Efficacy of sustained delivery of GC-1 from a Nanofluidic system in a spontaneously obese non-human primate: a case study
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.
KeywordsGC-1 Sobetirome Thyroid hormone mimetics Sustained release Non-human primate
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).
C.S.F. and A.G. designed the experiments. G.B. created the device schematics and performed the MRI analysis. C.S.F. and Z.W.S. performed the thyroid, pancreas, and liver imaging and analysis. A.A. and K.A.Y. performed the heart imaging and analysis. C.S.F., G.B., C.Y.X.C., A.B., M.F., and A.G. participated in drafting and/or revising of the manuscript. Primarily responsible for a particular specialized role (i) primate medicine: J.S., P.N.N., K.A.S., and L.R.H., (ii) blood processing: A.L.G., (iii) assisting with implantation: C.Y.X.C. and P.J.
Compliance with ethical standards
A.G. discloses a financial interest in NanoMedical Systems, Inc. All other authors declare no conflict of interest.
- Advia Centaur Assay Manual T3 111634 Rev. L, 2008Google Scholar
- Advia Centaur Assay Manual T4 111619 Rev. L, 2008Google Scholar
- S. Ayers, P. Webb, J. Endocrinol. Diabetes Obes. 2, 1042 (2014)Google Scholar
- S.A. Bauer, T.P. Arndt, K.E. Leslie, D.L. Pearl, P.V. Turner, Comp. Med. 61, 514 (2011)Google Scholar
- “Belviq,” can be found under https://www.drugs.com/belviq.html, 2017
- U.S. Food and Drug Administration, “Medications Target Long-Term Weight Control,” can be found under http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm312380.htm, 2015.
- A.J. Haertel, J.A. Stern, J.R. Reader, A. Spinner, J.A. Roberts, K.L. Christe, Comp. Med. 66, 333 (2016)Google Scholar
- R. Hubrecht, J. Kirkwood, Universities Federation for Animal Welfare, Eds., The UFAW Handbook on the Care and Management of Laboratory and Other Research Animals, Wiley-Blackwell, Chichester, 2010Google Scholar
- K.L. Jen, B.C. Hansen, B.L. Metzger, Int. J. Obes. 9, 213 (1985)Google Scholar
- A. Krosnick, Prim. Care 15, 423 (1988)Google Scholar
- Mayo Foundation for Medical Education and Research, “Common weight-loss drugs,” can be found under http://www.mayoclinic.org/healthy-lifestyle/weight-loss/in-depth/weight-loss-drugs/art-20044832?pg=2, n.d.
- A. Natalicchio, N. Marrano, G. Biondi, R. Spagnuolo, R. Labarbuta, I. Porreca, A. Cignarelli, M. Bugliani, P. Marchetti, S. Perrini, L. Laviola, F. Giorgino, Diabetes 2017, db170002Google Scholar
- Y. Okauchi, H. Iwahashi, K. Okita, T. Funahashi, K. Kishida, M. Noguchi, T. Ohira, T. Nakamura, A. Imagawa, I. Shimomura, J. Diabetes, Investig. 4, 454 (2013)Google Scholar
- T.S. Scanlan, Safety and Pharmacodynamic Study of Sobetirome in X-Linked Adrenoleukodystrophy (X-ALD) (US, Oregon, 2013)Google Scholar
- Scanlan, T. S., Hartley, M., Placzek, A., Righi, M., Use of Sobetirome in the Treatment of X-Linked Adrenolenoleukodystrophy, n.d.Google Scholar
- A. Shoemaker, Sci. Transl. Med. 2017, 9, eaao2263Google Scholar
- L. Summers, K.J. Clingerman, X. Yang, J. Am. Assoc. Lab. Anim. Sci. JAALAS 51, 88 (2012)Google Scholar
- Miriam E. Tucker, “FDA Approves Novel Implanted Device for Treating Obesity,” can be found under http://www.medscape.com/viewarticle/838176, 2015.
- C. P. Vega, C. M. Apovian, can be found under http://www.medscape.com/viewarticle/875655, n.d.
- D. Wescott, J. Hennan, D. Pavlock, J. Dipiero, D. Bounous, Clin. Chem. 58, A50 (2012)Google Scholar
- S. Wolfensohn, in UFAW Handb. Care Manag. Lab. Res. Anim. Eight Ed., n.d.Google Scholar
- A.H. Wu, Y.J. Feng, J.H. Contois, S. Pervaiz, Ann. Clin. Lab. Sci. 26, 291 (1996)Google Scholar