welcome..
to the new athlete performance enhancers aka gene doping. This is really really new. They are still doing studies on this and Adults and children with MD. Here is some research on Follistatin and the study done with MYO-029:
March 28, 2008
Myostatin inhibitor update: Boosting follistatin may be better
Wyeth is not stopping developement of drug MYO-029 for blocking myostatin. They foudnd that MYO-029 was safe but that it was not very good at blocking myostatin or boosting muscle growth. They and other companies are working on more powerful and hopefully effective versions.
Two sets of experiments investigating the effects of interfering with myostatin, a protein that limits muscle growth, have shown that this approach may have to be individualized with respect to different types and stages of muscular dystrophy, and that some myostatin suppression strategies may be better than others. Boosting follistatin not only suppresses myostatin but also affects various cell signaling pathways and reduces inflammation. I had previously covered the follistatin gene therapy where it increased muscle size by four times for mice, but that did not describe the differences between the different methods. I have also had extensive coverage of myostatin inhibitors and the safer and more effective increase in muscle mass over high dosage steroids that they represent. Safely increasing muscle mass will not be good for making people stronger it can also help with fat reduction and control (muscle burns more calories) and can help with the health of more frail people (stronger people can stay more mobile and are able to tolerate falls better.
Investigators injected genes for the protein follistatin inside an adeno-associated viral shell into upper and lower leg muscles in 3-week old mice with DMD. Follistatin is known to inhibit myostatin activity. The mice, divided into high-dose and low-dose treatment groups and an untreated (control) group, were then observed for five months.
The mice treated with follistatin genes developed larger bodies and larger, heavier muscles, with the high-dose group showing the greatest effects. Follistatin was detected in the bloodstream of low- and high-dose-treated mice, and it affected muscles far from the injection sites.
The investigators observed an increase in the size of muscle fibers in mice receiving the gene therapy but not in fiber numbers.
Both groups of treated mice showed reduced levels of creatine kinase, indicating less leakiness of muscle-fiber membranes compared to control mice. The researchers speculate that the treated fibers became less susceptible to damage.
The investigators then injected 7-month-old DMD-affected mice with follistatin genes in viral shells. These older mice showed increases in strength about two months after the injections, which persisted for the more than 18 months during which the mice were evaluated.
At the end of the study, the treated mice had substantially fewer groups of dead muscle fibers, fewer inflammatory cells in their muscles, and less scar tissue than did untreated mice, and their muscle fibers were larger in diameter than those of the control group.
The improvements were sustained and well tolerated over more than two years.
Boosting follistatin not only suppresses myostatin but also affects various cell signaling pathways and reduces inflammation.
A phase I/IItrial of MYO-029 in adult subjects with muscular dystrophy.Wagner KR, Fleckenstein JL, Amato AA, Barohn RJ, Bushby K, Escolar DM, Flanigan KM, Pestronk A, Tawil R, Wolfe GI, Eagle M, Florence JM, King WM, Pandya S, Straub V, Juneau P, Meyers K, Csimma C, Araujo T, Allen R, Parsons SA, Wozney JM, Lavallie ER, Mendell JR.
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-7519, USA.
[email protected]
OBJECTIVE: Myostatin is an endogenous negative regulator of muscle growth and a novel target for muscle diseases. We conducted a safety trial of a neutralizing antibody to myostatin, MYO-029, in adult muscular dystrophies (Becker muscular dystrophy, facioscapulohumeral dystrophy, and limb-girdle muscular dystrophy). METHODS: This double-blind, placebo-controlled, multinational, randomized study included 116 subjects divided into sequential dose-escalation cohorts, each receiving MYO-029 or placebo (Cohort 1 at 1 mg/kg; Cohort 2 at 3 mg/kg; Cohort 3 at 10 mg/kg; Cohort 4 at 30 mg/kg). Safety and adverse events were assessed by reported signs and symptoms, as well as by physical examinations, laboratory results, echocardiograms, electrocardiograms, and in subjects with facioscapulohumeral dystrophy, funduscopic and audiometry examinations. Biological activity of MYO-029 was assessed through manual muscle testing, quantitative muscle testing, timed function tests, subject-reported outcomes, magnetic resonance imaging studies, dual-energy radiographic absorptiometry studies, and muscle biopsy. RESULTS: MYO-029 had good safety and tolerability with the exception of cutaneous hypersensitivity at the 10 and 30 mg/kg doses. There were no improvements noted in exploratory end points of muscle strength or function, but the study was not powered to look for efficacy. Importantly, bioactivity of MYO-029 was supported by a trend in a limited number of subjects toward increased muscle size using dual-energy radiographic absorptiometry and muscle histology. INTERPRETATION: This trial supports the hypothesis that systemic administration of myostatin inhibitors provides an adequate safety margin for clinical studies. Further evaluation of more potent myostatin inhibitors for stimulating muscle growth in muscular dystrophy should be considered.
PMID: 18335515 [PubMed - indexed for MEDLINE]
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