Results 1 to 6 of 6

Thread: Ace-031

  1. #1
    Future Sexy Campeon
    Join Date
    Dec 2010
    Posts
    1,721
    Rep Power
    0

    Default Ace-031

    ACE-031 is a novel, muscle-building agent that is being developed for the treatment of patients with Duchenne Muscular Dystrophy with the goal of improving strength and preserving physical function.
    What is ACE-031?
    ACE-031 is an investigational protein therapeutic that builds muscle and increases strength by inhibiting molecules that bind to and signal through a cell surface receptor called Activin Receptor Type IIB (ActRIIB). It is a recombinant fusion protein that is produced by joining a portion of the human ActRIIB receptor to a portion of a human antibody. This creates a freely circulating, decoy version of ActRIIB which removes proteins, such as GDF-8 (myostatin) and other related molecules that limit the growth and strength of muscle.
    The Role of ActRIIB Signaling and Muscle Growth
    Muscle growth is regulated by proteins in the TGF-β protein superfamily that serve as “on” or “off” switches for muscle production. Several molecules including GDF-8 interact with the ActRIIB receptor and send an “off” signal to stop muscle production. In the absence of these “off” switch molecules that signal through the ActRIIB receptor, muscle mass increases dramatically.
    Decreased ActRIIB Signaling Results in Muscle Growth
    In nature, this effect has been observed in numerous species, particularly in animals that have been bred for increased musculature and strength. For example, Belgian Blue cattle lack the gene for GDF-8, which is one of several molecules that activate the ActRIIB receptor. A deficiency of this protein results in cattle with tremendously developed musculature and strength. Similar effects have been observed in other species, including rodents, dogs and even humans.
    ACE-031 Builds Skeletal Muscle
    Treatment with ACE-031 promotes muscle growth by inhibiting ActRIIB signaling. It binds to proteins that signal through the ActRIIB receptor to limit muscle growth. When it binds to these proteins, it prevents them from interacting with the ActRIIB receptor, thus allowing muscle to grow. Moreover, because it prevents GDF-8 and other proteins that regulate muscle mass from signaling through the ActRIIB receptor, its effects on lean muscle exceed those of inhibitors of GDF-8 (myostatin) alone.
    When animals are treated with ACE-031, they experience growth in lean muscle and are considerably stronger than their untreated counterparts. This has been shown in several species, and in both healthy animals and in animals with diseases associated with muscle weakness and wasting.
    Clinical Development Status
    Acceleron has completed a single dose study (A031-01) of ACE-031 in healthy volunteers. A second study in healthy volunteers (A031-02), evaluating multiple doses of ACE-031, has been completed
    A Phase 2 study in patients with Duchenne Muscular Dystrophy (A031-03) was initiated in Canada. The main purpose of this study is to determine if ACE-031 is safe and well-tolerated in children with DMD. Another purpose of this study is to obtain preliminary information regarding the effects of it on muscle size, strength, and function in patients with DMD. An extension study (A031-06) was also initiated in Canada for boys who participated in the A031-03 study.
    During the course of clinical trials in healthy adults and in DMD boys, some participants experienced minor nosebleeds, gum bleeding, and/or small dilated blood vessels within the skin. These events all resolved fully upon discontinuation of treatment. By themselves, the minor bleeding events and dilated blood vessels were not considered to be a serious safety concern for study subjects. However, based on review of these safety data with the FDA and Health Canada, Acceleron has terminated the A031-03 DMD study and has suspended enrollment and dosing in the follow-on extension study. Pending further analysis of safety data and discussion with health authorities, a new ACE-031 trial for DMD will be planned.

  2. #2
    Rising Chem Guru SwoleChamp's Avatar
    Join Date
    Jul 2010
    Posts
    3,132
    Rep Power
    1490291

    Default

    nice post bro!

  3. #3
    GYM RAT I Eat Therefore I Am's Avatar
    Join Date
    May 2011
    Location
    DFW
    Posts
    341
    Rep Power
    25620

    Default

    Is ACE-031 specific to skeletal muscle? That's one thing about follistatin; they clame to have altered it to only affect skeletal muscle.

    Do you know what journals I can find these studies is?

  4. #4
    Rising Chem Guru SwoleChamp's Avatar
    Join Date
    Jul 2010
    Posts
    3,132
    Rep Power
    1490291

    Default

    yes, on the skeletal muscle effect:

    STUDY

  5. #5
    Rising Chem Guru SwoleChamp's Avatar
    Join Date
    Jul 2010
    Posts
    3,132
    Rep Power
    1490291

    Default

    Administration of a soluble activin type IIB receptor promotes skeletal muscle growth independent of fiber type.

    Cadena SM, Tomkinson KN, Monnell TE, Spaits MS, Kumar R, Underwood KW, Pearsall RS, Lachey JL.
    Source

    Acceleron Pharma Inc., 128 Sidney St., Cambridge, MA 02139, USA.

    Comment in

    J Appl Physiol. 2010 Sep;109(3):621-2.
    Abstract

    This is the first report that inhibition of negative regulators of skeletal muscle by a soluble form of activin type IIB receptor (ACE-031) increases muscle mass independent of fiber-type expression. This finding is distinct from the effects of selective pharmacological inhibition of myostatin (GDF-8), which predominantly targets type II fibers. In our study 8-wk-old C57BL/6 mice were treated with ACE-031 or vehicle control for 28 days. By the end of treatment, mean body weight of the ACE-031 group was 16% greater than that of the control group, and wet weights of soleus, plantaris, gastrocnemius, and extensor digitorum longus muscles increased by 33, 44, 46 and 26%, respectively (P<0.05). Soleus fiber-type distribution was unchanged with ACE-031 administration, and mean fiber cross-sectional area increased by 22 and 28% (P<0.05) in type I and II fibers, respectively. In the plantaris, a predominantly type II fiber muscle, mean fiber cross-sectional area increased by 57% with ACE-031 treatment. Analysis of myosin heavy chain (MHC) isoform transcripts by real-time PCR indicated no change in transcript levels in the soleus, but a decline in MHC I and IIa in the plantaris. In contrast, electrophoretic separation of total soleus and plantaris protein indicated that there was no change in the proportion of MHC isoforms in either muscle. Thus these data provide optimism that ACE-031 may be a viable therapeutic in the treatment of musculoskeletal diseases. Future studies should be undertaken to confirm that the observed effects are not age dependent or due to the relatively short study duration.

    PMCID: PMC2944638
    Free PMC Article
    PMID:
    20466801
    [PubMed - indexed for MEDLINE]

  6. #6
    Future Sexy Campeon
    Join Date
    Dec 2010
    Posts
    1,721
    Rep Power
    0

    Default

    Clinical Results – Recently, Acceleron completed a clinical study of ACE-031 in healthy volunteers. These subjects received a single dose of ACE-031 across a range of dose levels. At higher doses, the effects of ACE-031 on skeletal muscle were encouraging. After a single dose of ACE-031, subjects developed roughly 1 kilogram (over 2 pounds) of muscle at 2 weeks. Moreover, ACE-031 was well-tolerated at all dose levels, with only mild or transient side effects observed.

    Effects of Single-Dose Treatment of ACE-031 on Lean Mass (Human)
    Acceleron is developing ACE-031 for the treatment of patients with neuromuscular diseases, such as Duchenne Muscular Dystrophy (DMD) and Amyotrophic Lateral Sclerosis (ALS), with the goal of improving strength and preserving physical function. By affecting the muscle directly, ACE-031 may one day offer hope to patients suffering from these debilitating diseases. References
    A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs, Mosher DS et al. PLoS Genet 3(5): e79, 2007.
    Regulation of muscle growth by multiple ligands signaling through activin type II receptors, Lee SJ et. al., PNAS 102:18117-18122, 2005.
    Inhibition of myostatin in adult mice increases skeletal muscle mass and strength, Whittemore LA et al., Biochem Biophys Res Commun. 2003 Jan 24;300(4):965-71.
    Regulation of myostatin activity and muscle growth, Lee SJ et. al., PNAS, 98:9306-9311, 2001.

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •  

X vBulletin 4.2.3 Debug Information

  • Page Generation 0.29990 seconds
  • Memory Usage 6,966KB
  • Queries Executed 27 (?)
More Information
Template Usage (39):
  • (1)SHOWTHREAD
  • (1)ad_footer_end
  • (1)ad_footer_start
  • (1)ad_global_above_footer
  • (1)ad_global_below_navbar
  • (1)ad_global_header1
  • (1)ad_global_header2
  • (1)ad_navbar_below
  • (1)ad_showthread_firstpost_sig
  • (1)ad_showthread_firstpost_start
  • (1)ad_thread_first_post_content
  • (1)ad_thread_last_post_content
  • (4)block_html
  • (1)block_threads
  • (1)facebook_footer
  • (1)facebook_header
  • (1)facebook_likebutton
  • (1)facebook_opengraph
  • (1)footer
  • (1)forumjump
  • (1)forumrules
  • (1)gobutton
  • (1)header
  • (1)headinclude
  • (1)headinclude_bottom
  • (6)memberaction_dropdown
  • (1)navbar
  • (5)navbar_link
  • (1)navbar_noticebit
  • (1)navbar_tabs
  • (3)option
  • (6)postbit_legacy
  • (6)postbit_onlinestatus
  • (6)postbit_wrapper
  • (3)showthread_bookmarksite
  • (1)sidebarext_temp
  • (1)spacer_close
  • (1)spacer_open
  • (1)tagbit_wrapper 

Phrase Groups Available (6):
  • global
  • inlinemod
  • postbit
  • posting
  • reputationlevel
  • showthread
Included Files (37):
  • ./showthread.php
  • ./global.php
  • ./includes/class_bootstrap.php
  • ./includes/init.php
  • ./includes/class_core.php
  • ./includes/config.php
  • ./includes/functions.php
  • ./includes/functions_navigation.php
  • ./includes/class_friendly_url.php
  • ./includes/class_hook.php
  • ./includes/class_bootstrap_framework.php
  • ./vb/vb.php
  • ./vb/phrase.php
  • ./includes/class_facebook.php
  • ./includes/facebook/facebook.php
  • ./includes/facebook/base_facebook.php
  • ./includes/functions_facebook.php
  • ./includes/functions_bigthree.php
  • ./includes/class_postbit.php
  • ./includes/class_bbcode.php
  • ./includes/functions_reputation.php
  • ./includes/class_block.php
  • ./includes/block/html.php
  • ./vb/context.php
  • ./vb/cache.php
  • ./vb/cache/db.php
  • ./vb/cache/observer/db.php
  • ./vb/cache/observer.php
  • ./includes/functions_notice.php
  • ./includes/block/threads.php
  • ./packages/vbattach/attach.php
  • ./vb/types.php
  • ./packages/skimlinks/hooks/postbit_display_complete.php
  • ./packages/skimlinks/hooks/showthread_complete.php
  • ./mobiquo/smartbanner.php
  • ./mobiquo/include/classTTConnection.php
  • ./mobiquo/smartbanner/head.inc.php 

Hooks Called (77):
  • init_startup
  • database_pre_fetch_array
  • database_post_fetch_array
  • friendlyurl_resolve_class
  • global_bootstrap_init_start
  • global_bootstrap_init_complete
  • cache_permissions
  • fetch_postinfo_query
  • fetch_postinfo
  • fetch_threadinfo_query
  • fetch_threadinfo
  • fetch_foruminfo
  • load_show_variables
  • load_forum_show_variables
  • global_state_check
  • global_bootstrap_complete
  • global_start
  • style_fetch
  • global_setup_complete
  • showthread_start
  • cache_templates
  • cache_templates_process
  • template_register_var
  • template_render_output
  • fetch_template_start
  • fetch_template_complete
  • friendlyurl_clean_fragment
  • friendlyurl_geturl
  • fb_canonical_url
  • fb_opengraph_array
  • parse_templates
  • fetch_musername
  • notices_check_start
  • notices_noticebit
  • process_templates_complete
  • showthread_getinfo
  • strip_bbcode
  • forumjump
  • friendlyurl_redirect_canonical
  • showthread_post_start
  • showthread_query_postids
  • showthread_query
  • bbcode_fetch_tags
  • bbcode_create
  • showthread_postbit_create
  • postbit_factory
  • postbit_display_start
  • reputation_power
  • reputation_image
  • postbit_imicons
  • bbcode_parse_start
  • bbcode_parse_complete_precache
  • bbcode_img_match
  • bbcode_parse_complete
  • postbit_display_complete
  • memberaction_dropdown
  • tag_fetchbit_complete
  • forumrules
  • showthread_bookmarkbit
  • navbits
  • navbits_complete
  • build_navigation_data
  • build_navigation_array
  • check_navigation_permission
  • process_navigation_links_start
  • process_navigation_links_complete
  • set_navigation_menu_element
  • build_navigation_menudata
  • build_navigation_listdata
  • build_navigation_list
  • set_navigation_tab_main
  • set_navigation_tab_fallback
  • navigation_tab_complete
  • fb_publish_checkbox
  • fb_like_button
  • showthread_complete
  • page_templates