Research Points to New Directions In Inclusion-Body Myositis Treatment

by Margaret Wahl on September 1, 2007 - 9:47pm

QUEST Vol. 14, No. 5

Inclusion-body myositis (IBM) is a type of muscle disease that’s thought to be part inflammatory (related to immune system activity that causes inflammation) and part degenerative. It’s usually not genetic, but there are genetic forms. The name “inclusion body” comes from clusters of abnormal proteins inside bubble-like spaces in muscle fibers. It doesn’t respond to standard treatments that are effective in other types of myositis.

Caught in the crossfire?

Viruses, specifically a type known as retroviruses, may underlie at least some cases of nongenetic (“sporadic”) IBM, according to Marinos Dalakas at the National Institutes of Health and colleagues.

This research group, which published its findings in the May issue of Annals of Neurology, proposes that a retrovirus may trigger an immune response in the body that’s then misdirected at muscle tissue. They didn’t find viruses inside muscle cells, but they did find them in nearby immune system cells.

So far, they’ve seen nine patients with IBM who also have human immunodeficiency virus or human T-lymphocyte virus 1, and they say they don’t think the association is just a coincidence.

Dalakas’ group has found in a separate study that the drug alemtuzumab (Campath), an immune system suppressant that’s now used to treat a form of chronic leukemia, may have promise for treating IBM.

Valerie Askanas
MDA grantee Valerie Askanas has been working on the toxic buildup aspects of IBM since the early 1990s.

Toxic buildup

In another set of findings published in the May issue of Annals of Neurology, Christian Munz at Rockefeller University and colleagues, including Dalakas, speculate that a normal cellular system called autophagy (self-digestion) is overwhelmed in people with IBM, contributing to a buildup of abnormal and potentially toxic proteins.

This process normally breaks down and recycles old or defective protein molecules, such as beta-amyloid, an abnormally folded molecule found in excess in IBM-affected muscle cells.

Supporting autophagy might be a treatment avenue, these researchers suggest.

Valerie Askanas at the University of Southern California in Los Angeles has been studying the role of beta-amyloid in IBM, with MDA support, since the early 1990s. Her recent research, published in Neuropathology and Applied Neurobiology in April, suggests that the precursor of a protein called myostatin accumulates in IBM muscle fibers in association with the precursor of beta-amyloid.

Modified cells to the rescue

Jacques Tremblay, at the University of Laval in Quebec City, says he hopes to launch a clinical trial in which genetically modified muscle stem cells will be used to treat people with a genetic form of IBM. Tremblay, who plans to use inactivated lentiviruses to deliver GNE genes to stem cells taken from patients with hereditary IBM, has applied to the regulatory agency Health Canada for permission to conduct the study.

“One of the beauties of this approach is that genetic modification of the cells would be done ex vivo [outside the body],” he says, “so we can verify that they are genetically corrected and not tumor-forming, and so that the patient will not be exposed to the viral vector [transporter].

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