making muscle wasting history

When single papers appear about some new drug or treatment for a complex condition such as DMD, one has to have a certain healthy sense of scepticism, however, when two appear from diverse laboratories, one should look at these in more detail. This has happened in the case of a drug, called Imatinib. It was discussed in two recent papers (1,2). At this stage both papers deal only with mdx mice, but the relevance to human DMD should not be understated.
In the first paper from Cleveland, U.S.A. (1), the authors investigated the anti-inflammatory and antifibrotic effects of imatinib in mdx mice. It should be noted, that Imatinib has been approved by the U.S. Food and Drug Administration for treating chronic myelogenous leukemia (CML); gastrointestinal stromal tumors (GIST) as well as a number of other malignancies by blocking certain pathological pathways. Some of these pathways have been implicated in regulating organ fibrosis and inflammation (3). These and other findings suggested to the authors (1), that Imatinib may hold a potential for the treatment of patients with DMD, especially by inhibiting the muscle inflammation and fibrosis, which is associated with DMD.
Their studies, which are beautifully illustrated, showed that Imatinib attenuated the early development of diaphragm fibrosis in mdx mice. It improved hind limb grip strength in mdx mice. After four weeks’ treatment the hind limb grip strength of Imatinib-treated mdx mice was significantly higher than placebo-treated and untreated mdx mice, although it was still lower than wild-type mice. This was maintained after six weeks. Imatinib treatment also inhibited TNF-α and IL-1β gene expression in mdx diaphragm. The detailed biochemical pathways involved in these effects are clearly presented. They conclude that these studies may well provide a steroid-sparing agent and thus ‘broaden therapeutic options for DMD’.
In the second paper (2) a team from São Paulo Brazil, also investigated the extent to which Imatinib mesylate, a derivative of Imatinib as it is currently marketed, might benefit DMD patients by testing it on mdx mice. Again their results are beautifully illustrated and they agree with those of the other study (1). Giving Imatinib mesylate to exercised mdx mice reduced the levels of pro-fibrogenic and pro-inflammatory cytokines. The authors consider that their findings ‘might provide evidence that may be important for modulating immune cell infiltration so as to ameliorate the dystrophic pathology in mdx mice’. The clinical potential for DMD patients of the findings of both these studies is very clear and it should not be forgotten that these are drugs already in approved for human use albeit in other conditions.