title: The effects of an ActRIIb receptor Fc fusion protein ligand trap in juvenile simian immunodeficiency virus-infected rhesus macaques.
abstract: There are no approved therapies for muscle wasting in children infected with human immunodeficiency virus (HIV), which portends poor disease outcomes. To determine whether a soluble ActRIIb receptor Fc fusion protein (ActRIIB.Fc), a ligand trap for TGF-β/activin family members including myostatin, can prevent or restore loss of lean body mass and body weight in simian immunodeficiency virus (SIV)-infected juvenile rhesus macaques (Macaca mulatta). Fourteen pair-housed, juvenile male rhesus macaques were inoculated with SIVmac239 and, 4 wk postinoculation (WPI) treated with intramuscular injections of 10 mg ⋅ kg(-1) ⋅ wk(-1) ActRIIB.Fc or saline placebo. Body weight, lean body mass, SIV titers, and somatometric measurements were assessed monthly for 16 wk. Age-matched SIV-infected rhesus macaques were injected with saline. Intervention groups did not differ at baseline. Gains in lean mass were significantly greater in the ActRIIB.Fc group than in the placebo group (P < 0.001). Administration of ActRIIB.Fc was associated with greater gains in body weight (P = 0.01) and upper arm circumference than placebo. Serum CD4(+) T-lymphocyte counts and SIV copy numbers did not differ between groups. Administration of ActRIIB.Fc was associated with higher muscle expression of myostatin than placebo. ActRIIB.Fc effectively blocked and reversed loss of body weight, lean mass, and fat mass in juvenile SIV-infected rhesus macaques.
authors.affiliation: *Department of Comparative Pathology, New England Primate Research Center, Southborough, Massachusetts, USA; and Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Karyn E
authors.initials: KE
authors.lastname: O'Connell
authors.affiliation: *Department of Comparative Pathology, New England Primate Research Center, Southborough, Massachusetts, USA; and Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Guo
authors.affiliation: *Department of Comparative Pathology, New England Primate Research Center, Southborough, Massachusetts, USA; and Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Carlo
authors.initials: C
authors.lastname: Serra
authors.affiliation: *Department of Comparative Pathology, New England Primate Research Center, Southborough, Massachusetts, USA; and Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Beck
authors.affiliation: *Department of Comparative Pathology, New England Primate Research Center, Southborough, Massachusetts, USA; and Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Wachtman
authors.affiliation: *Department of Comparative Pathology, New England Primate Research Center, Southborough, Massachusetts, USA; and Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Hoggatt
authors.affiliation: *Department of Comparative Pathology, New England Primate Research Center, Southborough, Massachusetts, USA; and Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Dongling
authors.initials: D
authors.lastname: Xia
authors.affiliation: *Department of Comparative Pathology, New England Primate Research Center, Southborough, Massachusetts, USA; and Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Pearson
authors.affiliation: *Department of Comparative Pathology, New England Primate Research Center, Southborough, Massachusetts, USA; and Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Knight
authors.affiliation: *Department of Comparative Pathology, New England Primate Research Center, Southborough, Massachusetts, USA; and Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Micheal
authors.initials: M
authors.lastname: O'Connell
authors.affiliation: *Department of Comparative Pathology, New England Primate Research Center, Southborough, Massachusetts, USA; and Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Miller
authors.affiliation: *Department of Comparative Pathology, New England Primate Research Center, Southborough, Massachusetts, USA; and Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Westmoreland
authors.affiliation: *Department of Comparative Pathology, New England Primate Research Center, Southborough, Massachusetts, USA; and Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA sbhasin@partners.org.
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
mesh_terms: D030301:Activin Receptors, Type II / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D019247:HIV Wasting Syndrome / Q000517:prevention & control; D006400:Hematocrit; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000627:therapeutic use*; D008024:Ligands; D008253:Macaca mulatta; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D055435:Myostatin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D015302:Simian Immunodeficiency Virus; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D015854:Up-Regulation; D015430:Weight Gain
chemical_list: D007141:Immunoglobulin Fc Fragments; D008024:Ligands; D055435:Myostatin; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B
keywords: AIDS; HIV; cachexia; muscle wasting; nonhuman primate