Publications by authors named "Lee Barman"

2 Publications

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Detection of glucocorticoid-like activity in traditional Chinese medicine used for the treatment of Duchenne muscular dystrophy.

Neuromuscul Disord 2003 Nov;13(9):699-704

MyoContract Ltd., Hammerstrasse 25, CH-4410, Liestal, Switzerland

Anecdotal reports of positive influence of certain traditional Chinese medicines on the progression of neuromuscular diseases in general and Duchenne muscular dystrophy (DMD) in particular has raised interest in patient support groups and clinical experts alike. However, clinical signs of steroid-specific side effects in patients treated with a particular form of Chinese medicine raised the concern that they may contain glucocorticoids, which in turn could also explain the mild beneficial effects seen in some of the patients. We have extracted and fractionated capsules containing pulverized Chinese medicine that had been used for the treatment of DMD patients and analyzed their content for glucocorticoid-like activity using promoter-reporter assays. We demonstrate that extracts from this Chinese medicine activate a prototype glucocorticoid-response element, increase the level of utrophin protein in human muscle cells and activate the utrophin promoter A. Based on our bioassays we conclude that this particular Chinese medicine used for the treatment of muscular dystrophy patients contains glucocorticoids as one of its active ingredients.
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http://dx.doi.org/10.1016/s0960-8966(03)00117-2DOI Listing
November 2003

Glucocorticoid-mediated regulation of utrophin levels in human muscle fibers.

Neuromuscul Disord 2002 Oct;12 Suppl 1:S95-104

MyoContract Pharmaceutical Research Ltd., Klingelbergstrasse 70, CH-4056 Basel, Switzerland.

Previous studies on transgenic mice indicate that upregulation of utrophin protein may offer a potential treatment strategy for Duchenne muscular dystrophy. We have analyzed the effect of the glucocorticoid 6alpha-methylprednisolone-21 sodium succinate on utrophin protein levels, using a cell-based assay with differentiated human myotubes, derived from biopsies of healthy individuals or Duchenne muscular dystrophy patients. We found that within 5-7 days 6alpha-methylprednisolone-21 sodium succinate increases utrophin protein up to approximately 40% in both normal and dystrophin-deficient myotubes compared to untreated control cultures. When analyzed in promoter-reporter assays 6alpha-methylprednisolone-21 sodium succinate activated a utrophin promoter A-fragment but did not activate a utrophin promoter B-fragment. Surprisingly, endogenous levels of utrophin mRNA in 6alpha-methylprednisolone-21 sodium succinate-treated muscle cells were unaltered indicating that the utrophin-inducing effect of glucocorticoids may be a result of post-transcriptional mechanisms. We have also analyzed 66 glucocorticoids for their effect on utrophin protein levels and found that glucocorticoids in general are able to induce utrophin protein in human myotubes.
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http://dx.doi.org/10.1016/s0960-8966(02)00089-5DOI Listing
October 2002