MDRNA Announces Combinations of UsiRNAs in DiLA2 Show Improved Efficacy in Bladder Cancer Model
News Apr 29, 2010
MDRNA, Inc. has reported data demonstrating greater efficacy in tumor reduction in an orthotopic model of bladder cancer with multiple combinations of two UsiRNAs as compared to single target therapy.
The data were presented by Michael V. Templin, Ph.D., Senior Vice President of Preclinical Development at MDRNA, Inc., at TIDES Oligonucleotide and Peptide® Technology and Product Development/IBC's 2nd Annual Oligonucleotide Therapeutic Discovery April 25-28, 2010 in Boston, MA.
Fibroblast Growth Factor 3 (FGFR3), HRAS and Polo-Like Kinase 1 (PLK-1) were selected based on their known molecular alterations in bladder cancer and key roles in cancer cell progression. FGFR3 and HRAS are overexpressed in non-muscle invasive bladder cancer and play a role in tumor recurrence.
Survivin, a protein involved in cell division and inhibition of apoptosis, is associated with tumor pathology, and its over-expression is associated with more serious tumor classifications and therefore the potential for more severe disease. PLK1, a protein involved in cell division and tumor progression, has been shown to play a role in cell proliferation in several cancer types. The diversity in these, as well as other genes identified in bladder cancer highlights the underlying heterogeneity of cancer in general, and supports the importance of a combination approach to inhibit critical targets. MDRNA has developed highly potent UsiRNAs for each of these targets.
To assess the impact of a multi-target approach on tumor growth in vivo, a survivin UsiRNA was paired with FGFR3, HRAS, or PLK1 UsiRNAs and compared to the survivin UsiRNA alone. All UsiRNAs were encapsulated in the Company's proprietary DiLA2-based formulation, and delivered directly to the bladder (intravesical) in an orthotopic cancer model.
For the survivin/PLK1 combination, tumor bioluminescence and survivin mRNA expression was notably lower (~30% for each endpoint) when compared to a survivin alone. Similar results for tumor bioluminescence and mRNA were found with the survivin/FGFR3 combination. With survivin/HRAS there was a ~40% greater decrease in tumor bioluminescence and ~50% greater inhibition of survivin mRNA.