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Tag Archives: rapamycin

Friday Science Review: June 4, 2010

New fixes for spinal injury, Staph infection and cancers…

Spinal Cord Self-Repair: A natural repair mechanism in our bodies may be the key to treating spinal-cord injuries.  Following a spinal cord injury, there is an increase in expression of serotonin receptors and the receptors are spontaneously active even in the absence of serotonin.  This autoactivation is thought to be a response or repair mechanism that is initiated as a result of the injury.  Pharmacological agents may be used to try to enhance this receptor activity to promote recovery.  The caveat, however, is that the receptors remain “on” and may explain the spasms experienced by spinal injury patients.  In this case, inhibitory drugs may be beneficial to preventing these muscle spasms.  Dr. Karim Fouad and his team conducted the research at the University of Alberta (Edmonton) and present their work in Nature Medicine.

Super Bug’s Magic Revealed:  MRSA, or methicillin-resistant Staphylococcus aureus, is a strain of Staph that has become resistant to most types of antibiotics.  Scientists now know why and what makes a harmless bacteria become pathogenic Super Bugs.  A small chemical (aureusimines) made by MRSA bugs is the key factor that determines their virulence and ability to cause severe disease.  The researchers discovered how these chemicals are made in the bacterium and then tried to shut off the different pathways involved in the synthesis of these chemicals.   Blocking aureusimine production resulted in a much weaker and less virulent bug, which allowed the mouse model patients to recover from S. aureus infections.  This information comes at a crucial time when drug resistance is on the rise and new anti-bacterial targets are desperately needed.  McMaster University scientists led by Dr. Nathan Magarvey describe their breakthrough discovery in the latest Science magazine.

Controlling Cell Growth: The research of Dr. Nahaum Sonenberg and his McGill University team on the mechanisms controlling cell growth and proliferation have had significant impact in advancing the field.  They continue their key discoveries with the delineation of mTORC1 and the 4E-BP proteins.  Although mTORC1 is known to be involved in connecting growth and nutrient signals to control cell size and cell division, 4E-BPs are only involved in mediating the cell proliferation pathway and not cell growth.  This distinction is important because mTORC1 is implicated in a variety of diseases and these related pathways are targets for therapeutic drugs, so further refinements can be made accordingly.  The report is published here in Science magazine.

A Cancer Cure in Sponge? A peptide found in sea sponge can inhibit tumour cell metastasis.  The Neopetrosiamide A (NeoA) peptide prevents tumour cells from sticking to surfaces by decreasing cell surface proteins such as integrins and inducing the disassembly of structural complexes called focal adhesions.  Its mechanism of action is unknown but it somehow causes important “sticky” proteins to be kicked out of the cell rather than trafficking to their proper locations.  This is a developing story to keep an eye on.  The study is published in PLoS One by Dr. Calvin Roskelley’s team at the University of British Columbia.

Friday Science Review: January 22, 2010

Some really exciting research in this week’s review…

Special (RNAi) Delivery: One of the obstacles for RNAi based therapeutics is the difficulty in getting the RNAi into the cells efficiently to invoke a positive response.  Vancouver based Tekmira Pharmaceuticals (TSX: TKM.TO), in partnership with Alnylam Pharmaceuticals (Nasdaq: ALNY) and researchers at the University of British Columbia, Drs. Pieter Cullis and Marco Ciufolini, developed a new and improved RNAi delivery method that is 10X better than their standard delivery platform.  Using their knowledge of lipid structure and how specific features influences delivery into cells, they used a rational design approach to develop a new cationic lipid, DLin-KC2-DMA (KC2), that is used with their current SNALP system (stable nucleic acid-lipid particles) to achieve the remarkable results.  Details of the study are reported in this week’s issue of Nature Biotechnology.

Resolving Stem Cell Populations: The differentiation of stem cells is a complex multi-step process that is not fully understood.   With each step, the potential of that stem cell becomes more and more restricted.  Researchers performed a series of intricate detailed studies on cell populations to resolve distinct Intermediate Term Reconstituting Hematopoietic Stem Cells or ITRC (versus long- and short-term populations).  The significance of this key finding is that researchers who are interested in harnessing the potential of long-term reconstituting hematopoietic stem cells can more accurately study a pure population of true, self-renewing stem cells with homogeneous characteristics.  Prior to this new “intermediate-term” identification, the majority of “long-term” cells were actually comprised of intermediate-term cells.  Dr. Norman Iscove and his team at the University Health Network describe their work in the latest issue of Cell Stem Cell.

Fishing for New Drugs: A high-throughput behavioural monitoring system to observe the response of Zebrafish to neuroactive chemical compounds should help expedite the discovery of new drugs for neurological disorders.  Researchers setup a video system and applied “behavioural barcodes” that they say can track the effects of 14,000 chemicals on zebrafish behaviour.  The capacity of this large-scale screen is unique and the use of zebrafish is quite informative because they are transparent, genetically tractable, and more similar to humans than you might think.  In this platform, response to two strong light pulses after exposure to chemicals is monitored and the observations are translated into barcodes that make data analysis of this magnitude a lot more manageable.  Drs. Jennifer Bryan and Rick White at UBC collaborated with Harvard researchers and published their study in Nature Chemical Biology.

Intrinsic Stimulator of Muscle Regeneration: A new subpopulation of cells in muscle tissue that contribute to muscle injury repair has been identified.  The surprise is that these cells, called fibro/adipogenic progenitors (FAPs), are derived from a different developmental lineage as muscle cells.  These fat-lineage cells, which are resident in muscle tissue, are ‘activated’ in response to muscle damage but they do not become muscle cells.  Instead, they release factors that promote and enhance muscle progenitors in the myogenesis repair process.  The conundrum, however, is that too much of these FAPs can lead to fibrosis and contribute to muscle disorders.  The study, reported in Nature Cell Biology, was led by Dr. Fabio Rossi at the University of British Columbia.

Pharmacoviral Therapy for Gliomas: Oncolytic viruses (VSVs) are used in the treatment against malignant gliomas but are limited in efficacy due to the viral induced IFN (interferon) response – one of our body’s natural defense mechanism.  Knowledge of the molecular mechanisms involving the mTOR pathway in IFN production led researchers to investigate the use of rapamycin, an mTOR inhibitor, in conjunction with the VSVs.  This “pharmacoviral” combinatorial approach was very successful when tested in rats with malignant gliomas and represents a potentially new therapeutic strategy.  Dr. Nahum Sonenberg and his team at McGill University are experts in the mTOR pathway and describe their work in the Proceedings of the National Academy of Sciences.

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