By Travis DeGraff

ACE-031

Despite the extremely impressive pictures of myostatin deficient animals, humans have yet to successfully find something that inhibits myostatin to a degree that effectively gives them larger muscle mass.  Follistatin is perhaps the most popular in the bodybuilding world.  However real world results seem lackluster, whether it be the quality of the actual follistatin on the market, or just the simple fact that it may not work in otherwise healthy males.  The more we learn about myostatin the more we learn that it is a complicated process.  And simply inhibiting myostatin may not be the optimal solution to gains.

A slightly more interesting “myostatin inhibitor” is ACE-031, which is a soluble form of activin type IIB receptor.   For example, when they gave already myostatin deficient mice ACE-031 they got even bigger than just myostatin deficient mice [Ref 1].  What this means is that myostatin is not the only regulator of muscle growth.  And ACE-031 seems to be activating (or inactivating) regulators of muscle growth in addition to myostatin inhibition.

This very unique aspect of ACE-031 is its ability to target those multiple hypertrophic pathways is consistent muscle growth.  What I mean by consistent muscle growth is equal growth of both Type I (“slow twitch”) and Type II (“fast twitch”) muscle fiber.  Unfortunately with myostatin inhibition (from follistatin) only Type II muscle fibers seem to grow.  As a weightlifter this might sound great, but excessive Type II muscle fiber has been linked to poor insulin sensitivity and obesity.  So those myostatin deficient animals you see might be strong, but in general their muscular endurance is extremely lacking.

ACE-031 unfortunately is not easy to develop.  And the pharma company Acceleron originally developing it formed a deal with an Irish company called Shire.  By getting Shire’s money (45 million up front) they were able to begin pre-clinical testing on the drug, but they gave up rights to sell it overseas if it ever made it to market.   The first human study gave women one subcutaneous shot of 3 mg’s per kilogram of ACE-031 [Ref 2].  29 days later they found lean body mass increased over 3%, and thigh muscle increased over 5%.  Those are pretty significant results from just one 3 mg/kg shot (or about 270mg’s for a 200lb male).

So what was next?  Well unfortunately the next step in this drug’s development was a Phase II dose escalating study on young boys with muscular dystrophy [Ref 3].  I say unfortunately because the boys experienced non-life threatening side effects such as gum and nose bleeding, and violated blood vessels at the skin.  While these were not serious side effects, such problems early in the drug development cycle are not a promising sign when FDA approval is ultimately your goal.  Acceleron and Shire took a step back to try and determine why these side effects were occurring.  Then in 2013 the two decided to end their relationship after additional testing seemed to be disappointing.  And with that, is the end of ACE-031 research.

ACE-083

With ACE-031 out of the picture for the near term, what is bodybuildings next potential super drug?  Enter ACE-083, the newest muscle wasting drug by Acceleron Pharma:

ace-083

ACE-083 works similar to ACE-031, however (and this is the really cool part) ACE-083 is designed to only increase muscle mass in the muscle that is treated.  Meaning it can literally bring up specific muscles, but have no impact on others.  Imagine the possibilities.  Dennis Wolf could fix his calves, Branch Warren could grow some arms, and none of us would have to worry about heart hypertrophy!

Cool shit, but I’m probably getting way ahead of myself.  That’s because the ACE-083 is still very early in development.  In fact thus far only one mouse study has been completed [Ref 4].  Still the mouse study was very interesting.  The study was quite simple, they injected mice with ACE-083 directly into the left gastrocnemius (calf muscle) and compared it to the right gastrocnemius muscle.  A rough estimate of the human equivalent dose is approximately .004 mg’s to 1.2 mg’s per kilogram, or for a 200lb male approximately 360 micrograms (mcg’s) to 108 milligrams (mg’s).  That’s a huge range, but you can see in the following chart significant results were acheived at the second lowest dose.  And at the highest dose, the muscle was nearly twice as large!

ace-083 myostatin

The percentage increase inace-083 muscle growth muscle mass ranged from a 7% increase at the lowest dose, to a 95% increase at the highest dose.  To ensure ACE-083 did not increase the size of other muscles in the body they also weighed and measured the pectoral and femoris muscles of the mice.  They found no abnormal increases in any other muscle than the treated gastroc.  Meaning it worked only in the treated muscle, which was exactly their goal.  Interesting they found that it’s effect was caused by muscle fiber hypertrophy, and there was no evidence of hyperplasia (new muscle cells).

If all this isn’t quite exciting enough for you, take a look at the picture on the right.  In this picture you can see the left gastroc, which was injected with ACE-083 is almost twice the size of the right gastroc.  This is really quite amazing.

At this point I do not know of any research chemical company selling ACE-083, and I’d imagine this is not something a Chinese supplier could easily manufacture.  So it may be years before we ever see this on the black market.  In the mean time, Acceleron is continuing to prepare for the start of Phase I clinical research with ACE-083.  In their most recent quarterly report they indicated the trials would begin in 2014.   Hopefully, unlike ACE-031, ACE-083 makes progress with more human research.  Drugs like this can not only save lives, but almost always catch the interest of the bodybuilding world (however vain that may be).

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