The Cross-Border Biotech Blog

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

Tag Archives: regenerative medicine

State of the Biotech Industry — Heading into BioFinance

As the BioFinance conference in Toronto starts up today, I thought it would be worth looking at a few recent data points for the biotech industry:

  • The Q1 Burrill data (via PharmPro) shows above-market gains for public biotechs (up 8% in Q1), $6.1 billion of pharma partnering deals were done, and total biotech VC investments were up 7% in Q1 (over Q4 ’09) though follow-on VC rounds were down 52%.
  • Regenerative medicine company Tengion Inc. is heading for an IPO this week, aiming (low, says John Carroll) for 4.4 million shares at $8 to $10 apiece, with current stockholders taking about $15 million of the offering.  Watch this one for a good barometer of what a clinical stage biotech (lead product in Phase II) can aspire to.
  • Public investment is still running strong in many jurisdictions as well.  Ontario is waiting to learn how MRI’s new money will be spent; Palm Beach Gardens in Florida is setting aside 681 acres for a biotech park; and the Washington DC region continues to invest in its strong cluster, including a new tax law in Virginia that “creates a three-year window under which entrepreneurs and investors can start and invest in early stage technology companies in Virginia without having to pay any long-term capital gains taxes on the returns those companies generate.”

Stay tuned here and @crossborderbio on Twitter for updates from the conference.

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Friday Science Review: February 12, 2010

New Discovery for Neonatal Diabetes: Researchers uncovered an important role for the Rfx6 gene.  Its integrity is required for normal development of the islets of Langerhans cells in the pancreas that produces important hormones including insulin.  Genetic mutations found in Rfx6 are the cause of severe neonatal diabetes where there are no insulin producing islets of Langerhans cells.  To prove the critical role of Rfx6 in directing the differentiation of early pancreatic cells, researchers disrupted the gene in mice and observed the development of an identical disorder as displayed in humans.   Identifying the gene is a key piece of the puzzle and will lead to new avenues to find treatments for all types of diabetes.  Dr. Constantin Polychronakos and his team at McGill University collaborated with researchers from UCSF and report their study in the on-line edition of Nature.

Controlling Stem Cell Fate: A genome-wide screen identified the PCL2 (polycomb-like 2) gene as a key decision maker in determining the fate of stem cells.  This is an important area of research because stem cell based therapies in regenerative medicine are on the rise but more thorough understanding of stem cell control is necessary for safety reasons.  In the absence of PCL2, stem cells can no longer differentiate into specialized cells regardless of adding stimulating factors to try to push it to differentiate.  Once they re-introduced PCL2 into the stem cells, they were able to drive differentiation again.  By mapping the network of genes that PCL2 regulates, they can trace the steps in the path of a stem cell in becoming one of the many cell types in our body.  University of Toronto scientist, Dr. William Stanford and his team describe their research in the journal Cell Stem Cell.

Stem Cell Prediction: This is a neat study.  Researchers generated an algorithm to predict the future of a stem cell – whether it divides and self-renew as stem cells or produce alternate cell types.  They recorded video of retinal progenitor cells under the microscope to ‘observe’ the cell’s characteristic dynamic behaviour and movements just prior to dividing.  This information was computed to generate a predictive algorithm that was tested to be (amazingly!) 99% accurate in identifying cells that will self-renew as stem cells and 87% correct in predicting a differentiation cell fate.  This may lead to new tools to help scientists isolate pure populations of stem cells for their future studies.  Dr. Michel Cayouette’s group at the Institut de Recherches Cliniques de Montréal presents their work in this week’s edition of Nature Methods.

Genomics of Flesh-eating Disease: The genomic sequences of Streptococcus bacterial strains from past epidemics in Ontario were determined in a study involving Canadian and US researchers.  They identified and compared single nucleotide polymorphisms (SNPs) between the strains and found that they were different by an average of only 49 SNPs.  Each strain, however, also contained unique sequences that could be used for tracking purposes in future outbreaks.  Some genes were highly variable, which is information that they can use to try to understand the bacterial virulence factors at play in gaining an advantage over the infected person.  These comparative pathogenomic studies are invaluable for microbial epidemiology research and for shedding light on new potential targets for antibiotic drugs.  Drs. Donald Low and Allison McGeer at Mount Sinai Hospital participated in the research that is reported in this week’s edition of the Proceedings of The National Academy of Sciences.

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.

Friday Science Review: December 11, 2009

WOW!  A busy week in the bioscience world…

Pull Down Your ‘SOCS’ and Grow Some Nerves: A long standing question is how to get mature neurons, which stop growing at around the age of two, to start growing again after sustaining nerve damage.  The answer may lie in a protein called SOCS3 (suppressor of cytokine signaling 3).  SOCS3 controls neuronal growth in adults but when it is absent (in a knockout mouse model), axons can regenerate after nerve injury.  This process may be enhanced by supplying a cocktail of neurotrophic growth factors that the researchers also identified in their study.  This is a very important discovery that will push regenerative medicine to new therapeutic strategies.  Dr. Patrice Smith started the research as a postdoctoral fellow at Harvard University and now runs her own lab at Carleton University.  The study is published in the latest edition of Neuron.  There is also an inspirational story about Dr. Smith in the Globe and Mail.

Protecting your Brain after a Stroke: Following a stroke, neurons are at risk of permanent damage caused by overactivation of NMDARs (N-methyl-D-aspartate glutamate receptors).  A key molecular step leading to this excitotoxic neuronal death was discovered in this recent study.  The trauma causes degradation of Insig-1 (insulin-induced gene-1), which triggers the activation of the transcription factor SREBP-1 (sterol regulatory element binding protein-1).  However, when they blocked the activation of SREBP-1 they were successful in reducing the neuronal damage.  This is a promising target for generating therapeutic drugs aimed at minimizing the detrimental effects of strokes and brain trauma.  The research team was guided by Dr. Yu Tian Wang at the University of British Columbia and the study is reported in the latest Nature Medicine.

Breakthrough in Children’s Brain Cancer Research: A rare pediatric brain tumour called Central Nervous System-Primitive Neuroectodermal Tumours (CNS-PNET) offers a very poor prognosis for young patients.  In this gene expression study, a cluster of microRNAs called C19MC was found to be amplified in the diseased tissue in about 25% of the patients. This cluster acts as an oncogene that enhances cell growth and affects differentiation of neural stem cells.   The new discovery will advance opportunities to study this rare pediatric cancer and possibly use C19MC as a diagnostic marker and/or therapeutic target.  The international study was led by Dr. Annie Huang at SickKids Hospital and is reported in the current issue of Cancer Cell.

Genomics Study on Pathogenic Factors: In a large scale study of bacterial genomes, it was proven broadly across microbial species that many of the bacterial virulence factors are contained within genomic islands or clusters of genes.  The virulence factors are proteins that have more “offensive” functions such as toxins that help the bacteria invade the host.  Another significant outcome of this research is the discovery of potentially new pathogen-associated genes that are present pre-dominantly in pathogenic bacteria but less frequently in the non-pathogenic bacteria.  These factors require a closer look as they may represent novel targets for anti-microbial drug development, a critical area of research to combat the increasing prevalence of drug resistant bacteria.   Dr. Fiona Brinkman’s team at Simon Fraser University conducted the research and is detailed in PLoS One.

Dabigatran vs. Warfarin (round 2): Following up on a study that I mentioned here earlier this year, new research further supports the use of Dabigatran over Warfarin.  Patients with a common clotting disorder called venous thromboembolism (VTE) can benefit from Dabigatran as an equally effective and safe blood thinning treatment but without the complications associated with using Warfarin, which requires frequent visits to the clinic for blood monitoring and dosage adjustments.  The study was conducted by Dr. Sam Schulman at McMaster University and appears in this week’s The New England Journal of Medicine.

Research on Congenital Myopathy in Mice:  University of Toronto scientists have generated a mouse model to study a specific type of skeletal muscle disorder.  The mice express a mutant form of the RyR1 protein (type 1 ryanodine receptor/Ca2+ release channel), which causes a severe form of central core disease (CCD). Symptoms in mice that mimic the human condition include progressive congenital myopathy, respiratory stress, skeletal muscle weakness and impaired mobility.  Their study offers insight and future potential to unravel the mechanism behind the disorder.  Dr. David MacLennan’s research is published in The Proceedings of the National Academy of Sciences.

Here is a list of many more important research reports this week from across the country:

Cofactor-activated phosphorylation is required for inhibition of cortical neuron differentiation by Groucho/TLE1. (Dr. Stefano Stifani, McGill University)

Dlx5 Is a cell autonomous regulator of chondrocyte hypertrophy in mice and functionally substitutes for Dlx6 during endochondral ossification. (Dr. Andrew Bendall, University of Guelph)

Pluripotent transcription factors possess distinct roles in normal versus transformed human stem cells. (Dr. Mickie Bhatia, McMaster University)

Nfil3/E4bp4 is required for the development and maturation of NK cells in vivo. (Dr. Tak Mak, The Campbell Family Institute for Breast Cancer Research and University of Toronto).

A novel enediynyl peptide inhibitor of furin that blocks processing of proPDGF-A, B and proVEGF-C. (Dr. Amik Basak, University of Ottawa)

The specificity of the FOXL2 c.402C>G Somatic mutation: a survey of solid tumors. (Dr. David Huntsman, University of British Columbia)

Nuclear function of Smad7 promotes myogenesis. (Dr. John McDermott, York University)

Asf1-like structure of the conserved Yaf9 YEATS domain and role in H2A.Z deposition and acetylation. (Dr. Michael Kobor, University of British Columbia)

Friday Science Review: November 27, 2009

Two quick reviews on studies addressing Alzheimer’s and lung damage therapy…

An ‘- omics’ Study of Lipids in Alzheimer’s Disease: Clues to the underlying molecular mechanisms of amyloid plaque proteins causing Alzheimer’s disease were revealed using a lipidomic method (think broad ‘-omics’ type profiling of lipids).  In diseased tissue, accumulation of certain isoforms or types of lipids is associated with hyperphosphorylation of the tau protein, which destabilizes neuronal cells and leads to neuronal cell death.  The researchers also demonstrated that pharmacological modulation of lipid metabolism has positive effects in protecting the integrity of the neurons and may be a strategy to prevent further decline in patients suffering from the disease.  Dr. Steffany Bennett and her research team at the University of Ottawa published the study in the Proceedings of the National Academy of Sciences.

Stem Cell Therapy for Lung Damage:  Premature newborns often suffer lung damage that leads to chronic lung disease.  However, new research using mesenchymal stem cells injected into the lungs shows promise in stimulating lung repair.  The study by Dr. Bernard Thébaud and his team at the University of Alberta in Edmonton used newborn rats as the subjects to test their hypothesis.  What is surprising is that it does not appear that the stem cells establish themselves in place of the damaged cells.  Instead, they act protectively to allow the lung to repair themselves and this may involve the release of factors from the stem cells to stimulate the regeneration process.  This strategy holds a lot of promise and hopefully the same is true in humans.  The study is a first on stem cell therapy in newborn lungs and is reported in the American Journal of Respiratory and Critical Care Medicine.

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Friday Science Review: October 30, 2009

Regenerative medicine and Cross-border awards…

Gene Therapy Saves Donor Lungs: A technique using gene therapy on donor lungs before transplantation may be used to repair and save damaged lungs, making them potentially suitable for transplantation into patients.  The procedure involves first preserving the lungs at normal body temperature in a protective chamber called the Toronto XVIVO Lung Perfusion System, which continuously pumps a solution of oxygen, proteins and nutrients.  Next, adenovirus gene therapy is used to introduce the IL-10 cytokine gene into the lungs.  IL-10 helps to decrease inflammation, which would lead to improved health and function of the donor lungs and better outcome for the patient.

Dr. Shaf Keshavjee, the project leader at the McEwen Centre for Regenerative Medicine, describes the rationale:

“It’s as if gene therapy turbocharges each individual cell to manufacture many more proteins in its own IL-10 factory.”

“This protein down-regulates or decreases the inflammatory potential of cells injured before and during the transplant process. It also has the capacity to turn down the recipient’s immune system which rejects the transplanted organ.”

The research study is reported in this week’s issue of Science, Translational Medicine.

A Platform to Test Cardiac Cell Therapy:  A model system for evaluating stem cell transplant in cardiac cell therapy to repair damaged heart tissue is described in this study by Drs. Peter Zandstra and Milica Radisic’s team at the University of Toronto.  Using their engineered heart tissue (EHT) as the analytical platform, they applied stem-cell derived cardiac cells and measured molecular and electrophysiological parameters of the EHT.  The system was verified as a predictive strategy to interrogate different cell transplantation conditions for the capacity to survive and functionally integrate into heart tissue.  This tool should help researchers accelerate development of cardiac cell therapy strategies and it can also provide mechanistic insight into the challenges of a successful transplant.  On a personalized medicine theme, an advantage of the system is that the EHTs are customizable and can be derived from individuals for patient specific testing prior to the actual treatment.  The study appears in this week’s edition of the Proceedings of the National Academy of Sciences.

“Cross-border” Cancer Stem Cell Therapy Award: The Collaborative Partnership Program between the California Institute for Regenerative Medicine (CIRM) and the Cancer Stem Cell Consortium (CSCC) in Canada have awarded two internationally recognized Canadian researchers with support to lead their respective cancer stem cell based therapy projects.

One project will develop agents to directly target leukemic stem cells that are resistant to current therapies.  This will be co-led by Dr. John Dick, Princess Margaret Hospital and Dr. Dennis Carson, University of California San Diego.

The other project will develop small molecules targeting cancer-initiating cells within solid tumor cancers and will be co-led by Dr. Tak Mak, Princess Margaret Hospital and Dr. Dennis Slamon, University of California, Los Angeles.

The awards offer each project up to $40 million (USD) over four years, with funding for the Canadian investigators contributed by Genome Canada and Canadian Institutes of Health Research through the CSCC and funding for the Californian investigators contributed by CIRM.

Congratulations to Drs. John Dick and Tak Mak!

Top 10The Scientist magazine ranked Dalhousie University in Halifax and the University of Toronto in the top 10 best places to work in academia outside of the U.S. Based on a web survey of scientists regarding job satisfaction, pay, research resources and relationships with their peers and management, Dalhousie ranked 5th and U of T came in at 10th place.  It is very nice to see Canadian institutions and our great research environment recognized by peers around the world.

Bailout Update: New UK Life Sciences Blueprint Aims to Promote Innovation

world_map_2002The UK has a new Life Sciences Blueprint that sets as a goal the creation of an internationally-recognized life sciences cluster.  Here’s the press release and here’s the full report (pdf). 

Innovation Pass and Changes at NICE:

The Blueprint kicks off an “Innovation Pass” program under which certain novel medicines (criteria TBD) will be available for a 3-year period without the otherwise mandatory predicate of review by the National Institute for Health and Clinical Excellence (NICE).  A further report is due from Sir Ian Kennedy next week (July 22) that aims “to identify the aspects of value and innovation which NICE should take into account in its work.”  If innovation stimulus is considered a part of the comparative effectiveness analysis, who knows how widely the door may open even after the Innovation Pass. 

Between these changes and the recent report on genomic medicine from the House of Lords Science and Technology Committee, which recommends that the purview of NICE be extended to “include a programme for evaluating the validity, utility and cost-benefits of all new genomic tests for common diseases, including pharmacogenetic tests,” big changes may be heading NICE’s way.

Also notable:

  • The Government will invest £150 million alongside private sector investment, with the aim of leveraging enough private investment to build a £1bn, 10-year Venture Capital Fund.  This is Lord Drayson’s idea that we held up at the time as a model for technology-agnostic lobbying;
  • Along with a variety of educational initiatives and programs, the Society of Biology will begin to accredit undergraduate bioscience degrees to help ensure that graduates leave with the core skills and competencies required by employers;
  • A reassessment of the UK’s various R&D tax incentive programs (A little tax joke for you there as a prize for making it this far down the post.);
  • An £18 million program for regenerative medicine R&D; and of course
  • A marketing initiative to make sure everyone knows all the great stuff they’re doing.

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