Syndicate content

Archive - Jan 2018


January 7th

Gene Therapy Restores Normal Blood Glucose Levels in Mice with Type 1 Diabetes

Type 1 diabetes is a chronic disease in which the immune system attacks and destroys insulin-producing beta cells in the pancreas, resulting in high blood levels of glucose. A study published in the January 4, 2018 of Cell Stem Cell demonstrates that a gene therapy approach can lead to the long-term survival of functional beta cells, as well as normal blood glucose levels for an extended period of time in mice with diabetes. The researchers used an adeno-associated viral (AAV) vector to deliver to the mouse pancreas two proteins, Pdx1 and MafA, which reprogrammed plentiful alpha cells into functional, insulin-producing beta cells. The article is titled "Endogenous Reprogramming of Alpha Cells into Beta Cells, Induced by Viral Gene Therapy, Reverses Autoimmune Diabetes." "This study is essentially the first description of a clinically translatable, simple single intervention in autoimmune diabetes that leads to normal blood sugars, and importantly with no immunosuppression," says senior study author George Gittes, MD, of the University of Pittsburgh School of Medicine. "A clinical trial in both type 1 and type 2 diabetics in the immediate foreseeable future is quite realistic, given the impressive nature of the reversal of the diabetes, along with the feasibility in patients to do AAV gene therapy." Approximately 9% of the world's adult population has diabetes, which can cause serious health problems such as heart disease, nerve damage, eye problems, and kidney disease. One fundamental goal of diabetes treatment is to preserve and restore functional beta cells, thereby replenishing levels of a hormone called insulin, which moves blood glucose into cells to fuel their energy needs.

January 5th

IV-Delivered Healing Exosomes Derived from Mesenchymal Stem Cells Specifically Target Healing M2-Type Macrophages in a Rat Model Spinal Cord Injury

Scientists at the Yale University School of Medicine have shown that, in a rat model of spinal cord injury (SCI), intravenously delivered exosomes from bone-marrow-derived mesenchymal stem cells (MSCs) rapidly associate specifically with M2-type healing macrophages at the site of the SCI, but not in the uninjured spinal cord. The researchers believe that their findings support the idea that such extracellular vesicles, released by MSCs, may mediate at least some of the therapeutic healing effects of IV MSC administration. The new work follows on a 2015 study (in Experimental Neurology), by members of the Yale group, that showed that IV infusion of bone marrow-derived MSCs improved functional and anatomical recovery after contusive SCI in the non-immunosuppressed rat, although the MSCs themselves were not detected at the spinal cord injury (SCI) site ( The new work was published on January 2, 2018 in PLOS ONE. The open-access article is titled “Intravenously Delivered Mesenchymal Stem Cell-Derived Exosomes Target M2-Type Macrophages in the Injured Spinal Cord.” The authors also reported, in their new study, that the MSC exosomes were also detected in the spleen, which was notably reduced in weight in the rats with SCI. The researchers noted that further work is need to needed to determine whether IV exosomes fully replicate the therapeutic actions of MSCs on SCI recovery, as well as to elucidate the possible role of the spleen in SCI recovery. The authors of this work are Karen L. Lankford, Edgar J. Arroyo, Katarzyna Nazimek, Krysztof Bryniarski, Philip W. Askenase, and Jeffrey D. Kocsis, all affiliated with the Yale University School of Medicine.

Cicada Symbiotic Complexes of Bacteria Are Different from Any Known Organism

University of Montana (UM) researchers have made a discovery at the cellular level to help understand the basic processes of all life on our planet - this time within the unusual bacteria that has lived inside cicada insects since dinosaurs roamed Earth. During the past 70 million years, the bacteria underwent extreme adaptations to live within the insects' bodies, losing between an estimated 95 to 97 percent of their genes and resulting in some of the smallest genomes known to any organisms. In the process, they lost the ability to live anywhere outside of cicadas. "Cicada symbiotic complexes are very different from any other known organism," said Matt Campbell, a UM graduate student who studies cicadas in UM Biology Associate Professor John McCutcheon's lab, based in the Division of Biological Sciences. Many insects live in very close associations with symbiotic bacteria. These bacterial symbioses are critically important for insects that consume only one type of food that is missing some essential nutrients. Examples include blood-feeding lice, as well as insects that feed on plant sap - aphids, leafhoppers, and cicadas. The UM research has shown that cicadas' symbiotic bacteria produce amino acids and vitamins that their insect hosts require to grow and reproduce. During three field seasons studying a South American cicada, UM postdoctoral researcher Dr. Piotr Lukasik found that many of the species' single symbiotic bacterium evolved into complexes of several different types of bacterium in the same cicada. "Through that process, individual bacteria have lost many genes and now depend on each other because every type contains unique, essential genes," Dr. Lukasik said.

Treeshrews Defy Evolutionary Rules

A new study has exposed the common treeshrew, a small and skittish mammal that inhabits the tropical forests of Southeast Asia, as an ecogeographical rule breaker. According to the study, published online on January 4, 2017 in Ecology and Evolution, Tupaia glis, the common treeshrew, defies two widely tested rules that describe patterns of geographical variation within species: the “island rule” and “Bergmann's rule.” The open-access article is titled “Rule Reversal: Ecogeographical Patterns of Body Size Variation in the Common Treeshrew (Mammalia, Scandentia).” The island rule predicts that populations of small mammals evolve larger body size on islands than on the mainland, whereas island-bound large mammals evolve smaller body size than their mainland counterparts. Bergmann's rule holds that populations of a species in colder climates, generally located at higher latitudes, have larger body sizes than populations in warmer climates, which are usually at lower latitudes. In order to determine treeshrew body size from populations on the Malay Peninsula and 13 offshore islands, the researchers measured 260 specimens collected over the past 122 years and housed in 6 natural history museums in Europe and North America. The researchers tested multiple variables, analyzing how island size, distance from the mainland, maximum sea depth between the mainland and the islands, and latitude relate to body size in the treeshrew populations. They found that the island rule and Bergmann's rule, which are rarely tested together, do not apply to common treeshrews. The study revealed no size difference between mainland and island populations. It also revealed that treeshrews invert Bergmann's rule: individuals from lower latitudes tended to be larger than those located at higher latitudes.

Mismatch Repair Preferentially Targets Genes Rather Than Non-Genic Regions in Arabidopsis

Researchers at the University of Oxford have discovered that a cellular mechanism preferentially protects plant genes from the damaging effects of mutation. Whilst DNA sequence mutation is the fundamental fuel of species evolution, mutations in genes are often harmful. As a form of defense, organisms have evolved repair mechanisms to correct the DNA sequence following mutation. One of these mechanisms, is termed DNA mismatch repair (MMR). It corrects mutations that arise during the replication of the genome during cell division. A new study, published in the January 2018 issue of Genome Research, has shown for the first time that MMR is targeted to particular regions of the genome, and preferentially repairs genes. The article is titled “DNA Mismatch Repair Preferentially Protects Genes from Mutation.” The research was carried out in the Department of Plant Sciences, together with colleagues from Zhejiang University (China) and Lahore University of Management Studies (Pakistan). Led by Oxford's Professor Nicholas Harberd, the team looked at 9,000 mutations accumulated in five generations of an MMR-deficient strain of the model plant species Arabidopsis thaliana, and compared them with mutations arising in an MMR-proficient strain. The study has important implications for human health, and is particularly useful for understanding the changes that occur in cells during the development of the tumors that underlie cancers. MMR-deficiency predisposes cells to become tumorous, presumably because MMR-deficient cells lack the gene protection that reduces the risk of mutation in the genes that normally suppress tumor formation. The team has no plans to expand on these implications, but would welcome interest from anyone keen to follow up the study from a medical science perspective.

January 4th

Combination of Oncolytic Virus and Checkpoint Inhibitor Shows Treatment Effectiveness in Mouse Models of Triple-Negative Breast Cancer

The Alliance for Cancer Gene Therapy (ACGT), a non-profit based in Stamford, Connecticut, dedicated to funding breakthrough cancer gene therapy treatments, has had its funding pay off with a promising study on breast cancer coming out of The Ottawa Hospital and the University of Ottawa in Ottawa, Canada. The study suggests that a combination of two immunotherapies -- oncolytic viruses and checkpoint inhibitors -- could be much more successful than traditional treatments in fighting breast cancer and possibly other cancers. The study, which used mouse models, was published in the January 3, 2018 issue of Science Translational Medicine and was conducted by ACGT grantee, Dr. John Bell, and his research lab, in conjunction with Dr. Marie-Claude Bourgeois-Daigneault, lead author of the study and postdoctoral fellow in Dr. Bell's research group. The article is titled “Neoadjuvant Oncolytic Virotherapy Before Surgery Sensitizes Triple-Negative Breast Cancer to Immune Checkpoint Therapy.” Cancer immunotherapy has proven to be a powerful tool in fighting cancer and has revolutionized treatment for cancers such as melanoma and leukemia. Unfortunately though, other forms of cancer, and especially solid tumor cancers, have remained resistant. ACGT has a track record of funding innovative, breakthrough cancer treatments and was one of the initial funders for laboratory research and clinical trials of immunotherapy in support of Dr. Carl June's work at the University of Pennsylvania, where Dr. June’s team has been successfully treating relapsed pediatric leukemia with gene therapy. ACGT started funding cancer cell and gene therapies in the early 2000's when it was still deemed “risky” science.

Adaptive Phage Therapeutics & Progress in Treating Deadly Multidrug-Resistant Bacterial Infections

On April 26, 2017, Adaptive Phage Therapeutics, Inc. (APT), a clinical-stage company founded to provide an effective therapeutic response to the global rise of multi-drug resistant (MDR) pathogenic bacteria, announced that a therapeutic approach leveraging bacteriophage (phage), as outlined in 2003 by NIH Emeritus Scientist, Carl R Merril, MD, (Merril, et al, Nature Reviews; Drug Discovery, 2003) had been used by the University of California-San Diego Medical Center to successfully rescue a terminally ill patient (Tom Patterson) infected with multidrug resistant Acinetobacter baumannii (MDRAB). A detailed story on the use of phage therapy to treat MDR pathogenic bacterial infections was published in the December 25, 2017 issue of Time Magazine ( Titled “Superbugs Are Nearly Impossible to Fight. This Last-Resort Medical Treatment Offers Hope” and authored by Alexandra Sifferlin, the Time story outlines the history of phage-based therapies, which actually dates back almost to the time phage were first discovered (just over 100 years ago). That history is fraught with controversy and mixed results, but great progress in molecular biology and, particularly, the very recent success in the treatment of Tom Patterson, have rekindled interest and hope in this approach to therapy to fight deadly MDR bacterial infections. The Time story also describes the very recent phage-based effort to save the life of 25-year-old Mallory Smith, a cystic fibrosis patient who was in critical condition with a drug-resistant Burkholderia cepacia infection. According to Time, after being notified of Mallory’s plight, APT identified a phage that might be able to kill the bacteria and shipped the virus to the University of Pittsburgh hospital where Mallory was being treated.

Differences in “Silent Code” of Nucleotides (Synonymous Codons), Not Amino Acids, Determine Functions of Actin Isoforms, According to Provocative New Study; Results May Point to Global Form of Functional Regulation

Humans possess six forms of the protein actin that perform essential functions in the body. Two in particular, β-actin and γ-actin, are nearly identical, differing only by four amino acids. Yet these near-twin proteins carry out distinct roles. A long-standing question for biologists has been, how is this possible? "It's a mystery that's been debated in the field for the past 40 years," said Anna Kashina (photo), PhD, a Professor of Biochemistry in the University of Pennsylvania School of Veterinary Medicine (Penn Vet). New findings by Dr. Kashina and colleagues have pointed to a surprising answer. The differing functions of these proteins are determined not by their amino acid sequences but by their genetic code. "We like to call it the 'silent code,'" Dr. Kashina said. "Our findings show that the parts of genes that we think of as being silent actually encode very key functional information." The researchers found that these "silent" differences in the nucleotide sequence seem to influence the density of ribosomes, the molecular machines that translate RNA into proteins. Such differences may enable each individual actin form to take on a different role in the cell. Dr. Kashina coauthored the work, published in the journal eLife, with Penn Vet's Pavan Vedula, Satoshi Kurosaka, Nicolae Adrian Leu, Junling Wang, Stephanie Sterling, and Dawei Dong and the National Institutes of Health's Yuri I. Wolf and Svetlana A. Shabalina. The article is titled “Diverse Functions of Homologous Actin Isoforms Are Defined by Their Nucleotide, Rather Than Their Amino Acid Sequence.” Actin is so ubiquitious and essential that it's known as a "housekeeping protein." It's the most abundant protein in most cells, and its different forms play roles during cell migration, muscle contraction, and development.

ArunA Biomedical Launches New Class of Exosome Biologics to Treat Central Nervous System and Neurodegenerative Disorders; Company Rapidly Moving Toward Clinical Development of Cell-Free Biologic Therapy, Plans to Initiate First-in-Human Studies in 2019

On January 3, 2018, ArunA Biomedical announced the official launch of a new class of cell-free exosome biologics to treat central nervous system and neurodegenerative disorders. With an initial focus on an exosome therapeutic for stroke, the company published, on January 3, 2018, results of a study in Translational Stroke Research that found that extracellular vesicles (EVs) derived from human neural stem cells improved tissue and functional recovery in murine thromboembolic stroke models. The open-access article is titled “Human Neural Stem Cell Extracellular Vesicles Improve Tissue and Functional Recovery in the Murine Thromboembolic Stroke Model.” The study was led by Dr. Steven Stice, a Georgia Research Alliance Eminent Scholar endowed chair, Professor and Director of the Regenerative Bioscience Center at The University of Georgia, and who serves as Co-Founder, Chief Executive, and Chief Scientific Officer for ArunA Biomedical. The study was conducted in collaboration with Dr. Nasrul Hoda at Augusta University in Augusta, Georgia. Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) were evaluated for changes in infarct volume as well as sensorimotor function. Results showed that the NSC EVs improved cellular, tissue, and functional outcomes in middle-aged rodents, whereas MSC EVs were less effective. Acute differences in lesion volume following NSC EV treatment were corroborated by MRI in aged rodents. NSC EVs mechanistically increased circulating regulatory T cell numbers, which are known to enhance remyelination in the injured brain. Specifically, neural stem cell EV treatment has a positive effect on motor function as indicated by beam walk, instances of foot faults, and strength evaluated by a hanging wire test.

January 3rd

Cancer Researchers Investigate How Cells Communicate Using Exosomes, with Special Focus on Increased Exosome Production by Glioblastoma Cells After Chemical Stimulation

by Zehui (Lesley) Li. (The following article was authored by Zehui (Lesley) Li (photo), a PhD student in the University of Toledo College of Medicine and Life Sciences Biomedical Science Program. Lesley is studying chemical messengers between cells and how they can potentially be used to treat cancer. Lesley is doing her research in the laboratory of William Maltese, PhD, in the Department of Cancer Biology. Lesley's article first appeared in Toledo’s "The Blade" newspaper on December 31, 2017, and is reprinted here with permission. Lesley’s article from The Blade follows here): Cells are the basic structural units that are used to build all of the organs in your body. A surface membrane surrounds each cell, just as your skin surrounds you. The cell membrane controls the entry and exit of different things, including food and specific molecules that can change the rate of cell growth and division. One way that the cell membrane can bring in other molecules is within small bubble-like structures that pinch off and move inside the cell. Such bubbles are called endosomes (inside cell). Once [formed] inside the cell, each endosome can make even smaller bubbles within it. These smaller bubbles are called intraluminal vesicles (ILVs). These ILVs are so small that they can only be seen using a very high-powered microscope. Scientists have now discovered that endosomes can return to the cell surface, where they fuse back with the cell membrane and release small ILV bubbles outside the cell. Once they leave the cell, the tiny bubbles are called exosomes (outside cell). These exosomes float in your body fluid and eventually attach to other cell membranes and enter the new cell. After they move in, molecules inside of the bubbles will be released into the new cell to affect cell growth and other cell activities.