.

Original language	English (US)
Article number	49
Journal	Biomedical Microdevices
Volume	20
Issue number	2
DOIs	https://doi.org/10.1007/s10544-018-0296-2
State	Published - Jun 1 2018

Keywords

GC-1
Non-human primate
Sobetirome
Sustained release
Thyroid hormone mimetics

ASJC Scopus subject areas

Biomedical Engineering
Molecular Biology

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10.1007/s10544-018-0296-2

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Filgueira, C. S., Bruno, G., Smith, Z. W., Chua, C. Y. X., Ballerini, A., Folci, M., Gilbert, A. L., Jain, P., Sastry, J. K., Nehete, P. N., Shelton, K. A., Hill, L. R., Ali, A., Youker, K. A., & Grattoni, A. (2018). Efficacy of sustained delivery of GC-1 from a Nanofluidic system in a spontaneously obese non-human primate: a case study. Biomedical Microdevices, 20(2), Article 49. https://doi.org/10.1007/s10544-018-0296-2

Filgueira, CS, Bruno, G, Smith, ZW, Chua, CYX, Ballerini, A, Folci, M, Gilbert, AL, Jain, P, Sastry, JK, Nehete, PN, Shelton, KA, Hill, LR, Ali, A, Youker, KA & Grattoni, A 2018, 'Efficacy of sustained delivery of GC-1 from a Nanofluidic system in a spontaneously obese non-human primate: a case study', Biomedical Microdevices, vol. 20, no. 2, 49. https://doi.org/10.1007/s10544-018-0296-2

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title = "Efficacy of sustained delivery of GC-1 from a Nanofluidic system in a spontaneously obese non-human primate: a case study",

abstract = "With nearly 40% of U.S. adults obese, and childhood and adolescent rates rising, obesity and associated comorbidities are serious public health concerns with massive societal costs. Often, lifestyle interventions do not offer sufficient weight loss to improve health, requiring surgery and medications as adjunct management strategies. Here, we present a 4-month case study in which the sustained, low-dose, and constant administration of the thyroid receptor β selective agonist GC-1 (sobetirome) from a novel nanochannel membrane implant was assessed in an obese, pre-diabetic rhesus macaque. Dramatic loss of white adipose tissue in the abdomen from 36 to 18% was observed via magnetic resonance imaging in conjunction with normalized serum insulin and glycemia, with no signs of cardiotoxicity shown. The non-human primate study highlights sustained low-dose delivery of GC-1 from our minimally invasive subcutaneous implant as a valuable approach to induce weight loss and manage obesity and comorbidities, including type 2 diabetes.",

keywords = "GC-1, Non-human primate, Sobetirome, Sustained release, Thyroid hormone mimetics",

author = "Filgueira, {Carly S.} and Giacomo Bruno and Smith, {Zachary W.} and Chua, {Corrine Ying Xuan} and Andrea Ballerini and Marco Folci and Gilbert, {April L.} and Priya Jain and Sastry, {Jagannadha K.} and Nehete, {Pramod N.} and Shelton, {Kathryn A.} and Hill, {Lori R.} and Areeba Ali and Youker, {Keith A.} and Alessandro Grattoni",

note = "Funding Information: Acknowledgements The authors would like to acknowledge Drs. Kevin Phillips, Jean Lin, Paul Webb, Eugenia Nicolov, and Omaima Sabek for early discussions and project developments, Carlos Favela and Dr. Kemi Cui from the advanced cellular and tissue microscopy core, Dr. Andreana Rivera, Sandra Steptoe, and Dr. Yuelan Ren from the research pathology core. We also thank Dr. Greg Wilkerson, Luke Segura, Elizabeth Lindemann, and Debra Larsen from the Michale E. Keeling Center for Comparative Medicine and Research at MD Anderson Cancer Center, Dr. Yongying Jiang from the Pharmaceutical Science Facility, Institute of Applied Cancer Science, UT MD Anderson Cancer Center, and Dr. Jingfei Ma, Lindsay Wilson, and Michelle Underwood from MD Anderson Cancer Center. Membranes were provided by NanoMedical Systems, Inc. This work was supported by funds from Houston Methodist Research Institute (AG). Publisher Copyright: {\textcopyright} 2018, Springer Science+Business Media, LLC, part of Springer Nature. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",

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doi = "10.1007/s10544-018-0296-2",

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T2 - a case study

AU - Filgueira, Carly S.

AU - Bruno, Giacomo

AU - Smith, Zachary W.

AU - Chua, Corrine Ying Xuan

AU - Ballerini, Andrea

AU - Folci, Marco

AU - Gilbert, April L.

AU - Jain, Priya

AU - Sastry, Jagannadha K.

AU - Nehete, Pramod N.

AU - Shelton, Kathryn A.

AU - Hill, Lori R.

AU - Ali, Areeba

AU - Youker, Keith A.

AU - Grattoni, Alessandro

N1 - Funding Information: Acknowledgements The authors would like to acknowledge Drs. Kevin Phillips, Jean Lin, Paul Webb, Eugenia Nicolov, and Omaima Sabek for early discussions and project developments, Carlos Favela and Dr. Kemi Cui from the advanced cellular and tissue microscopy core, Dr. Andreana Rivera, Sandra Steptoe, and Dr. Yuelan Ren from the research pathology core. We also thank Dr. Greg Wilkerson, Luke Segura, Elizabeth Lindemann, and Debra Larsen from the Michale E. Keeling Center for Comparative Medicine and Research at MD Anderson Cancer Center, Dr. Yongying Jiang from the Pharmaceutical Science Facility, Institute of Applied Cancer Science, UT MD Anderson Cancer Center, and Dr. Jingfei Ma, Lindsay Wilson, and Michelle Underwood from MD Anderson Cancer Center. Membranes were provided by NanoMedical Systems, Inc. This work was supported by funds from Houston Methodist Research Institute (AG). Publisher Copyright: © 2018, Springer Science+Business Media, LLC, part of Springer Nature. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.

PY - 2018/6/1

Y1 - 2018/6/1

N2 - With nearly 40% of U.S. adults obese, and childhood and adolescent rates rising, obesity and associated comorbidities are serious public health concerns with massive societal costs. Often, lifestyle interventions do not offer sufficient weight loss to improve health, requiring surgery and medications as adjunct management strategies. Here, we present a 4-month case study in which the sustained, low-dose, and constant administration of the thyroid receptor β selective agonist GC-1 (sobetirome) from a novel nanochannel membrane implant was assessed in an obese, pre-diabetic rhesus macaque. Dramatic loss of white adipose tissue in the abdomen from 36 to 18% was observed via magnetic resonance imaging in conjunction with normalized serum insulin and glycemia, with no signs of cardiotoxicity shown. The non-human primate study highlights sustained low-dose delivery of GC-1 from our minimally invasive subcutaneous implant as a valuable approach to induce weight loss and manage obesity and comorbidities, including type 2 diabetes.

AB - With nearly 40% of U.S. adults obese, and childhood and adolescent rates rising, obesity and associated comorbidities are serious public health concerns with massive societal costs. Often, lifestyle interventions do not offer sufficient weight loss to improve health, requiring surgery and medications as adjunct management strategies. Here, we present a 4-month case study in which the sustained, low-dose, and constant administration of the thyroid receptor β selective agonist GC-1 (sobetirome) from a novel nanochannel membrane implant was assessed in an obese, pre-diabetic rhesus macaque. Dramatic loss of white adipose tissue in the abdomen from 36 to 18% was observed via magnetic resonance imaging in conjunction with normalized serum insulin and glycemia, with no signs of cardiotoxicity shown. The non-human primate study highlights sustained low-dose delivery of GC-1 from our minimally invasive subcutaneous implant as a valuable approach to induce weight loss and manage obesity and comorbidities, including type 2 diabetes.

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ER -

Efficacy of sustained delivery of GC-1 from a Nanofluidic system in a spontaneously obese non-human primate: a case study

Abstract

Keywords

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