The Cross-Border Biotech Blog

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

Tag Archives: Crohn’s Disease

Friday Science Review: January 29, 2010

A productive week of international collaborations leading to new drugs or targets…

Genetic Map of Yeast: A large-scale, genome-wide interaction map of yeast genes was constructed in an international study.  The extensive network of genetic interactions lays out a functional map of the cell where similar biological processes can be grouped together. Yeast has been studied in the past and present because their molecular signaling is similar to human cells and is easy to manipulate.  The detailed “genetic atlas” in this project, a first for any organism, provides important information to better understand genetic functions in relation to diseases.  Their technique also allowed the scientists to map interactions between genes and chemicals, which will aid in choosing drug targets by predicting the extent of the interaction with other genes and how it may affect the cell.  The multi-national project was led by University of Toronto researchers Drs. Brenda Andrews and Charles Boone.  Details of the yeast map study appear in the prestigious journal, Science.

Mutations in Lymphomas: The identity of new mutations associated with specific types of lymphomas is described in this latest Nature Genetics article.  Sequencing of genes involved in the NF-kappaB signalling pathway led to the identification of recurrent mutations affecting the EZH2 histone methyltransferase enzyme.  The oncogene is the second member of this enzyme group found to be mutated in different types of cancer.  Mutations were found in over 21% of a lymphoma subtype, affecting amino acid Tyrosine 641 that renders the enzyme with lower activity.  Dr. Marco Marra at the Michael Smith Genome Sciences Centre (BC Cancer Agency) conducted the sequencing project.

Stopping Alzheimer’s Disease: Inhibition of ACAT1, an enzyme directly involved in cholesterol metabolism, significantly decreases the accumulation of amyloid plaques when tested in a mouse model of Alzheimer.  To gain deeper knowledge of how this works, researchers deleted the ACAT1 gene in mice predisposed to develop Alzheimer’s disease.  The brains of these mice had fewer amyloid plaques with improved cognitive function.  The key finding is that without ACAT1 function, cholesterol accumulates in a subcellular compartment of the cell where it is converted and no longer available to be involved in amyloid plaque formation.  These data supports the use of ACAT1 inhibitors in the battle against Alzheimer’s disease and lends insight into future improvement.  Dr. Nabil Seidah at the Institut de Recherches Cliniques de Montréal collaborated with researchers in the U.S. and published the study in the Proceedings of the National Academy of Sciences.

New Treatment to Stop Malaria: Two enzymes important to the survival of Plasmodium falciparum, the parasite causing malaria, have been discovered in an international collaboration aimed at stopping the drug-resistant parasite.  Malaria parasites invade red blood cells and digest the proteins for fuel to grow and divide until they burst out of the red blood cell and repeat the process again.  The discovery of the parasitic enzymes, PfA-M1 and PfA-M17, which are keys to the digestive process in red blood cells, was the first step in designing therapeutic drugs.  Building three-dimensional structures of the enzymes was the next step in determining how best to target and inhibit the enzyme.  The study suggests that blocking PfA-M1 and Pfa-M17 would prevent the parasite from feasting on the red blood cell and represents a new wave of promising anti-malarial drugs.  McGill University’s Dr. John Dalton led the international research project and is reported in this week’s The Proceedings of the National Academy of Sciences.

Vitamin D fights Crohn’s Disease: Vitamin D deficiency in individuals may contribute to the development of Crohn’s disease, as suggested in this new research report.  Mismanagement of intestinal bacteria triggers an inflammatory response that develops into the autoimmune disorder.  The action of Vitamin D, as the study suggests, is to directly promote the expression of NOD2, which signals to the body of a microbial invasion.  NOD2 then activates NF-kappaB to induce expression of DEFB2 (defensin beta2), an anti-microbial peptide.  To further support Vitamin D’s role, both DEFB2 and NOD2 have been linked to Crohn’s disease in earlier studies.  This is significant to the management of the disease because Vitamin D deficiency is easy to test for through a simple blood test and Vitamin D supplements (and sunlight!) are readily available.  Dr. John White and his team at McGill University and the Université de Montréal published their study in the Journal of Biological Chemistry.

Friday Science Review: November 20, 2009

Intestinal disease genomics and how hedgehogs cause arthritis…

Genetic Clues to ‘Belly Aches’ in Children: The largest genomic investigation into early onset inflammatory bowel disease (IBD) including Crohn’s disease and ulcerative colitis involved the efforts of an international research team.  In total, genetic information from 3,400 children with IBD and 12,000 healthy children were compared.  This study resulted in the identification of five genetic regions associated with susceptibility to pediatric and adolescent IBD.  The team is now taking a closer look at these regions to try to identify the specific proteins that may explain why or how the disease develops.  Another question that they would like to address is why some individuals develop IBD early whereas others develop it later in life.  Two Toronto researchers, Dr. Anne Griffiths (Sickkids) and Dr. Mark Silverberg (Mount Sinai Hospital), contributed their expertise to the study, which appears in this week’s issue of Nature Genetics.

Colon Cancer Susceptibility Genes: In another intestinal disease research project, scientists noticed that different strains of mice exhibited different levels of resistance or susceptibility to colon cancer induced by a chemical carcinogen.  Using genetic studies, the determining factor was mapped to a specific region in chromosome 3 that they designated as colon cancer susceptibility locus 3 (Ccs3).  Within this region are about 94 known genes and they have identified a subset that are expressed at high levels in the colon.  What is also interesting is that Ccs3 in mice is homologous to regions in human chromosome 1 and 4, which also contain genes known to be associated with inflammatory bowel disease and colorectal cancer.  This mouse model will be a very useful tool for future studies on the pathogenesis of colon cancer.  Dr. Philippe Gros led the research team at McGill University and published the study in the journal Oncogene.

Hedgehogs are Key to Osteoarthritis: An unexpected discovery may hold the key to solving painful osteoarthritic disease.  Elevated expression or activity of a group of proteins called Hedgehog resulted in the development of osteoarthritis in mice.  In simple terms, the balance of this signalling pathway in chondrocyte cells determines whether they go on to make cartilage or bone.  In the animal model of osteoarthritis, Hedgehog levels are high and there is less cartilage being produced from the chrondrocytes.  Obviously, Hedgehog becomes an immediate pharmacologic target for the treatment or prevention of osteoarthritis.  You may find it strange that this study on a disease primarily affecting adults is from The Hospital for Sick Children but it just shows that research is full of surprises and you never know where it may take you!  Dr. Benjamin Alman and his research team reported their study in the online edition of Nature Medicine.

Pathway Signalling Antibody Production: A key signalling pathway required for the efficient production of antibodies was identified recently and verified using knockout mice.  A receptor on T cells called ICOS (Inducible Costimulator) is required for their conversion into a specialized type of T cell called Tfh cells (follicular B helper T cells).  As the name implies, their role is to help B cells make the right antibodies to the target.  Dr. Woong-Kyung Suh’s team at Institut de recherches cliniques de Montréal discovered that ICOS activates an enzyme called phosphoinositide 3-kinase (PI3K), which eventually leads to the release of factors that trigger the formation of Tfh cells.  With this knowledge, researchers may find ways to tweak the system to suppress (in autoimmune disease) or enhance (in infectious disease) antibody production as required.  The study is reported in the Proceedings of the National Academy of Sciences.

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