The Muscular Dystrophy Association has awarded $120,000 to Cambridge, Mass.-based Catabasis Pharmaceuticals as part of a strategic partnership under which the pharmaceuticals company will test two compounds called CAT-1004 and CAT-1040 in the mdx research mouse model of Duchenne muscular dystrophy (DMD).
The award was made through MDA Venture Philanthropy (MVP), the drug development arm of MDA's translational research program.
"MDA is pleased to support further testing of CAT-1004 to assess the compound's ability to counter muscle-damaging inflammation and support muscle regeneration," said Jane Larkindale, MDA director of translational research. "We're excited to help determine if this compound, or if the related compound CAT-1040, will be helpful in Duchenne muscular dystrophy — and, perhaps, for other diseases in MDA's program."
In 2009, MDA funded Catabasis to complete short term animal studies of anti-inflammatory compounds that act similarly to corticosteroid medications (like prednisone and prednisolone) but with fewer side effects. The orally available, anti-inflammatory agent CAT-1004 was shown to work better than the corticosteroid prednisolone. It worked as well as prednisolone at reducing muscle inflammation, without the prednisolone side effect of reduced muscle weight.
Mice treated with the compound had the same or fewer degenerating muscle fibers than those treated with prednisolone, and had increased numbers of regenerating muscle fibers while those treated with prednisolone had decreased numbers of regenerating fibers.
Catabasis plans to demonstrate in the new four-month study that CAT-1004 reduces inflammation in muscle tissue and improves muscle function. It will compare CAT-1004, CAT-1040 and prednisolone to see which is the most effective compound. If favorable results are obtained, the company plans to begin clinical trials in people with DMD.
Catabasis has completed a safety, tolerability and pharmacokinetics (what the body does to a drug) study of CAT-1004 in healthy human volunteers over an eight-week trial period. It has an open Investigational New Drug application for the compound with the U.S. Food and Drug Administration, which allows it to conduct clinical trials of the investigational drug in the United States.
"We want to thank MDA for this important funding, which validates the preclinical work we have done with CAT-1004 in DMD mouse models," said Michael Jirousek, co-founder and chief scientific officer of Catabasis."The short-term preclinical findings in DMD models are very encouraging, and we look forward to conducting this longer-term study with both CAT-1004 and CAT-1040.
"There is a significant need for new treatment options with improved safety and efficacy for people with DMD. If the preclinical findings prove positive, we will initiate a clinical trial in patients with the disease, which could potentially lead to a new treatment and approach to slow the rate of muscle degeneration in young boys living with DMD."
DMD is a degenerative muscle disease, affecting boys almost exclusively, that involves progressive degeneration of voluntary and cardiac muscles, with resulting weakness and heart abnormalities.
Several studies have shown that corticosteroid medications, such as prednisolone and prednisone, and deflazacort (available in Canada and other countries, but not in the United States), prolong muscle function in DMD. But the mechanism by which they do so remains unclear, and the side effects of these drugs — including weight gain, slowed growth, decreased bone density, behavioral changes, high blood pressure and high blood sugar — can be a barrier to their use.
Despite any drawbacks, corticosteroid medications have been widely used to treat DMD since the 1990s.
In 2005, the American Academy of Neurology (AAN) published guidelines for corticosteroid use in DMD. For more about corticosteroids in in DMD, see the following stories from Quest, May-June 2007:
Corticosteroid medications slow the progression of muscle weakness and prolong walking in children with DMD. However, side effects limit their usage.
If test results are favorable, CAT-1004 or CAT-1040 may be developed into a treatment that will provide the benefits of corticosteroids to people with DMD, without the unwanted side effects.