ACE-031 (1 MG)

Description

ACE-031 Research and Muscle Protection After Menopause

In a clinical trial using ACE-031, researchers discovered it could be helpful when trying to maintain muscle mass in postmenopausal, healthy women. Muscle maintenance is essential to long-term bone health and reduces the risks of falls and joint injuries in both men and women as they age. In a small placebo-controlled trial, participants receiving ACE-031 experienced significant increases in lean body mass and thigh muscle volume after just one single dose[1]. It was interesting because an unexpected secondary outcome was observed: participants receiving ACE-031 showed improvement in serum biomarkers of both bone and fat metabolism. This suggests that ACE-031 may help inhibit fat storage while also boosting bone production. [1]

ACE-031 May Be Necessary for Maximum Muscle Cell Growth

Studies in mice have shown that maximum muscle growth can only be achieved with a myostatin inhibitor like ACE-031. Furthermore, it appears that blocking myostatin by any number of avenues is most beneficial. These preliminary findings suggest that preventing muscle atrophy in muscle-wasting conditions might require a multifaceted approach utilizing therapies that increase muscle growth (growth hormone, IGF-1) and prevent muscle wasting (ACE-031). [2]

ACE-031 Research and Energy Metabolism

Research has suggested that myostatin inhibited via ACE-031 may lead to elevated serum lactate levels in mice. When myostatin is inhibited, it prevents the negative effects of moderate muscle fatigue. Resistance exercise with a perfect dosage of ACE031 also benefits from the inhibition of myostatin, as it strengthens muscle tissue, helping preserve and grow blood vessels.[3]

ACE-031 Research and Strength

Data generated on mice during testing with ACE-031 suggests that it can improve muscle function. Taking ACE-031 improved force-generating capacity in muscle tissue, partly thanks to preserving energy supply and shifting muscle thermodynamics towards oxidative respiration. In the mice, administration of ACE-031 improves maximum and total contractile force by 40% and 25% respectively. There was no overall change in fatigue of muscle though, indicating that ACE-031 improves muscle strength without affecting energy dynamics. The research revealed no changes in ATP homeostasis or contractile efficiency.[4]

ACE-031 Tested in Clinical Trials for Muscle Repair

Duchenne muscular dystrophy (DMD) is an x-linked recessive condition that is primarily characterized by acute muscle loss. It usually leads to an inability to walk by age 12 with muscles that lacks protein content but are exceptionally high in fat content. Due to a dysfunctional dystrophin protein, muscle cells in DMD are usually weak and decumbent to damage. Even though this is the primary cause of the disease, a secondary effect do occurs when myostatin leaks from damaged muscle cells and slows or inhibits growth in other cells. Gene therapy for myostatin deficiency has yet to be successful, but research on ACE031 is proving promising. In a recent clinical trial, ACE-031 resulted in a trend toward improved muscle function. The peptide improved lean body mass and bone density while reducing fat mass. These results correlate with studies of ACE-031 that suggest it may have positive effects on bone and fat metabolism. [5]

ACE-031 Research and Bone Density

In a mouse model of DMD, ACE-031 was administered just once per week for seven weeks. As the trial ended, the mice receiving dosage of ACE031 had been noticed to have significant growth in terms of total body and muscle weight as well as in bone mineral density. Increase in bone mineral density appears to be a result of decreased numbers of osteoclasts (cells responsible for bone loss). The increased mass wasn’t only incidental either, strength testing shows that the enhanced mineralization substantially improved the biomechanics of the bone and increased both the maximum force the bones could tolerate as well as the stiffness of the bones[6]. 

Even though the trial was designed to investigate muscle effects of ACE031 and yielded very positive results in this primary research, the team was smart to follow up on the observed bone effects as well. This trial showcases that ACE-031 increased bone mass by nearly upto 30% in the mice. This suggests that it should be explored as a potential treatment for osteoporosis. The fact that it boosts muscle strength and bone density while decreasing fat deposits makes ACE-031 a very tantalizing molecule to explore for treating the physiologic effects of aging.

Cancer Treatment and Muscle Loss

Cancer and chemotherapy are some of the biggest contributors to muscle loss.  Research shows that both activate signaling pathways that lead to the death of muscle cells and necrosis. Both conditions also tend to changes in oxidative respiration, which puts metabolic stress on muscles.  These negative effects are in addition to the increased production of free radicals that both cancer and chemotherapy cause (an indirect cause of muscle damage).

Treatment with ACE-031 prevents activation of the ERK1/2 pathway in muscles, which further prevents muscle fiber atrophy via programmed cell death. As discussed above, ACE-031 also safeguards mitochondrial function in muscles and increases fiber energy efficiency in muscle cells. This, of course, helps to mitigate the negative metabolic effects of cancer and chemotherapy by increasing the level of energy usage in a setting of scant nutrition. Improved energy usage also decreases the number of free radicals that are generated during metabolism[8].  Researchers have called for testing ACE-031 in combination with anticancer drugs to determine the degree of effectiveness of the combination in preventing chemo therapy induced muscle atrophy.  It is vital to note as well that a few cancers produce myostatin themselves and that ACE-031 is a potential treatment for preventing muscle wastage in this reference.

Research in cell culture shows that ACE-031 averts muscle cell wasting via myostatin[9].  Cancer cells appear to have many direct/indirect effects on the functioning of muscles, inclusive of deactivation of the natural version of ACE-031 as well as reducing the number of mitochondria (and hence energy production) in muscle cells.  The benefits of ACE-031 in cancer are not strictly relatable to the composition, strength of muscle, and lean body mass. It is evident that reducing muscle damage in the pretext of cancer and cancer treatment delays the life duration in a remarkable manner. In addition to this, deactivating myostatin in the setting of cancer increases the sensitivity of insulin, decreases fat deposition (lipodystrophy), reduces inflammation, and boosts both bone strength and rates of healing following fracture[10].

Article Author

The above literature was researched, edited and organized by Dr. Logan, M.D. Dr. Logan holds a doctorate degree from Case Western Reserve University School of Medicine and a B.S. in molecular biology.

Scientific Journal Author

Dr. Attie joined Acceleron in December 2009, and brings over 20 years of experience in the biotech industry and academic research. Previously, he was at Altus Pharmaceuticals, where he was Vice President of Clinical Development and Medical Affairs. Before that, Dr. Attie was Chief Medical Officer at Insmed, where he was responsible for obtaining FDA approval and commercialization of an IGF-1-related product. Prior to that, Dr.Attie held numerous positions during his 12-year tenure at Genentech, where he was responsible for several phase I-IV studies and participated in 9 FDA submissions for growth hormone. Dr. Attie was Assistant Clinical Professor of Pediatrics at the University of California San Francisco Medical Center, is board-certified in Pediatrics and Pediatric Endocrinology, and has over 40 publications in peer-reviewed journals. He received his M.D. degree from New York University Medical Center and received his B.A. (in Music) from the University of Michigan, Ann Arbor.

Dr. Attie is being referenced as one of the leading scientists involved in the research and development of ACE-031. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between PeptidesforSale.com and this doctor. The purpose of citing the doctor is to acknowledge, recognize, and credit the exhaustive research and development efforts conducted by the scientists studying this peptide. Dr. Attie is listed in [1] under the referenced citations.

Referenced Citations

[1] K. M. Attie et al., “A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers,” Muscle Nerve, vol. 47, no. 3, pp. 416–423, Mar. 2013. [PubMed]

[2] F. Morvan et al., “Blockade of activin type II receptors with a dual anti-ActRIIA/IIB antibody is critical to promote maximal skeletal muscle hypertrophy,” Proc. Natl. Acad. Sci. U. S. A., vol. 114, no. 47, pp. 12448–12453, 21 2017. [PubMed]

[3] K. Relizani et al., “Blockade of ActRIIB signaling triggers muscle fatigability and metabolic myopathy,” Mol. Ther. J. Am. Soc. Gene Ther., vol. 22, no. 8, pp. 1423–1433, Aug. 2014. [PubMed]

[4] N. Béchir et al., “ActRIIB blockade increases force-generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo,” FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol., vol. 30, no. 10, pp. 3551–3562, 2016. [PubMed]

[5] C. Campbell et al., “Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial,” Muscle Nerve, vol. 55, no. 4, pp. 458–464, 2017. [PubMed]

[6] T. Puolakkainen et al., “Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy,” BMC Musculoskelet. Disord., vol. 18, no. 1, p. 20, 19 2017. [NCBI]

[7] P. Bialek et al., “A myostatin and activin decoy receptor enhances bone formation in mice,” Bone, vol. 60, pp. 162–171, Mar. 2014. [PubMed]

[8] R. Barreto, D. L. Waning, H. Gao, Y. Liu, T. A. Zimmers, and A. Bonetto, “Chemotherapy-related cachexia is associated with mitochondrial depletion and the activation of ERK1/2 and p38 MAPKs,” Oncotarget, vol. 7, no. 28, pp. 43442–43460, Jul. 2016. [PubMed]

[9] S. Lokireddy et al., “Myostatin is a novel tumoral factor that induces cancer cachexia,” Biochem. J., vol. 446, no. 1, pp. 23–36, Aug. 2012. [PubMed]

[10] H. Q. Han, X. Zhou, W. E. Mitch, and A. L. Goldberg, “Myostatin/activin pathway antagonism: molecular basis and therapeutic potential,” Int. J. Biochem. Cell Biol., vol. 45, no. 10, pp. 2333–2347, Oct. 2013. [PubMed]