The Muscular Dystrophy Association has awarded $1,549,725 to ReveraGen BioPharma, a Rockville, Md., biotechnology company, for development of a dissociative glucocorticoid to treat Duchenne muscular dystrophy (DMD).
The goal is to develop a drug that provides the benefits of currently available glucocorticoids but that doesn't cause the deleterious side effects associated with these medications. (Glucocorticoids are a type of corticosteroid.)
The award was made through MDA Venture Philanthropy (MVP), the drug development arm of MDA's translational research program, in partnership with the U.S. National Institutes of Health Therapeutics for Rare and Neglected Diseases (TRND) program.
Current synthetic glucocorticoids on the market include drugs such as prednisone, prednisolone and deflazacort. These medications, which are derived from the hormone cortisol, have been shown to prolong walking ability and respiratory function, and reduce the need for spinal surgery in DMD. They have therefore been recommended for daily use in this disease by the American Academy of Neurology in 2005 and by the U.S. Centers for Disease Control in 2009.
Glucocorticoids have powerful anti-inflammatory effects, which are thought to be one of the ways in which they sustain muscle health in DMD. They also support cell membrane integrity, another possible therapeutic effect in this disease.
However, at the recommended daily dosages for DMD, long-term use of drugs like prednisone or deflazacort often leads to significant deleterious side effects. These include (but aren't limited to) weight gain, growth arrest, bone fragility, cataracts, high blood pressure and mood changes.
ReveraGen BioPharma (formerly known as Validus BioPharma) has developed an experimental compound called VBP15, which may offer people with DMD the beneficial effects of prednisone and related drugs without the side effects.
The unwanted side effects, ReveraGen scientists have found, are largely due to the genomic mechanism of action in glucocorticoids. VBP15 does not appear to have this genomic mechanism of action, the scientists say, but it appears to retain the beneficial effects of glucocorticoids' nongenomic mechanisms, which are those that combat inflammation and stabilize cell membranes.
ReveraGen says mice with a DMD-like muscle disease benefited from treatment with this drug, showing improved muscle function, increased activity and reduced muscle inflammation.
If VBP15 or a similar compound proves safe and effective in more animal studies, ReveraGen will apply for permission from regulatory agencies to test the drug in humans.
MDA is also funding the development of other anti-inflammatory compounds that may do some of what glucocorticoids do for DMD patients, without the side effects.
The ReveraGen compound, and possibly other experimental anti-inflammatory drugs now in the pipeline, could have implications for other diseases in MDA's program, such as dermatomyositis (DM), polymyositis (PM), myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS). In these disorders, glucocorticoids are frequently used to suppress a misdirected attack by the immune system on muscle and other tissues.
For more on steroid use in DMD and other neuromuscular diseases, see the following stories from Quest, May-June 2007: