The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Tag Archives: small molecule

Friday Science Review: May 14, 2010

A Cure for Brain Cancer: An aggressive type of brain cancer called glioblastoma may be cured using the small molecule dichloracetate (DCA), a cheap and safe generic compound.  The drug works by altering the metabolism of the cancer cells, which is an emerging concept that exploits the different (higher) energy demand of cancer cells.  DCA’s target in the cells is the metabolic enzyme pyruvate dehydrogenase kinase II and it also promotes cell death in glioblastoma cancer cells and cancer stem cells.  In an 18-month study, some of the five patients’ tumours either regressed in size or did not grow any more.  Drs. Kenn Petruk and Evangelos Michelakis at the University of Alberta describe their study showing efficacy of DCA in humans for the first time in the journal Science Translational Medicine.  It is interesting to note that these and future studies are funded by government grants and private donations since the pharmaceutical industry is not interested in a compound that is readily available and without intellectual property protection (ie. no $cha-ching$).

Embryonic Cells Can Stop Viruses: Embryonic cells have a natural defence mechanism to limit the ability of viruses to express their genes and thereby prevent infection and further spread of the virus.  Researchers also determined that the different layers of cells in the developing embryo have different capacities to silence viral activation.  This “graphical abstract” published in Cell Stem Cell shows the outer layer of extraembryonic endoderm stem cells as the first line of defence with the strongest abilities to extinguish viral gene expression.  Several proteins including chromatin remodelling and repressor complex proteins were also identified to play key roles in this process.  The study was lead by Dr. Mellissa Mann at the University of Western Ontario.

If Only Mice Could Talk: This one is a bit strange.  It looks like mice express pain through facial expressions similar to the way humans do.  McGill University researchers developed the Mouse Grimace Scale to aid scientists working with lab animals to better ‘communicate’ with the animals.  Not only will this help to minimize and manage the stress that is inflicted on the animals but they can read the facial responses to determine whether a drug treatment is working or as an indicator of negative side effects.  Check out the study by Dr. Jeffrey Mogil in the issue of Nature Methods.

Pathogens Are Our Friends: Diphtheria Toxin (DT) is a potent cytotoxin that kills the cells that it binds to.  The DT385 is a recombinant version that is truncated and can be targeted to cancer cells to be used as a therapeutic agent.  In the present study, 15 of the18 human cancer lines tested were inhibited by DT385 as a result of increased apoptosis and decreased protein synthesis.  Dr. David Waisman at Dalhousie University published his study online in PLoS One.  Using pathogen proteins as therapeutic agents is not a new concept.  Oncolytics Biotech’s REOLYSIN® is derived from the Reovirus and Advaxis, Inc. exploits the Listeria bacterium to activate the immune system in an immunotherapy approach.

Studying Herpes Infection: Dr. Karen Mossman (McMaster University) investigated Herpes Simplex Virus-1 infection and how a viral protein, ICP0, is localized properly in the cell to block Interferon Regulatory Factor 3 (IRF3), the cell’s innate antiviral mechanism.  The study is described in PLoS One journal.

Friday Science Review: December 4, 2009

Universal Cancer Signalling Pathway: This is an interesting new twist on cancer signalling that may make scientists rethink how to tackle the disease.  It is thought that there is no single cure for cancer as the hetergenous disease may arise from mutations in a number of different pathways.  In this report, however, researchers demonstrate that many of the cancers converge on HIF-2a, part of the oxygen-sensing system that is required for tumours to grow.  By inhibiting HIF-2a, they could attenuate the growth of a diverse number of aggressive cancers including glioblastomas, colorectal tumours, and non-small cell lung carcinomas.  This universal cancer axis converging on HIF-2a could turn out to be a silver-bullet for cancer therapy.   Dr. Stephen Lee at the University of Ottawa led the team and describes the research in the online edition of the Proceedings of the National Academy of Sciences.

SKP’ing Stem Cells: A special type of cell called SKPs (skin-derived precursors) may be the elusive adult dermal stem cell involved in regenerating skin, wound-healing, and keeping hair healthy and growing.  In the study, researchers characterized the specialized population of cells and determined that SKPs can self-renew, maintain their ability to transform into other cells types, and regenerate hair follicles or other dermal cell types when grafted.  These properties are suggestive that SKPs are indeed THE dermal stem cells and may have important future applications such as in hair restoration and wound-healing.  Dr. Jeffrey Biernaskie completed the research in the lab of Dr. Freda Miller at Sickkids Hospital and recently started his own group at the University of Calgary.  The report appears in this latest edition of Cell Stem Cell.

Comparative Genomics Links Autism and Schizophrenia: A new study comparing the genomes of autistic patients and schizophrenic patients proved the connection between the two disorders that were previously thought to share behavioural similarities.  Both illnesses are associated with anomalies in the same region of the genome but differ substantially in the nature of the genetic changes.  Part of the genomic region is missing in autistic patients whereas extra copies of the genome are present in schizophrenic patients.  The affected genes appear to control head size and brain growth with overdevelopment of the brain in autistic patients and underdevelopment in schizophrenics.  By knowing that the two disorders are genetically linked, research on one disorder immediately provides clues for the other and will aid in advancing treatment options for both.  The study was conducted by Dr. Bernard Crespi’s group at Simon Fraser University and is reported in the Proceedings of the National Academy of Sciences.

Signalling Links in Neurological Disorders: Perturbations in either Dopamine or BDNF (brain-derived nerutrophic factor) pathways are implicated in neurological disorders.  Researchers have now defined the molecular relationship linking the two pathways to similar disorders.  The calcium signalling cascade is the key intermediate between dopamine receptor activation and BDNF production leading to neuronal growth.  With this new understanding of the pathways associated with schizophrenia, depression, and drug addiction, additional molecular targets are available for potential therapeutic intervention.  The study was led by Dr. Susan George at the Centre for Addiction and Mental Health (Toronto) and is reported in the early online edition of the Proceedings of the National Academy of Sciences.

Small Molecule Pathway Database: SMPDB (www.smpdb.ca) is an interactive, visual database containing more than 350 small-molecule pathways found in humans.  It is designed to support drug discovery research and pathway elucidation by employing clinical metabolomics, transcriptomics, proteomics and systems biology information.  The pathways describe relevant organs, organelles, subcellular compartments, protein cofactors, protein locations, metabolite locations, chemical structures and protein quaternary structures.  SMPBP is a very useful tool that was put together by Dr. David Wishart’s group at the University of Alberta and is described in detail in Nucleic Acids Research.

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