The findings of preclinical studies suggest that the M10 peptide may help protect against fibrotic damage in patients with systemic sclerosis, and particularly in those who develop interstitial lung diseases (ILD). The Medical University of South Carolina (MUSC) researchers showed that M10, a ten-amino acid peptide formed from the natural cleavage of the receptor tyrosine kinase MET by the caspase 3, could protect against fibrotic injury in a bleomycin-induced model of ILD. In addition, the showed that its anti-fibrotic effects are likely due to its modulation of the transforming growth factor beta 1 (TGF-?1) pathway.
The MUSC researchers evaluated the ant-fibrotic effects of M10 using a scrambled peptide as a control. A news report from Science Daily indicates that the scrambled peptide had the same ten amino acids as M10 but arranged in a different order, and fibrosis was quantitated using the Ashcroft scale. The results of the study showed that mice receiving bleomycin plus a scrambled peptide showed greater than 8 times more lung fibrosis than controls receiving saline and scrambled peptide. However, the report notes that Ashcroft scores dropped to 1.67±1.01 when mice were administered both bleomycin and M10, suggesting the anti-fibrotic potential of this peptide.
The findings of the study suggest that the anti-fibrotic effects of M10 may rely on its suppression of the TGF-?1 pathway. According to a Science Daily news report, protein interaction assays showed that M10 likely achieves such suppression by interacting with the Smad2 protein, thereby preventing it from binding to Smad3, which is necessary for the downstream inflammatory effects of the TGF-?1 pathway.
Galina S. Bogatkevich, MD, PhD, senior author of the article says, “We observed that treatment with M10 by intraperitoneal injection markedly improved bleomycin-induced lung fibrosis in mice, suggesting that the M10 peptide may have potential for use in the treatment of scleroderma-associated interstitial lung disease and other forms of pulmonary fibrosis, for example, idiopathic pulmonary fibrosis.”
To establish the therapeutic anti-fibrotic efficacy of M10, Bogatkevich and her MUSC colleagues are planning experiments in which M10 will be administered a week after the installation of bleomycin when fibrotic damage has already occurred. If the additional experiments suggest therapeutic efficacy, Bogatkevich hopes to find an industry partner to help move M10 forward into clinical trials.
Photo Credit: Reproduced from Translational Research
Source: Science Daily