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Once-a-Week Insulin Treatment Could Be Game-Changing for Patients with Diabetes

Treating people with Type 2 diabetes with a new once-a-week injectable insulin therapy proved to be safe and as effective as daily insulin injections, according to the results of two international clinical trials published online on April 19, 2021 in Diabetes Care. The studies suggest that the once-weekly treatment could provide a convenient alternative to the burden of daily insulin shots for diabetes patients.Starting and maintaining insulin treatment remain a challenge for millions of patients worldwide with Type 2 diabetes. Fear of injections and the inconvenience and burden of injectable therapy contribute to the barriers against insulin therapy initiation and adherence. The effectiveness and safety of ongoing insulin treatment are also highly dependent on other factors, such as the accuracy of dosages, timing, and glycemic targets. Health care providers believe that reducing the frequency of treatment administration with advances, such as the once-weekly insulin used in these phase 2 trials, may decrease the reluctance to initiate insulin therapy while improving long-term adherence, glucose control, and ultimately, patient well-being. “Insulin, which has been the foundation of diabetes treatment for 100 years, is an effective glucose-lowering agent and is safe when used at the correct dose,” says Ildiko Lingvay (photo), MD, MPH, a Professor of Internal Medicine and Population and Data Sciences at the University of Texas Southwestern (UTSW). “Insulin treatment is burdensome, requires frequent injections, and continues to carry a certain stigma. The development of an effective and safe insulin that can be administered once a week is a huge advance in the field.”

The Genome of a Certain Plankton (Dinoflagellate Symbiodinium microadriaticum) Looks Nothing Like That of Other Eukaryotic Genomes

The genome of certain single-celled plankton, known as dinoflagellates, is organized in an incredibly strange and unusual way, according to new research. The findings lay the groundwork for further investigation into these important marine organisms and dramatically expand our picture of what a eukaryotic genome can look like. Researchers from Saudia Arabia’s KAUST (King Abdullah University of Science and Technology), the U.S., and Germany have investigated the genomic organization of the coral-symbiont dinoflagellate Symbiodinium microadriaticum (image). The genome of S. microadriaticum genome had already been sequenced and assembled into segments known as scaffolds but lacked a chromosome-level assembly. The team used a technique known as Hi-C to detect interactions in the dinoflagellate’s chromatin, the combination of DNA and protein that makes up a chromosome. By analyzing these interactions, they could figure out how the scaffolds were connected together into chromosomes, giving them a view into the spatial and structural organization of the genome. A striking finding was that the genes in the genome tended to be organized in alternating unidirectional blocks. “That’s really, really different from what you see in other organisms,” says Octavio Salazar, a PhD student in Manuel Aranda's (PhD) group at KAUST and one of the lead authors of the study. The orientation of genes on a chromosome is usually random. In this case, however, genes were consistently oriented one way and then the other, with the boundaries between blocks showing up clearly in the chromatin interaction data. “Nature can work in a completely different way than we thought,” Salazar said.

Study Shows How Two Meningitis-Causing Bacteria May Sense Fever and Respond by Producing Protection Against Immune Attack; RNA Thermosensors (RNATs) Play Key Role

Researchers at Karolinska Institutet in Sweden have discovered a mechanism through which meningitis-causing bacteria can evade our immune system. In laboratory tests, they found that Streptococcus pneumoniae and Haemophilus influenzae (image) respond to increasing temperatures by producing safeguards that keep them from getting killed. This may prime their defenses against our immune system and increase their chances of survival, the researchers say. The findings were published online on April 29, 2021 in PLoS Pathogens. The open-access article is titled “RNA Thermosensors Facilitate Streptococcus pneumoniae and Haemophilus influenzae Immune Evasion” (https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat....). "This discovery helps to increase our understanding of the mechanisms these bacteria use to evade our normal immune defenses," says co-corresponding author Edmund Loh, PhD, researcher in the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet. "It could be an important piece of the puzzle in examining what turns these usually harmless bacteria into lethal killers." Meningitis is an inflammation of the membranes surrounding the brain and the spinal cord. It can be caused by viruses, bacteria, fungi, and parasites. Bacterial meningitis is one of the most severe types and a major cause of death and disability in children worldwide. Several kinds of bacteria can cause the infection, including the respiratory pathogens Streptococcus pneumoniae and Haemophilus influenzae, which are related to some 200,000 meningitis-caused deaths annually. These two bacteria often reside in the nose and throat of healthy people without making them ill. In some cases, they spread into the bloodstream and cause invasive diseases, but the reasons for this remain largely unknown.

Study Illuminates How COVID-19 May Gain Access to the Brain Via Interaction with Astrocytes; Both Astrocytes and Neurons Express ACE2 Receptor and Can Be Infected by SARS-CoV-2; But Astrocytes Less Susceptible to Infection Than Neurons

New research offers an up-close view of how SARS-CoV-2, the virus that causes COVID-19, can spread to the brain. The study helps explain the alarming array of neurological symptoms reported in some patients with COVID-19, as well as why some patients suffer severe neurological effects while others experience none at all. The researchers report evidence that SARS-CoV-2 can infect both the nerve cells that power our brains (neurons), and the cells in the brain and spinal cord that support and protect neurons (astrocytes). "Our findings suggest that astrocytes are a pathway through which COVID-19 causes neurological damage," said Ricardo Costa, PhD, a postdoctoral fellow at the Louisiana State University (LSU) Health Shreveport and the study's first author. "This could explain many of the neurologic symptoms we see in COVID-19 patients, which include loss of sense of smell and taste, disorientation, psychosis, and stroke." Dr. Costa presented the team’s research on April 27 at the American Physiological Society annual meeting during the Experimental Biology (EB) 2021 meeting, held virtually April 27-30. The study is led by Diana Cruz-Topete, PhD, Assistant Professor of Molecular and Cellular Biology at LSU Health Shreveport, and includes collaborators Oscar Gomez-Torres, PhD, and Emma Burgos-Ramos, PhD, from the Universidad de Castilla-La Mancha in Spain. In the respiratory system, SARS-CoV-2 is known to infect a person's cells by grabbing hold of proteins on the cell surface called angiotensin-converting enzyme-2 (ACE2) receptors. It has been unclear whether brain cells have this receptor.

Capricor Therapeutics Signs Exclusive Worldwide License Agreement with Johns Hopkins University to Expand Company’s Exosome Platform Technology Portfolio

On April 29, 2021, Capricor Therapeutics (NASDAQ: CAPR), a biotechnology company focused on the development of transformative cell- and exosome-based therapeutics for the treatment and prevention of a broad spectrum of diseases, today announced that it has signed an exclusive, worldwide licensing agreement with Johns Hopkins University (JHU) to include engineered exosomes for vaccines and therapeutics as part of the Company’s exosome technology portfolio. "This exclusive license agreement with JHU allows Capricor to continue the expansion of our engineered exosome platform technology. We are focused on developing this platform to deliver nucleic acids or proteins effectively into cells and drive the expression of functional proteins,” said Linda Marbán, PhD, CEO, Capricor Therapeutics. “This agreement marks a significant milestone in the development of our Company. We believe that this new platform technology has the ability to expand into disease areas of high unmet medical need.” Under the terms of the agreement, Capricor has been granted the exclusive, worldwide rights to JHU’s co-owned interest in intellectual property described in the licensed patent applications, enabling Capricor to exclusively develop, manufacture and commercialize, with the right to sublicense, IP related to exosome technology for applications across both vaccine and therapeutic areas. Capricor is the co-owner of the intellectual property associated with the patent applications covered by the agreement. The licensed technology is based on extensive preclinical research conducted by Capricor and Stephen Gould, PhD, who serves as Capricor’s executive consultant. Dr.

Exosome-Based Approach Shows Potential for Treatment of Late-Stage Colorectal Cancer in Pre-Clinical Models

In a recent discovery by University of Minnesota (U of M) Medical School, researchers uncovered a new way to potentially target and treat late-stage colorectal cancer – a disease that kills more than 50,000 people each year in the United States. The team identified a novel mechanism by which colorectal cancer cells evade an anti-tumor immune response, which helped them develop an exosome-based therapeutic strategy to potentially treat the disease. “Late-stage colorectal cancer patients face enormous challenges with current treatment options. Most of the time, the patient’s immune system cannot efficiently fight against tumors, even with the help of the FDA-approved cancer immunotherapies,” said Subree Subramanian, PhD, an Associate Professor in the U of M Medical School’s Department of Surgery and a senior author of the study. In partnership with Xianda Zhao, MD, PhD, a postdoctoral fellow in Dr. Subramanian’s laboratory, the duo set out to investigate how colorectal cancer becomes resistant to available immunotherapies. What they found was recently published in Gastroenterology, including: (1) Colorectal cancer cells secrete exosomes that carry immunosuppressive microRNAs (miR-424) that actually prevent T cell and dendritic cell function because they block key proteins (CD28 and CD80) on these immune cell types, respectively. In the absence of these proteins, the T cells, which would normally kill the cancer cells, become ineffective and are eliminated from tumors, allowing tumors to grow. (2) By blocking these immunosuppressive microRNAs in cancer cells, the team observed an enhanced anti-tumor immune response and discovered that cancer cell-secreted exosomes also contain tumor-specific antigens that can stimulate the tumor-specific T cell response.

Massive Project to Read Genomes of All 70,000 Vertebrate Species Reports First Discoveries—Near-Complete, High-Quality Genomes of 25 Vertebrate Species—Cover Story of Nature

It's one of the most audacious projects in biology today--reading the entire genome of every bird, mammal, lizard, fish, and all other creatures with backbones, i.e., all vertebrates. And now comes the first major payoff from the Vertebrate Genome Project (VGP): near complete, high-quality genomes of 25 species, Howard Hughes Medical Institute (HHMI) Investigator Erich Jarvis, PhD, with scores of coauthors report April 28, 2021, in the journal Nature. The article serves as the cover story of the April 29, 2021 print issue of Nature (image). The sequenced species include the greater horseshoe bat, the Canada lynx, the platypus, and the kākāpō parrot (one of the first high-quality genomes of an endangered vertebrate species). The Nature paper also lays out the technical advances that let scientists achieve a new level of accuracy and completeness and paves the way for decoding the genomes of the roughly 70,000 vertebrate species living today, says HHMI Investigator and study coauthor David Haussler, PhD, a computational geneticist at the University of California, Santa Cruz (UCSC). "We will get a spectacular picture of how nature actually filled out all the ecosystems with this unbelievably diverse array of animals." The open-access Naure article was published online on April 28, 2021 and is titled “Towards Complete and Error-Free Genome Assemblies of All Vertebrate Species” (https://www.nature.com/articles/s41586-021-03451-0). Together with a slew of accompanying papers, the work is beginning to deliver on that promise. The project team has discovered previously unknown chromosomes in the zebra finch genome, for example, and a surprise finding about genetic differences between marmoset and human brains. The new research also offers hope for saving the kākāpō (photo) and the endangered vaquita dolphin from extinction.

Codiak to Present Preclinical Data Demonstrating Broad Potential Applications for Engineered Exosomes at American Society for Gene and Cell Therapy (ASGCT) Annual Meeting May 11-14

On April 27, 2021, Codiak BioSciences, Inc. (Nasdaq: CDAK), a clinical-stage biopharmaceutical company focused on pioneering the development of exosome-based therapeutics as a new class of medicines, announced that the company will present data from its engEx™ Platform at the 24th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT), which is being held virtually from May 11-14, 2021. Codiak scientists will present four abstracts detailing results from numerous preclinical studies evaluating the potential utility of engineered exosomes in multiple settings, including oncology, infectious disease, gene therapy, and neurology. “In addition to our current clinical programs that are testing engineered exosome therapeutic candidates in immuno-oncology, we see broad opportunity for our platform to create novel, targeted therapeutic approaches in multiple disease areas,” said Douglas E. Williams, PhD, President and Chief Executive Officer of Codiak. “The data to be presented at ASGCT highlights the power of the engEx platform to engineer specific features into exosomes for immune evasion, targeted cell tropism, and potent engagement of previously undruggable pathways, characteristics that serve as the foundation of a new class of medicines.”

CODIAK POSTER PRESENTATIONS--MAY 11, 2021; 8:00 A.M. – 10:00 A.M. EDT:

exoVACC™: A Novel Exosome-Based Vaccine Platform That Induces Robust, Tunable Cellular and Humoral Immune Responses in Animal Models
Abstract number: 721
Session: Immunological Aspects for Gene Therapy and Vaccines

Optimization of AAV Loading into Extracellular Vesicles As Method to Avoid Neutralizing Antibodies
Abstract number: 320
Session: AAV Vectors – Virology and Vectorology

Genome Sequencing Delivers Hope and Warning for Survival of Sumatran Rhinoceros

A study led by researchers at the Centre for Palaeogenetics in Stockholm shows that the last remaining populations of the Sumatran rhinoceros display surprisingly low levels of inbreeding. The researchers sequenced the genomes from 21 modern and historical rhinoceros' specimens, which enabled them to investigate the genetic health in rhinos living today, as well as a population that recently became extinct. These findings are published online on April 26, 2021 in Nature Communications. The open-access article is titled “Genomic Insights into the Conservation Status of the World’s Last Remaining Sumatran Rhinoceros Populations” (https://www.nature.com/articles/s41467-021-22386-8). With fewer than 100 individuals remaining, the Sumatran rhinoceros is one of the most endangered mammal species in the world. Recent reports of health issues and low fecundity have raised fears that the remaining populations are suffering from inbreeding problems. However, very little has been known about the genetic status of these enigmatic rhinos. To investigate whether the Sumatran rhinoceros is threatened by genetic factors, the researchers sequenced the genomes from 16 individuals representing the present-day populations on Borneo and Sumatra and the recently extinct population on the Malaysian Peninsula. This enabled them to estimate inbreeding levels, genetic variation, and the frequency of potentially harmful mutations in the populations. Moreover, by also sequencing the genomes from five historical samples, the researchers could investigate the genetic consequences of the severe population decline of the past 100 years. "To our surprise, we found relatively low inbreeding levels and high genetic diversity in the present-day populations on Borneo and Sumatra,” says Johanna von Seth, PhD student at the Centre for Palaeogenetics and co-lead author on the paper.

Four Free Weekly Virtual Talks on COVID-19 by World Leaders in Science; Talks Intended to Make COVID-19 Situation Clear to the Public; Series Titled “The Science from Infection to Treatment”--First Talk Today, April 28, 7 pm EDT

The Minor Memorial Library in Roxbury, Connecticut is excited to welcome four renowned scientists for a series of four lectures to explain the underlying science in producing antibodies, therapies, and vaccines to thwart the COVID-19 pandemic. The COVID-19 lectures will be given on Wednesdays: April 28, May 5, 12, and 19 at 7 pm EDT on Zoom. There is no charge for these programs, but registration is required. RSVP online at (https://www.minormemoriallibrary.org/?tribe_events=covid-101-your-immune...) to receive the Zoom link. Descriptions of the scheduled lectures follow. WEDNESDAY APRIL 28 AT 7 PM EDT ON ZOOM: LECTURE 1: “How Your Immune System Responds to Viral Infection” Vaccines have great potential to end the COVID-19 pandemic and yet are controversial. Hear from Marc Jenkins, PhD, about how vaccines stimulate the immune system and why vaccines are such powerful tools in infection control. Dr. Jenkins is a Regents and Distinguished McKnight University Professor and heads the Center for Immunology at the University of Minnesota. In 2020, he was elected to the National Academy of Sciences. WEDNESDAY MAY 5 AT 7 PM EDT ON ZOOM: LECTURE 2: “Antibody Therapy: What Is It and Is It Safe? Amidst the COVID-19 crisis, Regeneron utilized its suite of technologies to rapidly develop and release the first antibody cocktail with Emergency Use Authorization (EUA) to treat SARS-CoV-2 infection. Learn how the antibody therapy works through mimicking a natural immune response and why it continues to be potently active against all known variants. Lecturer Benjamin Fulton, PhD, is a Scientist in the Infectious Disease Department at Regeneron and a member of the team that developed Regeneron’s COVID-19 antibody cocktail.

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