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September 19th, 2017

PureTech Health Exclusively Licenses Novel Milk-Derived Exosome Technology for Oral Administration of Biologics, Nucleic Acids, and Complex Small Molecules

On September 19, 2017, PureTech Health plc (“PureTech Health” or the “Company”, LSE: PRTC), an advanced, clinical-stage biopharmaceutical company, announced an exclusive licensing agreement with 3P Biotechnologies, Inc., via University of Louisville, for an exosome-based technology (Calix) for the oral administration of biologics, nucleic acids, and complex small molecules. The Calix technology is based on the pioneering research of Ramesh Gupta, PhD, Founder of 3P Biotechnologies, Agnes Brown Duggan Chair in Oncological Research at the James Graham Brown Cancer Center, and Professor in the Department of Pharmacology and Toxicology at University of Louisville. This license, together with additional PureTech Health-generated intellectual property, establishes the company as a leader in the application of milk exosomes for the oral administration of therapeutic molecules. Exosomes, which can contain mixtures of lipids, proteins and nucleic acids, play a critical physiologic role in intercellular communication and the transport of macromolecules between cells and tissues. Mammalian-derived exosomes have attractive potential as vehicles for the administration of a variety of drug payloads, especially nucleic acids, because their natural composition will likely provide superior tolerability over the variety of synthetic polymers currently in use. Previously, exosomes had not been considered viable as vehicles for oral administration of drugs due to their lack of stability under the harsh physiologic conditions associated with transit through the stomach and small intestine. However, the milk-derived exosomes that form the basis for the Calix technology have evolved specifically to accomplish the task of oral transport of complex biological molecules.

Acoustic Microfluidic Device Can Gently and Rapidly Isolate Exosomes from Blood; Isolated Exosomes Can Be Analyzed for Molecular Signatures of Cancer and Other Diseases

Cells secrete nanoscale membraned packets called exosomes that can carry important messages from one part of the body to another. Scientists from MIT and other institutions have now devised a way to intercept these messages, which could be used to diagnose problems such as cancer or fetal abnormalities. Their new device uses a combination of microfluidics and sound waves to isolate these exosomes from blood. The researchers hope to incorporate this technology into a portable device that could analyze patient blood samples for rapid diagnosis, without involving the cumbersome and time-consuming ultracentrifugation method commonly used today. “These exosomes often contain specific molecules that are a signature of certain abnormalities. If you isolate them from blood, you can do biological analysis and see what they reveal,” says Dr. Ming Dao, a principal research scientist in MIT’s Department of Materials Science and Engineering and a senior author of the study, which appears in PNAS the week of September 18, 2017. The paper’s senior authors also include Dr. Subra Suresh, President-Designate of Nanyang Technological University in Singapore, MIT’s Vannevar Bush Professor of Engineering Emeritus, and a former Dean of Engineering at MIT; Dr. Tony Jun Huang, a Professor of Mechanical Engineering and Materials Science at Duke University; and Dr. Yoel Sadovsky, Director of the Magee-Women’s Research Institutein Pittsburgh. The paper’s lead author is Duke graduate student Mengxi Wu. The article is titled “Isolation of Exosomes from Whole Blood by Integrating Acoustics and Microfluidics. In 2014, the same team of researchers first reported that they could separate cells by exposing them to sound waves as they flowed through a tiny channel.

Rutgers Researchers Shed Light on Role of Key Fat-Regulating Enzyme in Human Health; Findings May Hold Clues to Obesity, Diabetes, Cancer, And Other Diseases

had already been known that the enzyme known as phosphatidic acid phosphatase plays a crucial role in regulating the amount of fat in the human body. Controlling it is therefore of interest in the fight against obesity. But scientists at Rutgers University-New Brunswick have now found that getting rid of the enzyme entirely can increase the risk of cancer, inflammation, and other ills. Their findings were published online on July 3, 2017 in the Journal of Biological Chemistry. "The goal of our lab is to understand how we can tweak and control this enzyme," said Dr. George M. Carman, Board of Governors Professor in the Department of Food Science in the School of Environmental and Biological Sciences. "For years, we have been trying to find out how to fine-tune the enzyme's activity so it's not too active, and creating too much fat, but it's active enough to keep the body healthy." The JBC article is titled “Yeast PAH1-Encoded Phosphatidate Phosphatase Controls The Expression of CHO1-Encoded Phosphatidylserine Synthase for Membrane Phospholipid Synthesis.” The enzyme was discovered in 1957 and Gil-Soo Han, Research Assistant Professor in the Rutgers Center for Lipid Research, discovered the gene encoding the enzyme in 2006. The enzyme determines whether the body's phosphatidic acid will be used to create storage fat, or to create the lipids in cell membranes. The current study used baker's yeast as a model organism, becausee it also contains the key enzyme. Dr. Han, study lead author, deleted a gene in yeast to eliminate the enzyme. That led to accumulations of phosphatidic acid, with cells making far more membrane lipids than necessary, said Dr. Carman, who founded the center in Rutgers' New Jersey Institute for Food, Nutrition, and Health a decade ago.

September 18th

New Lung Cell Type Identified; Finding May Lead to New, Non-Traditional Approaches to Treating Pneumonia and Chronic Lung Diseases

A recent study has identified a new lung cell type that is implicated in the body's innate immune defense against the bacteria Streptococcus pneumoniae--one of the leading causes of pneumonia worldwide. The findings, which were published online on September 18, 2017 in the Journal of Clinical Investigation, may lead to new, non-traditional approaches in the fight against pneumonia and chronic lung diseases. The article is titled “Expression of Piwi Protein MIWI2 Defines a Distinct Population of Multiciliated cells.” There are two classifications of cells in the human body: germ cells that are used to make sperm and eggs and somatic cells that make up every other cell in the body including lung cells. There are widespread differences between germ cells and somatic cells underscoring their markedly different roles in human biology. It was previously thought that the MIWI2 gene was only expressed in male germ cells as part of a family of genes that ensure the proper development of sperm. However, researchers at Boston University School of Medicine (BUSM) have discovered that, not only is the same gene expressed in somatic cells in the body, but it also marks a distinct population of multi-ciliated cells that line the upper airways of the lung. "These ciliated cells have hair-like projections that function to sweep mucus and other foreign material out of the lung. However, what sets this new population of ciliated cells apart is that they express the MIWI2 protein and in this report, were found to have a specialized role in controlling lung infection," explains corresponding author Matthew Jones, PhD, Assistant Professor of Medicine at BUSM.

BOOK REVIEW—"Ebola: The Natural and Human History of a Deadly Virus”

The objective of David Quammen’s book, “Ebola: The Natural and Human History of a Deadly Virus” (published October 20, 2014) is stated clearly in the introduction section as “to place the 2014 West Africa outbreak […] within a broader context that makes sense of those mysteries and their partial solutions. My offering here is merely a partial view of the history and science of Ebola” (Quammen, p. 2). Quammen then continues to explain that he did not have a traumatizing experience of losing his loved ones as many have, but did travel through “Ebola habitat” and became very close friends with two men who experienced the horrible realities of the Ebola virus. Quammen uses anecdotes to educate his readers regarding the Ebola virus and similar viruses, such as the Marburg virus for example. In the beginning of the book, Quammen tells about the outbreak in the village of Mayibout 2 in Gabon, Africa, where 18 people mysteriously acquired an illness and quickly died. The original victim had eaten a chimpanzee that was found dead and rotting in the forest, and was then prepared traditionally to eat. Because chimps suffer from the virus and die quickly, as do humans infected with Ebola virus, neither we nor the chimps are the reservoir host. Finding the reservoir host is a great interest of many scientists and public health officials around the world. Another strategy Quammen used to explain the Ebola virus outbreak was comparing it with outbreaks of the Marburg virus, which causes a very similar disease that was recognized about nine years before Ebola. Both viruses are filamentous, lethal RNA viruses and appeared “twisty” to scientists in the labs. Ebola virus had many outbreaks throughout the years starting in 1976. Many research experiments were conducted, most of which were unsuccessful, attempting to isolate the Ebola virus.

Dogs’ Social Skills Linked to Oxytocin Sensitivity

The tendency of dogs to seek contact with their owners is associated with genetic variations in sensitivity for the hormone oxytocin, according to a new study from Linköping University, Sweden. The results have been published in Hormones and Behavior and contribute to our knowledge of how dogs have changed during their development from wolf to household pet. The article is titled “Intranasal Oxytocin and a Polymorphism in the Oxytocin Receptor Gene Are Associated with Human-Directed Social Behavior in Golden Retriever Dogs.” During their domestication from their wild ancestor the wolf to the pets we have today, dogs have developed a unique ability to work together with humans. One aspect of this is their willingness to “ask for help” when faced with a problem that seems to be too difficult. There are, however, large differences between breeds, and between dogs of the same breed. A research group in Linköping, led by Professor Per Jensen, has discovered a possible explanation of why dogs differ in their willingness to collaborate with humans. The researchers suspected that the hormone oxytocin was involved. It is well-known that oxytocin plays a role in social relationships between individuals, in both humans and animals. The effect of oxytocin depends on the function of the structure that it binds to, the receptor, in the cell. Previous studies have suggested, among other things, that differences in dogs’ ability to communicate are associated with variations in the genetic material located close to the gene that codes for the oxytocin receptor. The researchers in the present study examined 60 golden retrievers as they attempted to solve a previously insoluble problem. “The first step was to teach the dogs to open a lid, and in this way, get hold of a treat.

September 15th

Aethlon Medical Is Awarded $300K NCI Government Contract to Develop Device Strategy for Isolating Oncosomes and Non-Malignant Exosomes

Aethlon Medical, Inc. (Nasdaq: AEMD), a therapeutic technology company focused on unmet needs in global health and biodefense, announced, on September 14, 2017, that the National Cancer Institute (NCI) has awarded the Company a government contract (number HHSN261201700022C). The title of this SBIR Topic 359 Phase I contract is "Device Strategy for Selective Isolation of Oncosomes and Non-Malignant Exosomes." The NCI Phase I contract period runs from September 15, 2017 and runs through June 14, 2018. The total amount of the firm fixed price contract is $299,250. The contract calls for two subcontractors to work with the Company. The subcontractors under Aethlon Medical on the contract are University of Pittsburgh and Massachusetts General Hospital. Aethlon Medical is investigating the potential use of the Aethlon Hemopurifier® to reduce the presence of circulating tumor-derived exosomes (oncosomes), which contribute to cancer progression. The Hemopurifier® is currently being advanced to treat life-threatening viral infections under an FDA designated Expedited Access Pathway (EAP) program. The Company is also engaged in the advancement of exosomal biomarkers to diagnose and monitor cancer and other disease conditions. Aethlon Medical is focused on addressing unmet needs in global health and biodefense. The Aethlon Hemopurifier® was designed to reduce the presence of life-threatening viral pathogens from the circulatory system of infected individuals. The technology provides a first-line candidate defense against viruses that are not addressed with approved therapies, including a broad-spectrum of naturally occurring pandemic threats and agents of bioterrorism.

Evidence for Lack of Anti-Viral Argonaute2 Proteins in Vertebrates

Insects and plants have an important ancient defense mechanism that helps them to fight viruses. This is encoded in their DNA. Scientists have long assumed that vertebrates - including humans - also had this same mechanism. But researchers at KU Leuven (University of Leuven), Belgium, have found that vertebrates have lost this particular asset in the course of their evolution. The possibilities encoded in our DNA are expressed via RNA. Conversely, RNA interference (RNAi) can also suppress the expression of a specific gene. Insects and plants use this RNAi mechanism to defend themselves against viruses, among other things. With a little help, insects and plants can even be made resistant to certain diseases through this RNAi mechanism. Examples include so-called genetically modified crops. It seems only logical to assume, then, that humans can be protected against specific diseases in a similar way. However, past experiments to this effect have proven to be a challenge. Researchers from the Animal Physiology and Neurobiology unit at KU Leuven have now shown why this is the case. The research was published online on August 23, 2017 in Scientific Reports. The open-access article is titled “The Evolution of Animal Argonautes: Evidence for the Absence of Antiviral AGO Argonautes in Vertebrates.” KU Leuven researcher Dr. Niels Wynant studied Argonaute proteins, which play an important role in the RNAi process. "In a first stage, we compared the DNA of more than 40 living organisms from various important animal groups. It's the first time that such a diverse group was studied. It didn't take us long to find the Argonaute proteins in these organisms. We also discovered the existence of three distinct types of Argonautes, each with a specific biological role," Dr. Wynant explains.

$11.6 Million NIH Grant Will Finance Studies of Possible Role of Exosomes in Heart Repair and Regeneration

The incidence of heart disease is on the rise, and new therapeutic strategies are needed. Approaches based on stem cells, which can potentially preserve or even regenerate heart muscle cells damaged by ischemia - a hallmark of heart disease - are especially promising. Now, thanks to an $11.6-Million Program Project Grant (PPG) from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) under award number P01HL134608, scientists at the Lewis Katz School of Medicine at Temple University (LKSOM) are poised to explore new possibilities in stem-cell-based treatments for heart repair and regeneration. According to a release dated September 13, 2017, the project is aimed specifically at better understanding the regenerative capabilities of stem-cell-derived microvesicles known as exosomes. The Principal Investigator on the new award is Raj Kishore, PhD, Professor of Pharmacology and Medicine and Director of the Stem Cell Therapy Program in the Center for Translational Medicine at LKSOM. According to Dr. Kishore, exosomes offer an exciting opportunity to develop a cell-free approach to stem cell-based therapy for heart disease. "Previous attempts at stem cell therapy for heart disease did not work as hoped," Dr. Kishore said. "In many cases, the stem cells themselves were injured by inflammation in the heart following injection or were not functioning optimally, having been weakened from disease, such as diabetes, or age." Exosomes differ from stem cells in that they are not actually cells. Rather, they are tiny packages, roughly 50-150 nanometers in diameter, which are secreted by stem cells and taken up by neighboring tissue cells. They can carry stem cell-specific small RNAs, proteins, and other cargo that mimic stem cell functions once released inside cells, giving them beneficial properties.

September 14th

Study Highlights Possible Key Role of TOMM40 Gene Variant in Alzheimer’s Disease

The notorious genetic marker of Alzheimer's disease and other forms of dementia, ApoE4, may not be a lone wolf. Researchers from the University of Southern California (USC) and the University of Manchester have found that another gene, TOMM40 (image depicts TOMM40 protein), complicates the picture. Although ApoE4 plays a greater role in some types of aging-related memory ability, TOMM40 may pose an even greater risk for other types. TOMM40 and APOE genes are neighbors, adjacent to each other on chromosome 19, and they are sometimes used as proxies for one another in genetic studies. At times, scientific research has focused chiefly on one APOE variant, ApoE4, as the No. 1 suspect behind Alzheimer's and dementia-related memory decline. The literature also considers the more common variant of APOE, ApoE3, neutral in risk for Alzheimer's disease. USC researchers believe their new findings raise a significant research question: Has TOMM40 been misunderstood as a sidekick to ApoE4 when it is really a mastermind, particularly when ApoE3 is present? "Typically, ApoE4 has been considered the strongest known genetic risk factor for cognitive decline, memory decline, Alzheimer's disease, or dementia-related onset," said Dr. T. Em Arpawong, the study's lead author and a post-doctoral fellow in the USC Dornsife College of Letters, Arts and Sciences Department of Psychology. "Although prior studies have found some variants of this other gene TOMM40 may heighten the risk for Alzheimer's disease, our study found that a TOMM40 variant was actually more influential than ApoE4 on the decline in immediate memory - the ability to hold onto new information." Studies have shown that the influence of genes associated with memory and cognitive decline intensifies with age.