ACE-083 is an experimental drug being developed by Acceleron Pharma for the treatment of muscle weakness in patients with Charcot-Marie-Tooth (CMT) and facioscapulohumeral muscular dystrophy (FSHD).

Neither disease currently has a cure or a treatment approved by the U.S. Food and Drug Administration (FDA) to slow the progression of symptoms, which eventually become debilitating. The goal of ACE-083-treatment is to increase muscle strength and function to improve the overall quality of life of patients.

How ACE-083 works

ACE-083 works by blocking the actions of members of the TGF-beta family of proteins, which are naturally occurring proteins that inhibit muscle growth. In healthy people, TGF-beta proteins are beneficial because they regulate muscle growth and keep them from getting too big. However, in people who have lost muscle mass due to diseases such as CMT and FSHD, inhibition of muscle growth is not helpful.

ACE-083 differs from other drugs that block muscle growth inhibitors in two ways. First, it targets a number of different types of TGF-beta proteins, while other drugs target only one member of the family. Second, it is injected directly into the weak muscles, which reduces the risk of side effects.

ACE-083 in clinical trials

The first clinical trial of ACE-083 (NCT02257489) was a Phase 1 randomized, placebo-controlled study to evaluate the safety and efficacy of ACE-083 in healthy volunteers. The results were promising, with muscle volume increasing by nearly 15 percent at the highest dose. The drug was also well-tolerated. Based on these positive results, Acceleron advanced to the Phase 2 trial phase.

A Phase 2 trial (NCT03124459) evaluates the safety and effectiveness of ACE-083 in patients with weak muscles due to CMT. In Part 1 of the trial, up to 18 adult patients with CMT will receive injections of ACE-083 into the shin muscle once every three weeks for up to five doses.

Analysis of the results of Part 1 will determine the optimal dose to be used in Part 2, which will include up to 24 patients who will be randomized to receive either ACE-083 or a placebo. Participants in Part 2 will also receive injections in the shin muscle once every three weeks for up to five doses.

The primary measure of efficacy will be the change in volume of the shin muscle, as determined by magnetic resonance imaging (MRI). Other measures will include changes in muscle strength and function and quality of life. The trial is expected to be completed by 2019 and is still recruiting participants.


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