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News Article | February 21, 2017

HOUSTON, Feb. 21, 2017 (GLOBE NEWSWIRE) -- Bio-Path Holdings, Inc., (NASDAQ:BPTH), a biotechnology company leveraging its proprietary DNAbilize™ liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer drugs, today announced the appointment of D. Craig Hooper, Ph.D., to its Scientific Advisory Board (SAB). “It is with great pleasure we welcome Dr. Hooper to our SAB. His extensive experience in the neuroimmunology field will be extremely valuable to Bio-Path as we seek to advance our liposomal RNAi antisense platform to deliver a safe and systemic brain cancer immunotherapy,” said Peter Nielsen, President and Chief Executive Officer of Bio-Path. “Bio-Path is developing a truly innovative platform that has the potential to transform antisense drug delivery,” commented Dr. Hooper. “I’m honored to join Bio-Path’s SAB and look forward to working with my esteemed colleagues to help advance DNAbilize™ and offer meaningful new immunotherapy treatments to patients.” D. Craig Hooper, Ph.D., is a Professor of Cancer Biology and Neurological Surgery at Thomas Jefferson University. Dr. Hooper has published over 140 papers in peer-reviewed journals and serves on the editorial boards of the Journal of Immunology Research, Scientific Reports and the Journal of Immunology. In 2016 he was inducted into the National Academy of Inventors (NAI). Dr. Hooper received his Ph.D. in Immunology and B.Sc. in Physiology from McGill University. He completed his post-doctoral research fellowship at the University of Bristol. Bio-Path is a biotechnology company focused on developing therapeutic products utilizing DNAbilize™, its proprietary liposomal delivery and antisense technology, to systemically distribute nucleic acid drugs throughout the human body with a simple intravenous transfusion. Bio-Path’s lead product candidate, prexigebersen (BP1001, liposomal Grb2 antisense), is in a Phase II study for blood cancers and in preclinical studies for solid tumors. Bio-Path’s second drug candidate, also a liposomal antisense drug, is ready for the clinic where it will be evaluated in lymphoma and solid tumors. For more information, please visit the Company's website at

News Article | November 18, 2016

WASHINGTON, DC - A Children's National Health System research team has uncovered a novel process by which the gene APOL1 contributes to renal disease, according to a paper published November 18 in the Journal of the American Society of Nephrology. Mutated versions of the APOL1 gene render people of African descent at heightened risk of developing chronic kidney disease. Employing powerful genetic approaches, Children's National researchers were able to mimic APOL1 renal cell pathology in the fruit fly Drosophila melanogaster. This opens the door to pinpointing other proteins that interact with APOL1, a vital first step toward identifying medicines to treat renal diseases that currently have no drug therapy. "This is one of the hottest research topics in the kidney field. We are the first group to generate this result in fruit flies," says Zhe Han, PhD, a senior Drosophila specialist and associate professor in the Center for Cancer & Immunology Research at Children's. Han, senior author of the paper, will present the study results this week during Kidney Week 2016, the American Society of Nephrology's annual gathering in Chicago that is expected to draw more than 13,000 kidney professionals from around the world. The advantages of Drosophila for biomedical research include its rapid generation time and an unparalleled wealth of sophisticated genetic tools to probe deeply into fundamental biological processes underlying human diseases. People of African descent frequently inherit a mutant version of the APOL1 gene that affords protection from African sleeping sickness, but is associated with a 17- to 30-fold greater chance of developing certain types of kidney disease. That risk is even higher for individuals infected with the human immunodeficiency virus (HIV). Drosophila renal cells, called nephrocytes, accurately mimic pathological features of human kidney cells during APOL1-associated renal disease. "Nephrocytes share striking structural and functional similarities with mammalian podocytes and renal proximal tubule cells, and therefore provide us a simple model system for kidney diseases," says Han, who has studied the fruit fly for 20 years and established the fly nephrocyte as a glomerular kidney disease model in 2013 with two research papers in the Journal of the American Society of Nephrology. In this most recent study, Han's team cloned a mutated APOL1 gene from podocyte cells cultured from a patient with HIV-associated nephropathy. They created transgenic flies making human APOL1 in nephrocytes and observed that initially the transgene caused increased cellular functional activity. As flies aged, however, APOL1 led to reduced cellular function, increased cell size, abnormal vesicle acidification, and accelerated cell death. "The main functions of nephrocytes are to filter proteins and remove toxins from the fly's blood, to reabsorb protein components, and to sequester harmful toxins. It was surprising to see that these cells first became more active and temporarily functioned at higher levels," says Han. "The cells got bigger and stronger but, ultimately, could not sustain that enhancement. After swelling to almost twice their normal size, the cells died. Hypertrophy is the way that the human heart responds to stress overload. We think kidney cells may use the same coping mechanism." The Children's research team is a multidisciplinary group with members from the Center for Cancer & Immunology Research, the Center for Genetic Medicine Research, and the Division of Nephrology.The team also characterized fly phenotypes associated with APOL1 expression that will facilitate the design and execution of powerful Drosophila genetic screening approaches to identify proteins that interact with APOL1 and contribute to disease mechanisms. Such proteins represent potential therapeutic targets. Currently, transplantation is the only option for patients with kidney disease linked to APOL1. "This is only the beginning," Han says. "Now, we have an ideal pre-clinical model. We plan to start testing off-the-shelf therapeutic compounds, for example different kinase inhibitors, to determine whether they block any of the steps leading to renal cell disease."

News Article | February 22, 2017

Two drugs used to treat asthma and allergies may offer a way to prevent a form of pneumonia that can kill up to 40 percent of people who contract it, researchers at the University of Virginia School of Medicine have found. Influenza pneumonia results when a flu infection spreads to alveolar air sacs deep within the lungs. Normally, a flu infection does not progress that far into the lower respiratory tract, but when it does, the results can be deadly. "If infection is severe enough, and the immune response is potent enough, you get injury to these cells and are no longer able to get sufficient oxygen exchange," explained UVA researcher Thomas J. Braciale, MD, PhD. "As a result of the infection of the cells, you can develop lethal pneumonia and die." But early administration of the two asthma drugs, Accolate and Singulair, could prevent the infection of the alveolar cells deep in the lower respiratory tract, Braciale's research suggests. "The excitement of this is the possibility of someone coming to see the physician with influenza that looks a little more severe than usual and treating them with the drugs Singulair or Accolate and preventing them from getting severe pneumonia," he said. "The fatality rate from influenza pneumonia can be pretty high, even with all modern techniques to support these patients. Up to 40 percent. So it's a very serious problem when it occurs." Unlike bacterial pneumonia, influenza pneumonia is caused by a virus. That makes it very difficult to treat - and makes the possibility of prevention all the more tantalizing. "When we look at pandemic strains of influenza that have high mortality rates, one of the best adaptations of those pandemic viruses is their ability to infect these alveolar epithelial cells," explained researcher Amber Cardani, PhD. "It's one of the hallmarks for certain strains that cause the lethality in these pandemics." Once influenza spreads deep into the lungs, the body's own immune response can prove harmful, resulting in severe damage to the alveolar air sacs. "It's an important observation the field is coming to," Cardani said. "We really need to limit the infection of these lower respiratory airways." The researchers determined that the alveolar epithelial cells are typically protected from influenza infection by immune cells called alveolar macrophages. In some instances, however, the flu virus can prevent the macrophages from carrying out their protective function, allowing the epithelial cells to become vulnerable to infection. "It's not as though they lack alveolar macrophages, it's just that their alveolar macrophages don't work right when they get exposed to the flu," Braciale said. "And those are the types of patients, who potentially would eventually go to the intensive care unit, that we think could be treated early in infection with Accolate or Singulair to prevent infection of these epithelial cells and prevent lethal infection." For their next steps, the researchers are consulting with colleagues to determine if patients being treated with Accolate and Singulair are less likely to develop influenza pneumonia during flu outbreaks. "This was a totally unexpected observation," Braciale said. "When I told multiple colleagues who are infectious disease or pulmonary physicians, they were absolutely flabbergasted." The findings have been published by the scientific journal PLOS Pathogens. It was written by Cardani, Adam Boulton, Taeg S. Kim and Braciale. Braciale and Cardani are both part of UVA's Department of Microbiology, Immunology and Cancer Biology and UVA's Beirne B. Carter Center for Immunology Research. Braciale's primary appointment is with the Department of Pathology. The work was supported by the National Institutes of Health, grant R01AI015608-35, and the NIH's National Institute of General Medical Sciences, grants T32 GM007055 and T32 GM007055.

DRI Utilizes Funding to Launch Lindsey Inserra-Hughes Immune Tolerance Seminar Series to Advance Immunology Research for Type 1 Diabetes

News Article | February 10, 2017

Specific genetic errors that trigger congenital heart disease (CHD) in humans can be reproduced reliably in Drosophila melanogaster - the common fruit fly - an initial step toward personalized therapies for patients in the future. "Studying CHD in fruit flies provides a fast and simple first step in understanding the roles that individual genes play in disease progression," says Zhe Han, Ph.D., a principal investigator and associate professor in the Center for Cancer & Immunology Research at Children's National Health System and senior author of the paper published Jan. 20, 2017 in eLife. "Our research team is the first to describe a high-throughput in vivo validation system to screen candidate disease genes identified from patients. This approach has the potential to facilitate development of precision medicine approaches for CHD and other diseases associated with genetic factors," Han says. Some 134 genes have been implicated in causing CHD, a birth defect that affects 8 in 1,000 newborns, according to the National Institutes of Health. The research team led by Han used high-throughput techniques to alter the activity of dozens of genes in flies' hearts simultaneously in order to validate genes that cause heart disease. "Our team was able to characterize the effect of these specific genetic alterations on heart development, structure and activity," Han adds. "The development of the human heart is a complicated process in which a number of different cell types need to mature and differentiate to create all of the structures in this essential organ. The precise timing of those cellular activities is critical to normal heart development, with disruptions in the structure of proteins called histones linked to later heart problems.". Of 134 genes studied by the research team, 70 caused heart defects in fruit flies, and several of the altered genes are involved in modifying the structure of histones. Quantitative analyses of multiple cardiac phenotypes demonstrated essential structural, functional and developmental roles for these genes, including a subgroup encoding histone H3K4 modifying proteins. The scientists then corroborated their work by reliably reproducing in flies the effect of specific genetic errors identified in humans with CHD. "This may allow researchers to replicate individual cases of CHD, study them closely in the laboratory and fashion treatments personalized to that patient specifically," he adds. "Precise gene-editing techniques could be used to tailor-make flies that express a patient's specific genetic mutation. Treating CHD at the level of DNA offers the potential of interrupting the current cycle of passing along genetic mutations to each successive generation."

PubMed | Medicinal Chemistry, Immunology Research, Translational science Pathology and Translational science Genetics & Genomics
Type: Journal Article | Journal: Immunology | Year: 2016

Retinoic acid receptor-related orphan nuclear receptor (ROR) orchestrates a pro-inflammatory gene expression programme in multiple lymphocyte lineages including T helper type 17 (Th17) cells, T cells, innate lymphoid cells and lymphoid tissue inducer cells. There is compelling evidence that ROR-expressing cells are relevant targets for therapeutic intervention in the treatment of autoimmune and inflammatory diseases. Unlike Th17 cells, where ROR expression is induced under specific pro-inflammatory conditions, T cells and other innate-like immune cells express ROR in the steady state. Small molecule mediated disruption of ROR function in cells with pre-existing ROR transcriptional complexes represents a significant and challenging pharmacological hurdle. We present data demonstrating that a novel, selective and potent small molecule ROR inhibitor can block the ROR-dependent gene expression programme in both Th17 cells and ROR-expressing T cells as well as a disease-relevant subset of human ROR-expressing memory T cells. Importantly, systemic administration of this inhibitor in vivo limits pathology in an innate lymphocyte-driven mouse model of psoriasis.

Hacha J.,University of Liège | Tomlinson K.,Immunology Research | Maertens L.,University of Liège | Paulissen G.,University of Liège | And 6 more authors.
American Journal of Respiratory Cell and Molecular Biology | Year: 2012

IL-13 is a prototypic T helper type 2 cytokine and a central mediator of the complex cascade of events leading to asthmatic phenotype. Indeed, IL-13 plays key roles in IgE synthesis, bronchial hyperresponsiveness, mucus hypersecretion, subepithelial fibrosis, and eosinophil infiltration. We assessed the potential efficacy of inhaled anti-IL-13 monoclonal antibody Fab' fragment on allergen-induced airway inflammation, hyperresponsiveness, and remodeling in an experimental model of allergic asthma. Anti-IL-13 Fab' was administered to mice as a liquid aerosol generated by inExpose inhalation system in a tower allowing a nose-only exposure. BALB/c mice were treated by PBS, anti-IL-13 Fab', or A33 Fab' fragment and subjected to ovalbumin exposure for 1 and 5 weeks (short-term and long-term protocols). Our data demonstrate a significant antiasthma effect after nebulization of anti-IL-13 Fab' in a model of asthma driven by allergen exposure as compared with saline and nonimmune Fab fragments. In short- and long-term protocols, administration of the anti-IL-13 Fab' by inhalation significantly decreased bronchial responsiveness to methacholine, bronchoalveolar lavage fluid eosinophilia, inflammatory cell infiltration in lung tissue, and many features of airway remodeling. Levels of proinflammatory mediators and matrix metalloprotease were significantly lower in lung parenchyma of mice treated with anti-IL-13 Fab'. These data demonstrate that an inhaled anti-IL-13 Fab' significantly reduces airway inflammation, hyperresponsiveness, and remodeling. Specific neutralization of IL-13 in the lungs using an inhaled anti-IL-13 Fab' could represent a novel and effective therapy for the treatment of asthma. Copyright © 2012 by the American Thoracic Society.

Sivakumar P.,Immunology Research | Ntolios P.,University College London | Jenkins G.,University of Nottingham | Laurent G.,University College London
Current Opinion in Pulmonary Medicine | Year: 2012

PURPOSE OF REVIEW: This review describes the challenges created by the existence of multiple molecular pathways leading to fibrosis and proposes that attention be focused on targeting the fibroblasts and myofibroblasts which themselves produce multiple cytokines and growth factors as well as the extracellular matrix, which is the hallmark of fibrotic lung disease. RECENT FINDINGS: The last 20 years have seen remarkable progress in our understanding of the molecular pathogenesis of pulmonary fibrosis leading to multiple programmes in drug discovery, and there are currently 15 actively recruiting trials registered on Unfortunately, at this time only one new drug, pirfenidone, has progressed to approval for use in patients. Part of the frustration is that drugs that are effective in targeting inflammatory pathways have been ineffective in lung fibrosis. This may result from the inability to treat patients early in the disease process but it is also likely that pathways independent of inflammation can drive fibrosis. SUMMARY: We further propose that this approach should inhibit fibrosis independent of cell type or the signalling cascade that is activating these cells. We are hopeful that the next 20 years will see many more therapeutic options for patients suffering with fibrotic lung disease. Copyright © 2012 Lippincott Williams & Wilkins.

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