Research Published in the New England Journal of Medicine Demonstrates Marked and Long-Lasting Antiviral Activity Against HCV for Santaris Pharma A/S’ Miravirsen, the First MicroRNA-Targeted Drug to Enter Clinical Trials
HOERSHOLM, Denmark and SAN DIEGO, March 27, 2013 /PRNewswire/ — Santaris Pharma A/S, a clinical-stage biopharmaceutical company focused on the discovery and development of RNA-targeted therapies, today announced the publication of study results online in the New England Journal of Medicine (NEJM). The publication highlights the potential benefits of miravirsen, a host-targeted, pan-HCV genotype anti-viral agent and the first microRNA-targeted drug to enter clinical trials for the treatment of Hepatitis C virus (HCV). In the study, miravirsen, given as a four-week monotherapy treatment, provided robust dose-dependent antiviral activity with a mean reduction of 2 to 3 logs from baseline in HCV RNA (log10 IU/mL). The effect was sustained well beyond the end of therapy.
Clinical data from the Phase 2a study demonstrated the following:
- Miravirsen was safe, well tolerated and provided prolonged antiviral activity well after the last dose of miravirsen monotherapy (x5 weekly injections)
- There were no signs of viral resistance
- Adverse events were infrequent, mild and did not lead to study drug discontinuation
- There were no dose limiting toxicities or discontinuations due to adverse events
- Miravirsen was associated with dose-dependent reductions in [click to continue…]
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Researchers have identified a microRNA liver gene, miR-27b, which regulates lipid (cholesterol or fat) levels in the blood. This regulator gene controls multiple genes involved in dyslipidemia—abnormal blood cholesterol levels that can contribute to heart disease. Study details published in the February issue of Hepatology, a journal of the American Association for the Study of Liver Diseases (AASLD), describe a new in silico approach to identify the significance of microRNAs in regulating disease-related gene pathways.
The Human Genome Project (HGP) was completed in April, 2003 and the world had a map of the 3 billion DNA letters making up the human genome. One of the HGP leaders was Dr. Francis Collins, currently NIH Director and contributor to the present study. “The HGP provided the basic instruction book for human biology,” explains Dr. Collins. “Further genomic studies, such as the investigation of microRNAs, have built upon the efforts of the HGP to explain how the genome carries out its functions, and helps identify genes involved in the development of disease.”
For the present study, lead author Dr. Kasey Vickers from the NIH/NHLBI Lipoprotein Metabolism Section (presently at Vanderbilt University School of Medicine) and colleagues performed high-throughput small RNA sequencing of mouse liver and detected roughly 150 microRNAs. The team used a novel in silico approach to identify microRNA regulatory hub genes involved in lipid metabolism. In human and mouse livers miR-27b was determined to be the strongest hub with 27 predicted targets.
“We found liver miR-27b levels to be sensitive to high triglycerides (hyperlipidemia) in the blood and liver,” said Dr. Vickers. The team reported a nearly 3-fold increase in miR-27b levels in [click to continue…]
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NOTE: hsa-miR-29c* mentioned in the following paper is the retired name for what is now hsa-miR-29c-5p: http://www.mirbase.org/cgi-bin/mature.pl?mature_acc=MIMAT0004673
PHILADELPHIA and REHOVOT, Israel, Feb. 7, 2013 /PRNewswire/ — Rosetta Genomics Ltd. (NASDAQ: ROSG), a leading developer and provider of microRNA-based molecular diagnostics, today announced that data from a study demonstrating the ability of microRNA expression to serve as a biomarker to predict the progression of bladder urothelial carcinoma were published online in the British Journal of Urology International, in an article entitled, “Predicting progression of bladder urothelial carcinoma using microRNA expression.” The article can be accessed online at http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2012.11748.x/abstract and is expected to be published in the print edition of the British Journal of Urology International.
In the study, formalin-fixed, paraffin-embedded samples of 108 non-muscle invasive (“NMI”) bladder carcinomas, and 29 muscle invasive tumors, were collected and highly specific microRNA expression levels were measured by Rosetta Genomics’ microarray technology. Using micro-dissection, specific tumor microRNAs were chosen to be included in the study in order to avoid background contamination derived from surrounding tissue. The study found that the expression level of one microRNA, miR-29c*, was significantly under-expressed in tumors that progressed and could be used to stratify bladder cancer patients into risk groups.
The study showed that significantly higher expression of miR-29c* was detected in NMI bladder tumors that did not progress compared with lesions that did progress. The lower expression of miR-29c* in patients that later progressed was similar to the expression levels seen in patients with muscle invasive disease.
Prediction of recurrence and progression is currently based upon clinical and pathological factors such as: tumor grade, tumor stage, number of lesions, tumor size, prior recurrence rate and presence of concomitant carcinoma in-situ (“CIS”). These factors are not [click to continue…]
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Scripps Research Institute Scientists Uncover a Previously Unknown Mechanism of Memory Formation
JUPITER, FL, January 30, 2013 – It takes a lot to make a memory. New proteins have to be synthesized, neuron structures altered. While some of these memory-building mechanisms are known, many are not. Some recent studies have indicated that a unique group of molecules called microRNAs, known to control production of proteins in cells, may play a far more important role in memory formation than previously thought.
Now, a new study by scientists on the Florida campus of The Scripps Research Institute has for the first time confirmed a critical role for microRNAs in the development of memory in the part of the brain called the amygdala, which is involved in emotional memory. The new study found that a specific microRNA—miR-182—was deeply involved in memory formation within this brain structure.
“No one had looked at the role of microRNAs in amygdala memory,” said Courtney Miller, a TSRI assistant professor who led the study. “And it looks as though miR-182 may be promoting local protein synthesis, helping to support the synapse-specificity of memories.”
In the new study, published in the Journal of Neuroscience, the scientists measured the levels of all known microRNAs following an animal model of learning. A microarray analysis, which enables rapid genetic testing on a large scale, showed that more than half of all known microRNAs are expressed in the amygdala. Seven of those microRNAs increased and 32 decreased when learning occurred.
The study found that, of the microRNAs expressed in the brain, miR-182 had one of the lowest [click to continue…]
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ROSEMONT, Ill., Jan. 28, 2013 /PRNewswire-USNewswire/ — Currently there is no effective treatment used in clinical practice for patients with an injured spinal cord. However, a group of orthopaedic scientists have recently discovered that the administration of microRNA-210 could be an effective treatment for an injured spinal cord by promoting regeneration following injury.
Previously, microRNA-210 has been studied as an effective treatment for cancer and other diseases. Scientists noted that there was an absence of this particular gene in cancerous tumors, but it was found in abundance in healthy tissue. By delivering what was missing directly to the diseased tumor, scientists were able to stop the progression of the disease. Other scientists, however, noted that microRNA has the possibility to actually promote the growth of certain cancers.
Dr. Satoshi Ujigo from Hiroshima University in Japan and his colleagues applied this same theory to injured spinal cords hoping for similar results. His work was recently [click to continue…]
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