Syndicate content

RoosterBio and Exopharm Partner to Bring High-Grade Therapeutic Extracellular Vesicles/Exosomes into Clinical Practice

On August 7, 2017, RoosterBio, Inc. and Exopharm Pty Ltd announced a formal heads of agreement under which they will work together on a Stem Cell Exomere Program, aimed at bringing high-grade therapeutic extracellular vesicles/exosomes derived from adult stem cells into clinical practice. Exosomes secreted by stem cells are a new class of therapeutic product well suited to be used in regenerative medicine (“RM”) applications, but large-scale stem cell manufacturing bottlenecks impede broad clinical use of these natural bioactive nanoparticles. RoosterBio, based in Frederick, Maryland, USA, has strengths in human mesenchymal stem/stromal cells (hMSC) technology-based process and product design innovation, and develops commercially-viable biomanufacturing processes that support both upstream processing (USP) and downstream processing (DSP), offered as “acceleration services” to customers. Exopharm is a Melbourne, Australia-based biotechnology company specializing in its patent-applied-for LEAP isolation technology, Exomere manufacturing and clinical development, and commercialization of its Exomere technology. Exomeres are a pharma-grade fraction of cell-derived bilayer lipid membrane extracellular vesicles in a size range of around 40-200 nm purified using Exopharm’s LEAP ligand technology. Recent small-scale human studies have demonstrated that purified extracellular vesicles/exosomes derived from adult stem cells are safe and effective – yet there is no accepted and standardized commercial-scale manufacturing process for these submicroscopic particles. RoosterBio and Exopharm have complementary technologies, competencies, and commercial objectives – were proud to announce the establishment of their joint Stem Cell Exomere Program.

BMAL1 Protein in Muscle, Not Brain, Regulates Sleep in Mice

Scientists exploring the brain for answers to certain sleep disorders may have been looking in the wrong place. A new study shows that a protein in muscle can lessen the effects of sleep loss in mice, a surprising revelation that challenges the widely accepted notion that the brain controls all aspects of sleep. The new finding – the result of a collaboration between the University of Texas (UT) Southwestern’s Peter O’Donnell Jr. Brain Institute and two other medical centers – gives scientists a new target besides the brain to develop therapies for people with excessive sleepiness. “This finding is completely unexpected and changes the ways we think sleep is controlled,” said Dr. Joseph S. Takahashi (photo), Chairman of Neuroscience at UT Southwestern Medical Center and Investigator with the Howard Hughes Medical Institute. The research published online on July 20, 2017 in eLife demonstrates how a circadian clock protein (BMAL1) in the muscle regulates the length and manner of sleep. The article is titled “Bmal1 function in skeletal muscle regulates sleep.” While the protein’s presence or absence in the brain had little effect on sleep recovery, mice with higher levels of BMAL1 in their muscles recovered from sleep deprivation more quickly. In addition, removing BMAL1 from the muscle severely disrupted normal sleep, leading to an increased need for sleep, deeper sleep, and a reduced ability to recover. Dr. Takahashi said the finding may eventually lead to therapies that could benefit people in occupations requiring long stretches of wakefulness, from military to airline piloting. “These studies show that factors in muscles can signal to the brain to influence sleep. If similar pathways exist in people, this would provide new drug targets for the treatment of sleep disorders,” said Dr.

Yale Scientists Reveal Role for Lysosome Transport in Alzheimer's Disease Progression; Finding Suggests Possible New Therapeutic Approaches

Researchers from the Yale University School of Medicine have discovered that defects in the transport of lysosomes within neurons promote the buildup of protein aggregates in the brains of mice with Alzheimer's disease. The study, which was published on August 7, 201 in The Journal of Cell Biology (JCB), suggests that developing ways to restore lysosome transport could represent a new therapeutic approach to treating the neurodegenerative disorder. The open-access article is titled “Impaired JIP3-Dependent Axonal Lysosome Transport Promotes Amyloid Plaque Pathology.” Alzheimer's disease is the sixth leading cause of death in the United States, with over 5 million Americans currently estimated to be living with the disorder. A characteristic feature of the disease is the formation of amyloid plaques inside the brain. The plaques consist of extracellular aggregates of a toxic protein fragment called β-amyloid surrounded by numerous swollen axons, the parts of neurons that conduct electric impulses to other nerve cells. These axonal swellings are packed with lysosomes, cellular garbage disposal units that degrade old or damaged components of the cell. In neurons, lysosomes are thought to "mature" as they are transported from the ends of axons to the neuronal cell body, gradually acquiring the ability to degrade their cargo. The lysosomes that get stuck and accumulate inside the axonal swellings associated with amyloid plaques fail to properly mature, but how these lysosomes contribute to the development of Alzheimer's disease is unclear. One possibility is that they promote the buildup of β-amyloid because some of the enzymes that generate β-amyloid by cleaving a protein called amyloid precursor protein (APP) accumulate in the swellings with the immature lysosomes.

Scientists Create Potential Stem Cell Therapy for Lung Fibrosis Conditions, Including Idiopathic Pulmonary Fibrosis (IPF)

A team of scientists from the University of North Carolina (UNC) School of Medicine and North Carolina State University (NCSU) has developed promising research towards a possible stem cell treatment for several lung conditions, such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and cystic fibrosis -- often-fatal conditions that affect tens of millions of Americans. In the journal Respiratory Research, the scientists demonstrated that they could harvest lung stem cells from people using a relatively non-invasive, doctor's-office technique. They were then able to multiply the harvested lung cells in the lab to yield enough cells sufficient for human therapy. Thus open-access article, published online on June 30, 2017, is titled “Derivation of Therapeutic Lung Spheroid Cells from Minimally Invasive Transbronchial Pulmonary Biopsies.” In a second study, published in Stem Cells Translational Medicine, the team showed that in rodents they could use the same type of lung cell to successfully treat a model of IPF - a chronic, irreversible, and ultimately fatal disease characterized by a progressive decline in lung function. The open-access article, published online on August 7, 2017, is titled “Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis.” The researchers have been in discussions with the FDA and are preparing an application for an initial clinical trial in patients with IPF. "This is the first time anyone has generated potentially therapeutic lung stem cells from minimally invasive biopsy specimens," said co-senior author of both papers Jason Lobo, MD, an Assistant Professor of Medicine at UNC and Medical Director of Lung Transplant and Interstitial Lung Disease.

Using CRISPR and Skin Grafts, Researchers Boost Insulin Levels to Correct Diet-Induced Obesity and Diabetes in Mice; Gene Therapy Via Skin Could Treat Many Diseases, Scientists Suggest

A research team based at the University of Chicago has overcome challenges that have limited gene therapy and demonstrated how their novel approach with skin transplantation could enable a wide range of gene-based therapies to treat many human diseases. In the August 3, 2017 issue of Cell Stem Cell, the researchers provide "proof-of-concept." They describe a new form of gene-therapy - administered through skin transplants - to treat two related and extremely common human ailments: type-2 diabetes and obesity. "We resolved some technical hurdles and designed a mouse-to-mouse skin transplantation model in animals with intact immune systems," said study author Xiaoyang Wu, PhD, Assistant Professor in the Ben May Department for Cancer Research at the University of Chicago. "We think this platform has the potential to lead to safe and durable gene therapy, in mice and we hope, someday, in humans, using selected and modified cells from skin." Beginning in the 1970s, physicians learned how to harvest skin stem cells from a patient with extensive burn wounds, grow them in the laboratory, then apply the lab-grown tissue to close and protect a patient's wounds. This approach is now standard. However, the application of skin transplants is better developed in humans than in mice. "The mouse system is less mature," Dr. Wu said. "It took us a few years to optimize our 3D skin organoid culture system." This study, entitled "Engineered Epidermal Progenitor Cells Can Correct Diet-Induced Obesity and Diabetes," is the first to show that an engineered skin graft can survive long term in wild-type mice with intact immune systems. "We have a better than 80 percent success rate with skin transplantation," Dr. Wu said. "This is exciting for us." The article is open-access.

Exosome Diagnostics Achieves ISO 13485 Certification Its USA and Germany Facilities; Company Growing into IVD Manufacturer Due to Demand for Its Instrument Platform & Companion Diagnostic Tests

On August 3, 2017, Exosome Diagnostics, Inc., a leader in the liquid biopsy market, announced that it has received ISO 13485 certification for both its USA and Germany facilities. This achievement paves the way for the company to be an In Vitro Diagnostic (IVD) medical device design and manufacturing organization. Combined with the company’s CLIA-certified Waltham, Massachusetts laboratory and ISO 15189-accredited Munich laboratory, the IVD-certified locations will serve as an integral part of the company’s strategy for the instrument platform, companion diagnostics, and diagnostics to better the lives of patients worldwide. The British Standards Institution (BSI) has certified Exosome Diagnostics under ISO 13485:2003 under CMDCAS for the following scope: “Design, development, manufacture, distribution, installation, and service of In Vitro Diagnostic (IVD) medical devices including opto-electromechanical instruments, sample collection kits, reagents, and disposables.” As defined by the International Organization for Standardization, ISO 13485 is a standard that specifies requirements for a quality management system (QMS) where an organization needs to demonstrate its ability to provide medical devices (IVDs) and related services that consistently meet customer needs and applicable regulatory requirements. “This ISO 13485 certification is a testament to the compliance initiatives undertaken by Exosome Dx to design and manufacture IVDs. Working closely with the notified body and appropriate regulatory agencies, Exosome Dx adheres to the strictest standards to provide the highest quality of products to clinicians,” stated Raaj Venkatesan, Head of Regulatory Affairs at Exosome Diagnostics.

“The Biology of Color”—New Study Explores Advances and Challenges in Field of Animal Coloration

Scientists are on a threshold of a new era of color science due largely to an explosion of technologies, but key questions remain for the field, according to a study published in the August 4, 2017 issue of Science by an international team of researchers led by Dr. Tim Caro of the University of California (UC), Davis. While studies have long used color as a factor for understanding evolution, only recently have visual physiologists, sensory and behavioral ecologists, evolutionary biologists, and anthropologists come together to study how color is produced and perceived by animals and its function and patterns of evolution. With this wide-ranging synthesis in Science, entitled "The Biology of Color," such a multidisciplinary group provides a roadmap of advances in the field of animal coloration, as well as citing remaining challenges. "In the past 20 years, the field of animal coloration research has been propelled forward very rapidly by technological advances," said corresponding author Dr. Caro, a professor in the UC Davis Department of Wildlife, Fish and Conservation Biology. "These include digital imaging, innovative laboratory and field studies, and large-scale comparative analyses, each of which is allowing completely new questions to be asked." Coloration is a complicated biological trait. Animals use it for camouflage, to send warning signals, attract mates, send social signals, regulate their body temperature, and thwart pests, among other uses. Dr. Caro's own research has helped clarify long-held mysteries about animal coloration. This includes why zebras have black and white stripes (to avoid biting flies) (https://www.ucdavis.edu/news/wildlife-biologist-earns-his-zebra-stripes-...) and why pandas are black and white (to provide camouflage in both snow and dark forests, because they need to eat year-round).

Germline Gene Correction for Inherited Genetic Disease Demonstrated in Human Embryos

Scientists have demonstrated an effective way of using a gene-editing tool to correct a disease-causing gene mutation in human embryos and stop it from passing to future generations. The new technique uses the gene-editing tool CRISPR to target a mutation in nuclear DNA that causes hypertrophic cardiomyopathy, a common genetic heart disease that can cause sudden cardiac death and heart failure. The research, published online on August 2, 2017 in Nature, demonstrates a new method of repairing a disease-causing mutation and preventing it from being inherited by succeeding generations. The article is titled “Correction of a Gene Mutation in Human Embryos.” This is the first time that scientists have successfully tested the method on donated clinical-quality human eggs. “Every generation on would carry this repair because we’ve removed the disease-causing gene variant from that family’s lineage,” said senior author Shoukhrat Mitalipov, PhD, who directs the Center for Embryonic Cell and Gene Therapy at Oregon Health and Sciences University (OHSU) in Portland, Oregon. “By using this technique, it’s possible to reduce the burden of this heritable disease on the family and eventually the human population.” The study provides new insight into a technique that could apply to thousands of inherited genetic disorders affecting millions of people worldwide. The gene-editing technique described in this study, done in concert with in vitro fertilization, could provide a new avenue for people with known heritable disease-causing genetic mutations to eliminate the risk of passing the disease to their children. It could also increase the success of IVF by increasing the number of healthy embryos.

Mysterious Children’s Neurological Disease Traced to Single Base Error in One Gene; Deep Sequencing Is Key to Discovery of Mutation Affecting Ribosomal RNA Metabolism

In a new study published on August 3, 2017 in The American Journal of Human Genetics, a multinational team of researchers describes, for the first time, the biological basis of a severe neurological disorder in children. The extremely rare disorder is characterized by developmental regression and neurodegeneration. At first, the children lead normal lives and seem identical to their age-matched peers. However, beginning at around 3 to 6 years of age, the children present with neurological deterioration, gradually losing motor, cognitive, and speech functions. Although the condition progresses slowly, most patients are completely dependent on their caretakers by 15-20 years of age. Researchers from the Hadassah Medical Center and the Hebrew University of Jerusalem’s Faculty of Medicine, working with colleagues from the Pennsylvania State University College of Medicine and a multinational research team, have now identified and studied seven children — from Canada, France, Israel, Russia, and the United States — who suffer from the disorder. The researchers found in all patients the same spontaneously occurring, non-inherited genetic change in a gene (named “UBTF”) responsible for ribosomal RNA formation. Because of this small change, the patients’ cells are flooded with ribosomal RNA and are poisoned by it. (Ribosomes are responsible for the translation and production of cell proteins; themselves, they are made up of ribosomal proteins and of ribosomal RNA in a precise ratio). The researchers found an identical error in the same gene in all the patients tested, representing a difference of one letter among the roughly 3 billion letters that make up human DNA.

Autism May Reflect Excitation-Inhibition Imbalance in Brain, Stanford Study Finds

A study by Stanford University investigators suggests that key features of autism reflect an imbalance in signaling from excitatory and inhibitory neurons in a portion of the forebrain, and that reversing the imbalance could alleviate some of its hallmark symptoms. In a series of experiments conducted on a mouse model of the disorder, the scientists showed that reducing the ratio of excitatory to inhibitory signaling countered hyperactivity and deficits in social ability, two classic symptoms of autism in humans. The study was published in the August 2, 2017 issue of Science Translational Medicine. Dr. Karl Deisseroth, Professor of Bioengineering and of Psychiatry and Behavioral Sciences, is the study's senior author. The lead author is former graduate student Aslihan Selimbeyoglu, PhD. The article is titled “Modulation of Prefrontal Cortex Excitation/Inhibition Balance Rescues Social Behavior In CNTNAP2-Deficient Mice.” In 2011, Dr. Deisseroth's group published a study in Nature showing that autism-like behavioral deficits could be induced in ordinary mice by elevating the ratio of excitatory to inhibitory neuronal firing patterns in the mice's medial prefrontal cortex. The new study shows that decreasing that ratio restores normal behavior patterns in a strain of lab mice bioengineered to mimic human autism. These mice carry a mutation equivalent to a corresponding mutation in humans that is associated with autism spectrum disorder. For reasons that are not understood, the incidence of autism spectrum disorder has increased steadily in recent years, said Dr. Deisseroth, a practicing psychiatrist. Approximately 1 in 80 American children may be diagnosed with the disorder, which is characterized by repetitive behaviors and difficulty with social interaction.

Syndicate content